Murali, K. & Banerjee, S.
(2019). Let’s address burnout in oncologists and reimagine the way we work. Nature reviews clinical oncology,
Castellani, F., Nganga, E.C., Dumas, L., Banerjee, S. & Rockall, A.G.
(2019). Imaging in the pre-operative staging of ovarian cancer. Abdominal radiology,
(2019). Reply to ‘Physician burnout: let’s avoid unsubstantiated claims’. Nature reviews clinical oncology,
Liposits, G., Loh, K.P., Soto-Perez-de-Celis, E., Dumas, L., Battisti, N.M., Kadambi, S., Baldini, C., Banerjee, S. & Lichtman, S.M.
(2019). PARP inhibitors in older patients with ovarian and breast cancer: Young International Society of Geriatric Oncology review paper. Journal of geriatric oncology,
Fabbro, M., Moore, K.N., Dørum, A., Tinker, A.V., Mahner, S., Bover, I., Banerjee, S., Tognon, G., Goffin, F., Shapira-Frommer, R., et al.
(2019). Efficacy and safety of niraparib as maintenance treatment in older patients (≥ 70 years) with recurrent ovarian cancer: Results from the ENGOT-OV16/NOVA trial. Gynecologic oncology,
Khalique, S., Lord, C.J., Banerjee, S. & Natrajan, R.
(2019). Translational genomics of ovarian clear cell carcinoma. Seminars in cancer biology,
Banerjee, S., Oza, A.M., Birrer, M.J., Hamilton, E.P., Hasan, J., Leary, A., Moore, K.N., Mackowiak-Matejczyk, B., Pikiel, J., Ray-Coquard, I., et al.
(2018). Anti-NaPi2b antibody–drug conjugate lifastuzumab vedotin (DNIB0600A) compared with pegylated liposomal doxorubicin in patients with platinum-resistant ovarian cancer in a randomized, open-label, phase II study. Annals of oncology,
Prager, G.W., Braga, S., Bystricky, B., Qvortrup, C., Criscitiello, C., Esin, E., Sonke, G.S., Martínez, G.A., Frenel, J.-., Karamouzis, M., et al.
(2018). Global cancer control: responding to the growing burden, rising costs and inequalities in access. Esmo open,
Stewart, J., George, A. & Banerjee, S.
(2018). Olaparib for the treatment of relapsed ovarian cancer with a BRCA1/2 mutation. Expert review of anticancer therapy,
Oza, A., Kaye, S., Van Tornout, J., Sessa, C., Gore, M., Naumann, R.W., Hirte, H., Colombo, N., Chen, J., Gorla, S., et al.
(2018). Phase 2 study evaluating intermittent and continuous linsitinib and weekly paclitaxel in patients with recurrent platinum resistant ovarian epithelial cancer. Gynecologic oncology,
Moore, K.N., Vergote, I., Oaknin, A., Colombo, N., Banerjee, S., Oza, A., Pautier, P., Malek, K. & Birrer, M.J.
(2018). FORWARD I: a Phase III study of mirvetuximab soravtansine versus chemotherapy in platinum-resistant ovarian cancer. Future oncology,
Khalique, S., Naidoo, K., Attygalle, A.D., Kriplani, D., Daley, F., Lowe, A., Campbell, J., Jones, T., Hubank, M., Fenwick, K., et al.
(2018). Optimised ARID1A immunohistochemistry is an accurate predictor ofARID1Amutational status in gynaecological cancers. The journal of pathology: clinical research,
Murali, K. & Banerjee, S.
(2018). Burnout in oncologists is a serious issue: What can we do about it?. Cancer treatment reviews,
Oza, A.M., Matulonis, U.A., Malander, S., Hudgens, S., Sehouli, J., del Campo, J.M., Berton-Rigaud, D., Banerjee, S., Scambia, G., Berek, J.S., et al.
(2018). Quality of life in patients with recurrent ovarian cancer treated with niraparib versus placebo (ENGOT-OV16/NOVA): results from a double-blind, phase 3, randomised controlled trial. The lancet oncology,
Banerjee, S., Dafni, U., Allen, T., Arnold, D., Curigliano, G., Garralda, E., Garassino, M.C., Haanen, J., Hofstädter-Thalmann, E., Robert, C., et al.
(2018). Gender-related challenges facing oncologists: the results of the ESMO Women for Oncology Committee survey. Esmo open,
Although women account for a growing proportion of the oncology workforce, there is evidence they are under-represented in leadership roles. To gain further insights into this issue and extend understanding of gender challenges, the European Society for Medical Oncology Women for Oncology (W4O) Committee undertook a survey of female and male oncologists in 2016.Design
The 2016 W4O questionnaire included questions on (1) Demographics and professional environment, (2) Gender impact on career development, (3) Challenges for career progression and inappropriate behaviour experienced in the workplace, (4) Barriers for gender parity and (5) The gender gap. Between July and September 2016, the online survey was available to male and female clinical and academic oncology healthcare professionals in the EU and internationally.Results
Responses were analysed from 462 oncologists, of whom 76.7 % were women. Of female respondents, 45.5 % had a managerial or leadership role, compared with 65 % of male respondents (p<0.001). Men were more likely to have leadership roles, even in clinical teams with more women than men. Women respondents were more likely to consider their gender had a major impact on their career than men: 35.9 % vs 20.9 % (p<0.001). The biggest challenge to career progression for women was work and family balance (64.2%). Of female respondents, 14.4 % believed there had been significant or major progress in closing the gender pay gap compared with 39.3 % of men (p<0.001). Of female participants, 37.7 % reported they had encountered unwanted sexual comments by a superior or colleague.Conclusions
New initiatives are needed to address under-representation of women oncologists in leadership roles, including greater and concrete promotion of work–life balance, development and leadership training for women, and more support for flexible working. The fact that over a third of women in the survey had encountered unwanted sexual comments at work is of great concern and must be urgently addressed..
Hofstädter-Thalmann, E., Dafni, U., Allen, T., Arnold, D., Banerjee, S., Curigliano, G., Garralda, E., Garassino, M.C., Haanen, J., Robert, C., et al.
(2018). Report on the status of women occupying leadership roles in oncology. Esmo open,
While the global workforce is approaching gender parity, women occupy a small number of management level positions across most professions, including healthcare. Although the inclusion of women into the membership of many oncology societies has increased, the under-representation of women in leadership roles within international and national oncology societies remains relatively consistent. Moreover, the exact status of women participating as board members or presidents of oncology societies or as speakers at oncology congresses was undocumented to date.Methods
The database used in this analysis was derived from data collection performed by the European Society for Medical Oncology for the years 2015–2016 and data analyses performed using the Statistical Analysis Software V.9.3 and R language for statistical computing V.3.4.0 by Frontier Science Foundation-Hellas. The literature search was performed by the authors.Results
We report the presence of a gender gap within oncology. Results regarding the under-representation of women occupying leadership roles in oncology show female participation as members of the board or presidents of national and international oncology societies and as invited speakers at oncology congresses remains below 50% in the majority of societies included in this analysis. Women in leadership positions of societies was associated with a higher percentage of female invited speakers at these societies’ congresses (p=0.006).Conclusion
The full contribution that can be attained from using the potential of women in leadership roles is currently under-realised. Examples of how gender and minority participation in organisations improves outcomes and creativity are provided from science, clinical practice and industry that show outcomes are greatly improved by collective participation of both men and women. Although there are programmes in place in many oncology organisations to improve this disparity, the gender gap is still there. Ongoing discussion may help to create more awareness in the effort to accelerate the advancement of women within oncology..
Orbegoso, C., Murali, K. & Banerjee, S.
(2018). The current status of immunotherapy for cervical cancer. Reports of practical oncology & radiotherapy,
Heindl, A., Khan, A.M., Rodrigues, D.N., Eason, K., Sadanandam, A., Orbegoso, C., Punta, M., Sottoriva, A., Lise, S., Banerjee, S., et al.
(2018). Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity. Nature communications,
Basu, B., Krebs, M.G., Sundar, R., Wilson, R.H., Spicer, J., Jones, R., Brada, M., Talbot, D.C., Steele, N., Ingles Garces, A.H., et al.
(2018). Vistusertib (dual m-TORC1/2 inhibitor) in combination with paclitaxel in patients with high grade serous ovarian and squamous non-small cell lung cancer. Ann oncol,
Background: We have previously shown that raised p-S6K levels correlate with resistance to chemotherapy in ovarian cancer. We hypothesised that inhibiting p-S6K signalling with the dual m-TORC1/2 inhibitor in patients receiving weekly paclitaxel could improve outcomes in such patients. Patients and Methods: In dose escalation, weekly paclitaxel (80 mg/m2) was given 6/7 weeks in combination with two intermittent schedules of vistusertib (dosing starting on the day of paclitaxel): schedule A, vistusertib dosed bd for 3 consecutive days per week (3/7days) and schedule B, vistusertib dosed bd for 2 consecutive days per week (2/7days). After establishing a recommended phase II dose (RP2D), expansion cohorts in high-grade serous ovarian cancer (HGSOC) and squamous non-small cell lung cancer (sqNSCLC) were explored in 25 and 40 patients, respectively. Results: The dose escalation arms comprised 22 patients with advanced solid tumours. The dose-limiting toxicities were fatigue and mucositis in schedule A and rash in schedule B. Based on toxicity, pharmacokinetic (PK) and pharmacodynamic (PD) evaluations, the RP2D was established as 80 mg/m2 paclitaxel with 50 mg vistusertib bd 3/7 days for 6/7 weeks. In the HGSOC expansion RECIST and GCIG CA125 response rates were 13/25 (52%) and 16/25 (64%), respectively with median progression-free survival (mPFS) of 5.8 months (95% CI: 3.28 - 18.54). The RP2D was not well tolerated in the SqNSCLC expansion, but toxicities were manageable after the daily vistusertib dose was reduced to 25 mg bd for the following 23 patients. The RECIST response rate in this group was 8/23 (35%) and the mPFS was 5.8 months (95% CI: 2.76 - 21.25). Discussion: In this phase I trial we report a highly active and well tolerated combination of vistusertib, administered as an intermittent schedule with weekly paclitaxel, in patients with HGSOC and SqNSCLC. Clinical trial registration: ClinicialTrials.gov identifier: CNCT02193633..
Murali, K., Makker, V., Lynch, J. & Banerjee, S.
(2018). From Burnout to Resilience: An Update for Oncologists. American society of clinical oncology educational book,
Moore, K., Colombo, N., Scambia, G., Kim, B.-., Oaknin, A., Friedlander, M., Lisyanskaya, A., Floquet, A., Leary, A., Sonke, G.S., et al.
(2018). Maintenance Olaparib in Patients with Newly Diagnosed Advanced Ovarian Cancer. New england journal of medicine,
Banerjee, S., Califano, R., Corral, J., de Azambuja, E., De Mattos-Arruda, L., Guarneri, V., Hutka, M., Jordan, K., Martinelli, E., Mountzios, G., et al.
(2017). Professional burnout in European young oncologists: results of the European Society for Medical Oncology (ESMO) Young Oncologists Committee Burnout Survey. Annals of oncology,
Banerjee, S., Preusser, M., Tabernero, J. & Strijbos, M.
(2017). Reply to the letter to the editor ‘Can we trust burnout research?’ by Bianchi et al. Annals of oncology,
Khalique, S. & Banerjee, S.
(2017). Nintedanib in ovarian cancer. Expert opinion on investigational drugs,
McLachlan, J., Boussios, S., Okines, A., Glaessgen, D., Bodlar, S., Kalaitzaki, R., Taylor, A., Lalondrelle, S., Gore, M., Kaye, S., et al.
(2017). The Impact of Systemic Therapy Beyond First-line Treatment for Advanced Cervical Cancer. Clinical oncology,
George, A., Banerjee, S. & Kaye, S.
(2017). Olaparib and somatic BRCA mutations. Oncotarget,
Dougherty, B.A., Lai, Z., Hodgson, D.R., Orr, M.C., Hawryluk, M., Sun, J., Yelensky, R., Spencer, S.K., Robertson, J.D., Ho, T.W., et al.
(2017). Biological and clinical evidence for somatic mutations in BRCA1 and BRCA2 as predictive markers for olaparib response in high-grade serous ovarian cancers in the maintenance setting. Oncotarget,
Dolly, S.O., Migali, C., Tunariu, N., Della-Pepa, C., Khakoo, S., Hazell, S., de Bono, J.S., Kaye, S.B. & Banerjee, S.
(2017). Indolent peritoneal mesothelioma: PI3K-mTOR inhibitors as a novel therapeutic strategy. Esmo open,
George, A., Kaye, S. & Banerjee, S.
(2017). Delivering widespread BRCA testing and PARP inhibition to patients with ovarian cancer. Nature reviews clinical oncology,
George, A., Kristeleit, R., Rafii, S., Michie, C.O., Bowen, R., Michalarea, V., van Hagen, T., Wong, M., Rallis, G., Molife, L.R., et al.
(2017). Clinical factors of response in patients with advanced ovarian cancer participating in early phase clinical trials. European journal of cancer,
Capoluongo, E., Ellison, G., López-Guerrero, J.A., Penault-Llorca, F., Ligtenberg, M.J., Banerjee, S., Singer, C., Friedman, E., Markiefka, B., Schirmacher, P., et al.
(2017). Guidance Statement On BRCA1/2 Tumor Testing in Ovarian Cancer Patients. Seminars in oncology,
Pujade-Lauraine, E., Ledermann, J.A., Selle, F., Gebski, V., Penson, R.T., Oza, A.M., Korach, J., Huzarski, T., Poveda, A., Pignata, S., et al.
(2017). Olaparib tablets as maintenance therapy in patients with platinum-sensitive, relapsed ovarian cancer and a BRCA1/2 mutation (SOLO2/ENGOT-Ov21): a double-blind, randomised, placebo-controlled, phase 3 trial. The lancet oncology,
(2017). Bevacizumab in cervical cancer: a step forward for survival. The lancet,
George, A., McLachlan, J., Tunariu, N., Della Pepa, C., Migali, C., Gore, M., Kaye, S. & Banerjee, S.
(2017). The role of hormonal therapy in patients with relapsed high-grade ovarian carcinoma: a retrospective series of tamoxifen and letrozole. Bmc cancer,
Orbegoso, C., Marquina, G., George, A. & Banerjee, S.
(2017). The role of Cediranib in ovarian cancer. Expert opinion on pharmacotherapy,
Rafii, S., Gourley, C., Kumar, R., Geuna, E., Ang, J.E., Rye, T., Chen, L.-., Shapira-Frommer, R., Friedlander, M., Matulonis, U., et al.
(2017). Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer. Oncotarget,
Phelan, C.M., Kuchenbaecker, K.B., Tyrer, J.P., Kar, S.P., Lawrenson, K., Winham, S.J., Dennis, J., Pirie, A., Riggan, M.J., Chornokur, G., et al.
(2017). Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer. Nat genet,
To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC..
Heath, O.M., van Beekhuizen, H.J., Nama, V., Kolomainen, D., Nobbenhuis, M.A., Ind, T.E., Sohaib, S.A., Lofts, F.J., Heenan, S., Gore, M., et al.
(2016). Venous thromboembolism at time of diagnosis of ovarian cancer: Survival differs in symptomatic and asymptomatic cases. Thrombosis research,
McLachlan, J., Lima, J.P., Dumas, L. & Banerjee, S.
(2016). Targeted agents and combinations in ovarian cancer: where are we now?. Expert review of anticancer therapy,
McLachlan, J. & Banerjee, S.
(2016). Olaparib for the treatment of epithelial ovarian cancer. Expert opinion on pharmacotherapy,
Moschetta, M., George, A., Kaye, S.B. & Banerjee, S.
(2016). BRCA somatic mutations and epigenetic BRCA modifications in serous ovarian cancer. Annals of oncology,
McLachlan, J., Gore, M. & Banerjee, S.
(2016). Targeting the mitogen-activated protein kinase pathway in low-grade serous carcinoma of the ovary. Pharmacogenomics,
McLachlan, J., George, A. & Banerjee, S.
(2016). The Current Status of PARP Inhibitors in Ovarian Cancer. Tumori journal,
Dittrich, C., Kosty, M., Jezdic, S., Pyle, D., Berardi, R., Bergh, J., El-Saghir, N., Lotz, J.-., Österlund, P., Pavlidis, N., et al.
(2016). ESMO / ASCO Recommendations for a Global Curriculum in Medical Oncology Edition 2016. Esmo open,
Dumas, L., Ring, A., Butler, J., Kalsi, T., Harari, D. & Banerjee, S.
(2016). Improving outcomes for older women with gynaecological malignancies. Cancer treatment reviews,
Vergote, I., Banerjee, S., Gerdes, A.-., van Asperen, C., Marth, C., Vaz, F., Ray-Coquard, I., Stoppa-Lyonnet, D., Gonzalez-Martin, A., Sehouli, J., et al.
(2016). Current perspectives on recommendations for BRCA genetic testing in ovarian cancer patients. European journal of cancer,
Friedlander, M., Banerjee, S., Mileshkin, L., Scott, C., Shannon, C. & Goh, J.
(2016). Practical guidance on the use of olaparib capsules as maintenance therapy for women withBRCAmutations and platinum-sensitive recurrent ovarian cancer. Asia-pacific journal of clinical oncology,
Morgan, G., Lambertini, M., Kourie, H.R., Amaral, T., Argiles, G., Banerjee, S., Cardone, C., Corral, J., De Mattos-Arruda, L., Öztürk, A., et al.
(2016). Career opportunities and benefits for young oncologists in the European Society for Medical Oncology (ESMO). Esmo open,
Percival, N., George, A., Gyertson, J., Hamill, M., Fernandes, A., Davies, E., Rahman, N. & Banerjee, S.
(2016). The integration of BRCA testing into oncology clinics. British journal of nursing,
Meeks, H.D., Song, H., Michailidou, K., Bolla, M.K., Dennis, J., Wang, Q., Barrowdale, D., Frost, D., Embrace, , McGuffog, L., et al.
(2016). BRCA2 Polymorphic Stop Codon K3326X and the Risk of Breast, Prostate, and Ovarian Cancers. J natl cancer inst,
BACKGROUND: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic mutations might account for this association. There is scant information about the effect of K3326X in other hormone-related cancers. METHODS: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided. RESULTS: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10(-) (6)) and invasive ovarian cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10(-3)). These associations were stronger for serous ovarian cancer and for estrogen receptor-negative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10(-5) and ORw = 1.50, 95% CI = 1.28 to 1.76, P = 4.1x10(-5), respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No association with prostate cancer was observed. CONCLUSIONS: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological mechanism of action responsible for these associations..
McLachlan, J. & Banerjee, S.
(2015). Pazopanib in ovarian cancer. Expert review of anticancer therapy,
Younger, E., Okines, A.F., Tan, D.S., Anandappa, G., Tokaca, N., Thomas, B., Gore, M., Kaye, S. & Banerjee, S.
(2015). CARBOPLATIN DESENSITISATION EXPERIENCE IN CLINICAL PRACTICE. International journal of gynecological cancer,
Lima, J., Mclachlan, J., della Peppa, C., Nobbenhuis, M., Gore, M., Kaye, S. & Banerjee, S.
(2015). CLINICAL OUTCOMES OF LOW GRADE SEROUS OVARIAN CARCINOMA: A TWENTY FIVE YEAR RETROSPECTIVE CASE SERIES OF THE ROYAL MARSDEN EXPERIENCE. International journal of gynecological cancer,
Kolomainen, D.F., Butler, J., Barton, D.P., Ind, T.E., Nobbenhuis, M.A., Lalondrelle, S., Taylor, A., Shepherd, J.H., Gore, M.E., Kaye, S.B., et al.
(2015). IS THERE A SURVIVAL BENEFIT FOR PATIENTS WHO RECEIVE POST-OPERATIVE ADJUVANT CHEMOTHERAPY FOLLOWING SECONDARY CYTOREDUCTIVE SURGERY (SCRS) FOR RECURRENT EPITHELIAL OVARIAN CANCER (EOC)?. International journal of gynecological cancer,
Heath, O., van Beekhuizen, H., Kolomainen, D., Nama, V., Nobbenhuis, M., Ind, T., Sohaib, A., Lofts, F., Heenan, S., Gore, M., et al.
(2015). SYMPTOMATIC AND ASYMPTOMATIC VENOUS THROMBOEMBOLISM AT TIME OF DIAGNOSIS OF PRIMARY OVARIAN CANCER. International journal of gynecological cancer,
Seifert, H., Georgiou, A., Alexander, H., McLachlan, J., Bodla, S., Kaye, S., Barton, D., Nobbenhuis, M., Gore, M. & Banerjee, S., et al.
(2015). Poor performance status (PS) is an indication for an aggressive approach to neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer (EOC). Gynecologic oncology,
Symonds, R.P., Gourley, C., Davidson, S., Carty, K., McCartney, E., Rai, D., Banerjee, S., Jackson, D., Lord, R., McCormack, M., et al.
(2015). Cediranib combined with carboplatin and paclitaxel in patients with metastatic or recurrent cervical cancer (CIRCCa): a randomised, double-blind, placebo-controlled phase 2 trial. The lancet oncology,
Seifert, H., Georgiou, A., Alexander, H., McLachlan, J., Bodla, S., Kaye, S., Barton, D., Nobbenhuis, M., Gore, M. & Banerjee, S., et al.
(2015). Poor performance status (PS) is an indication for an aggressive approach to neoadjuvant chemotherapy in patients with advanced epithelial ovarian cancer (EOC). Gynecologic oncology,
Lan, C., Heindl, A., Huang, X., Xi, S., Banerjee, S., Liu, J. & Yuan, Y.
(2015). Quantitative histology analysis of the ovarian tumour microenvironment. Scientific reports,
Boussios, S., Attygalle, A., Hazell, S., Moschetta, M., Mclachlan, J., Okines, A. & Banerjee, S.
(2015). Malignant Ovarian Germ Cell Tumors in Postmenopausal Patients: The Royal Marsden Experience and Literature Review. Anticancer research,
Banerjee, S. & Stanway, S.
(2015). Problem solving in acute oncology. British journal of cancer,
Boussios, S., Moschetta, M., McLachlan, J. & Banerjee, S.
(2015). Bleomycin-Induced Flagellate Erythema in a Patient Diagnosed with Ovarian Yolk Sac Tumor. Case reports in oncological medicine,
Flagellate linear hyperpigmentation can rarely be caused by the chemotherapy agent, bleomycin. Herein, we describe the case of a 20-year-old woman treated with bleomycin for an ovarian yolk sac tumor and review the prominent features of this form of dermatitis..
Syrios, J., Banerjee, S. & Kaye, S.B.
(2014). Advanced Epithelial Ovarian Cancer: From Standard Chemotherapy to Promising Molecular Pathway Targets - Where Are we Now?. Anticancer research,
Califano, R., Karamouzis, M.V., Banerjee, S., de Azambuja, E., Guarneri, V., Hutka, M., Jordan, K., Kamposioras, K., Martinelli, E., Corral, J., et al.
(2014). Use of adjuvant chemotherapy (CT) and radiotherapy (RT) in incompletely resected (R1) early stage Non-Small Cell Lung Cancer (NSCLC): a European survey conducted by the European Society for Medical Oncology (ESMO) young oncologists committee. Lung cancer,
BACKGROUND: Early stage Non-Small Cell Lung Cancer (NSCLC) is potentially curable with surgery. ESMO guidelines recommend cisplatin-based adjuvant chemotherapy (CT) for completely resected stage II-III NSCLC. There is limited evidence for the use of adjuvant CT and/or radiotherapy (RT) in incompletely resected (R1) early stage NSCLC. MATERIALS AND METHODS: A European survey of thoracic oncologists was conducted to evaluate use of adjuvant CT and RT for R1-resected NSCLC and to identify factors influencing treatment decisions. Demographics and information on clinical stage, regimens, cycles planned, radiotherapy sites, multidisciplinary management and discussion about inconclusive evidence with the patient were collected. Univariate and multivariate analyses were performed. RESULTS: 768 surveys were collected from 41 European countries. 82.9% of participants were medical oncologists; 49.3% ESMO members; 37.1% based in University Hospitals; 32.6% practicing oncology for over 15 years and 81.4% active in research. 91.4% of participants prescribed adjuvant CT and mostly cisplatin/vinorelbine (81.2%) or cisplatin/gemcitabine (42.9%). 85% discussed limited clinical evidence with the patient. In the univariate analysis, a statistically significant association with CT prescription was found for medical oncology specialty (p<0.001), ESMO membership (p<0.001), activity in clinical research (p=0.002) and increased frequency of ESMO guidelines consultation (p for trend <0.001). 48.3% of participants prescribed adjuvant RT and its prescription were associated with radiation oncology specialty (p<0.001), not being an ESMO member (p<0.001), years practicing specialty (p for trend=0.001), workload of lung cancer patients (p for trend=0.027) and decreased frequency in consulting ESMO guidelines (p<0.001). In the multivariate analysis, medical oncology and radiation oncology were the best discriminator for prescription of adjuvant CT and RT, respectively. CONCLUSION: This survey demonstrates that adjuvant CT and RT are commonly used in clinical practice for R1-resected NSCLC despite limited evidence. Prospective trials are necessary to clarify optimal management in this setting..
Nobbenhuis, M.A., Lalondrelle, S., Larkin, J. & Banerjee, S.
(2014). Management of melanomas of the gynaecological tract. Curr opin oncol,
PURPOSE OF REVIEW: Primary melanomas originating from the gynaecological tract are rare and aggressive cancers. The 5-year survival is around 10%. The majority of tumours differ from cutaneous melanomas, which arise from the skin, by developing from melanocytes located in mucosal epithelium. The clinical behaviour, prognosis and the biology of mucosal melanomas are distinct from cutaneous melanomas. In this article, we summarize the current management of melanomas of the gynaecological tract (vulva, vagina, ovary and cervix) and discuss the progress in developing new treatments. RECENT FINDINGS: The management of mucosal melanomas has not changed substantially over the last decade and the prognosis remains poor. Surgery remains the primary treatment of choice in all localized melanomas of the genital tract. Radiotherapy and chemotherapy are options but have limited success for the majority of women. Activation of c-KIT occurs in vulvar melanomas. Clinical trials of targeted agents are underway. SUMMARY: As a result of the rarity of gynaecological tract melanomas, challenges associated with their anatomical locations and resistance to conventional radiotherapy and chemotherapy, this group of conditions remain difficult to treat and continue to have a poor prognosis. A greater understanding of the molecular profile of these cancers may provide promising targeted approaches..
Penson, R.T., Moore, K.M., Fleming, G.F., Braly, P., Schimp, V., Nguyen, H., Matulonis, U.A., Banerjee, S., Haluska, P., Gore, M., et al.
(2014). A phase II study of ramucirumab (IMC-1121B) in the treatment of persistent or recurrent epithelial ovarian, fallopian tube or primary peritoneal carcinoma. Gynecol oncol,
OBJECTIVE: Vascular endothelial growth factor (VEGF) receptor-mediated signaling contributes to ovarian cancer pathogenesis. Elevated VEGF expression is associated with poor clinical outcomes. We investigated ramucirumab, a fully human anti-VEGFR-2 antibody, in patients with persistent or recurrent epithelial ovarian, fallopian tube, or primary peritoneal carcinoma. Primary endpoints were progression-free survival at 6 months (PFS-6) and confirmed objective response rate (ORR). METHODS: Women who received ≥ 1 platinum-based chemotherapeutic regimen and had a platinum-free interval of <12 months with measurable disease were eligible. Patients received 8 mg/kg ramucirumab intravenously every 2 weeks. RESULTS: Sixty patients were treated; one patient remained on study as of September 2013. The median age was 62 years (range: 27-80), and median number of prior regimens was 3. Forty-five (75%) patients had platinum refractory/resistant disease. Thirty-nine patients (65.0%) had serous tumors. PFS-6 was 25.0% (n=15/60, 95% CI: 14.7-37.9%). Best overall response was: partial response 5.0% (n=3/60), stable disease 56.7% (n=34/60), and progressive disease 33.3% (n=20/60). The most common treatment-emergent adverse events possibly related to study drug were headache (65.0%; 10.0% Grade ≥ 3), fatigue (56.7%; 3.3% Grade ≥ 3), diarrhea (28.3%; 1.7% Grade ≥ 3), hypertension (25.0%; 3.3% Grade ≥ 3), and nausea (20.0%; no Grade ≥ 3). Two patients experienced intestinal perforations (3.3% Grade ≥ 3). Pharmacodynamic analyses revealed changes in several circulating VEGF proteins following initial ramucirumab infusion, including increased VEGF-A, PlGF and decreased sVEGFR-2. CONCLUSIONS: Although antitumor activity was observed, the predetermined efficacy endpoints were not met..
George, A., Smith, F., Cloke, V., Gore, M.E., Hanson, H., Banerjee, S. & Rahman, N.
(2014). 881PDIMPLEMENTATION OF ROUTINE BRCA GENE TESTING OF OVARIAN CANCER (OC) PATIENTS AT ROYAL MARSDEN HOSPITAL. Annals of oncology,
Canario, R., Lima, J.P., Migali, C., Tunariu, N., George, A., Kaye, S.B., Gore, M.E. & Banerjee, S.
(2014). 877PDCLINICAL OUTCOMES OF RECURRENT OVARIAN GRANULOSA CELL TUMOURS TREATED WITH LETROZOLE: A 10-YEAR RETROSPECTIVE CASE-SERIES OF THE ROYAL MARSDEN HOSPITAL. Annals of oncology,
McNeish, I.A., Ledermann, J.A., Webber, L., James, L., Kaye, S.B., Hall, M., Hall, G., Clamp, A., Earl, H., Banerjee, S., et al.
(2014). A randomised, placebo-controlled trial of weekly paclitaxel and saracatinib (AZD0530) in platinum-resistant ovarian, fallopian tube or primary peritoneal cancer†. Ann oncol,
BACKGROUND: We investigated whether the Src inhibitor saracatinib (AZD0530) improved efficacy of weekly paclitaxel in platinum-resistant ovarian cancer. PATIENTS AND METHODS: Patients with platinum-resistant ovarian, fallopian tube or primary peritoneal cancer were randomised 2 : 1 to receive 8-week cycles of weekly paclitaxel (wPxl; 80 mg/m(2)/week ×6 with 2-week break) plus saracatinib (S; 175 mg o.d.) or placebo (P) continuously, starting 1 week before wPxl, until disease progression. Patients were stratified by taxane-free interval (<6 versus ≥6 months/no prior taxane). The primary end point was progression-free survival (PFS) rate at 6 months. Secondary end points included overall survival (OS) and response rate (RR). RESULTS: A total of 107 patients, median age 63 years, were randomised. Forty-three (40%) had received >2 lines of prior chemotherapy. The 6-month PFS rate was 29% (wPxl + S) versus 34% (wPxl + P) (P = 0.582). Median PFS was 4.7 versus 5.3 months (hazard ratio 1.00, 95% confidence interval 0.65-1.54; P = 0.99). RR (complete + partial) was 29% (wPxl + S) versus 43% (wPxl + P), P value = 0.158. Grade 3/4 adverse events were 36% versus 31% (P = 0.624); the most frequent G3/4 toxicities were vomiting (5.8% saracatinib versus 8.6% placebo), abdominal pain (5.8% versus 0%) and diarrhoea (4.3% versus 5.7%). Febrile neutropenia was more common in the saracatinib arm (4.3%) than placebo (0%). Response, PFS and OS were all significantly (P < 0.05) better in patients with taxane interval ≥6 months/no prior taxane (n = 85) than those <6 months (n = 22), regardless of randomisation. CONCLUSIONS: Saracatinib does not improve activity of weekly paclitaxel in platinum-resistant ovarian cancer. Taxane-free interval of ≥6 months/no prior taxane was associated with better outcome in both groups. TRIALS REGISTRATION: Clinicaltrials.gov NCT01196741; ISRCTN 32163062..
Thway, K., Hazell, S., Banerjee, S. & Fisher, C.
(2014). Rhabdomyosarcoma with pseudolipoblasts arising in ovarian carcinosarcoma: a distinctive postchemotherapy morphologic variant mimicking pleomorphic liposarcoma. Case rep pathol,
We describe a case of ovarian carcinosarcoma occurring in a 60-year-old female. The neoplasm was excised after neoadjuvant chemotherapy and contained a predominant heterologous pleomorphic rhabdomyosarcomatous component in which there were numerous multivacuolated rhabdomyoblasts that strongly mimicked lipoblasts. The clear cell variant of rhabdomyosarcoma is rarely documented, but this case shows a highly unusual finding in which the rhabdomyoblasts show the prominent multivacuolation with nuclear indentation characteristic of and indistinguishable from pleomorphic lipoblasts. This appears to represent a posttreatment phenomenon. As this finding might conceivably occur in other rhabdomyosarcomas after chemotherapy, we highlight the potential for diagnostic confusion with pleomorphic liposarcoma, which is usually diagnosed by morphology so that immunohistochemistry for muscle markers might not be performed. .
Della Pepa, C. & Banerjee, S.
(2014). Bevacizumab in combination with chemotherapy in platinum-sensitive ovarian cancer. Onco targets ther,
Targeting angiogenesis is proving to be a successful approach in the management of ovarian cancer. The vascular endothelial growth factor inhibitor, bevacizumab, is the first angiogenesis inhibitor to have shown a significant progression-free survival advantage in the Phase III setting. There is now evidence supporting the use of bevacizumab in combination with chemotherapy for first-line and relapsed (platinum-sensitive and resistant) ovarian cancer. In this review, we summarize the positive Phase III trial (OCEANS [Ovarian Cancer Study Comparing Efficacy and Safety of Chemotherapy and Anti-Angiogenic Therapy in Platinum-Sensitive Recurrent Disease]) that led to European Medicines Agency approval of bevacizumab in platinum-sensitive first relapse and discuss the best use of the drug in this disease. .
Banerjee, S. & Kaye, S.B.
(2013). New strategies in the treatment of ovarian cancer: current clinical perspectives and future potential. Clin cancer res,
The treatment of ovarian cancer is set to undergo rapid changes, as strategies incorporating molecular targeted therapies begin to take shape. These are based on a better appreciation of approaches targeting the tumor microenvironment as well as specific subtypes of the disease, with distinct molecular aberrations. Targeting the VEGF pathway through bevacizumab is clearly effective, with positive randomized trials at all disease stages; targeting defective homologous recombination repair pathways with PARP inhibitors is also proving successful in a substantial proportion of patients with high-grade serous ovarian cancer. In this article, we will review progress in these two leading areas and also discuss the potential for targeting other pathways and receptors that may be activated in ovarian cancer, including the RAS/RAF/MEK and PI3K/AKT/mToR pathways, the ErbB and IGF family of receptors, mitotic check points, and also the folate receptor. Here, single-agent therapy may play a role in selected cases but essential components of future strategies should include combination treatments aimed at dealing with the key problem of drug resistance, together with rational approaches to patient selection..
Weigel, M.T., Banerjee, S., Arnedos, M., Salter, J., A'Hern, R., Dowsett, M. & Martin, L.A.
(2013). Enhanced expression of the PDGFR/Abl signaling pathway in aromatase inhibitor-resistant breast cancer. Ann oncol,
BACKGROUND: We have found that the platelet-derived growth factor receptor (PDGFR)/Abl signaling pathway is up-regulated as a determinant of the acquisition of resistance to estrogen deprivation in vitro. We aimed to determine its clinical relevance in aromatase inhibitor (AI)-resistant breast cancer. PATIENTS AND METHODS: We identified a cohort of 45 patients with estrogen receptor-positive breast cancer who had been treated with an AI, subsequently relapsed and had biopsy material available from both the presentation and post-AI recurrent lesion. PDGFRα, PDGFRβ and Abl expression was assessed in formalin-fixed paraffin-embedded sections. RESULTS: Tumor protein expression of PDGFRα (1.39-fold, P=0.0065), PDGFRβ (4.32-fold, P=0.006) and Abl (1.8-fold, P=0.001) was increased at the point of relapse. Tumor and stromal expression of PDGFRα as well as PDGFRβ was significantly correlated in pre-treatment and relapse samples. High post-treatment tumor and stromal PDGFRβ levels were associated with a short time to treatment failure (TTF). Expression of PDGFRα in relapsing tumor specimens was correlated with Abl expression and Ki67 levels. Furthermore, changes in Abl correlated significantly with changes in ER expression. CONCLUSIONS: These clinical data support a role for enhanced PDGF/Abl signaling in AI-resistant disease and provide a rationale for targeting the pathway in endocrine-resistant breast cancer..
Ang, J.E., Gourley, C., Powell, C.B., High, H., Shapira-Frommer, R., Castonguay, V., De Greve, J., Atkinson, T., Yap, T.A., Sandhu, S., et al.
(2013). Efficacy of chemotherapy in BRCA1/2 mutation carrier ovarian cancer in the setting of PARP inhibitor resistance: a multi-institutional study. Clin cancer res,
PURPOSE: Preclinical data suggest that exposure to PARP inhibitors (PARPi) may compromise benefit to subsequent chemotherapy, particularly platinum-based regimens, in patients with BRCA1/2 mutation carrier ovarian cancer (PBMCOC), possibly through the acquisition of secondary BRCA1/2 mutations. The efficacy of chemotherapy in the PARPi-resistant setting was therefore investigated. EXPERIMENTAL DESIGN: We conducted a retrospective review of PBMCOC who received chemotherapy following disease progression on olaparib, administered at ≥200 mg twice daily for one month or more. Tumor samples were obtained in the post-olaparib setting where feasible and analyzed by massively parallel sequencing. RESULTS: Data were collected from 89 patients who received a median of 3 (range 1-11) lines of pre-olaparib chemotherapy. The overall objective response rate (ORR) to post-olaparib chemotherapy was 36% (24 of 67 patients) by Response Evaluation Criteria in Solid Tumors (RECIST) and 45% (35 of 78) by RECIST and/or Gynecologic Cancer InterGroup (GCIG) CA125 criteria with median progression-free survival (PFS) and overall survival (OS) of 17 weeks [95% confidence interval (CI), 13-21] and 34 weeks (95% CI, 26-42), respectively. For patients receiving platinum-based chemotherapy, ORRs were 40% (19 of 48) and 49% (26/53), respectively, with a median PFS of 22 weeks (95% CI, 15-29) and OS of 45 weeks (95% CI, 15-75). An increased platinum-to-platinum interval was associated with an increased OS and likelihood of response following post-olaparib platinum. No evidence of secondary BRCA1/2 mutation was detected in tumor samples of six PARPi-resistant patients [estimated frequency of such mutations adjusted for sample size: 0.125 (95%-CI: 0-0.375)]. CONCLUSIONS: Heavily pretreated PBMCOC who are PARPi-resistant retain the potential to respond to subsequent chemotherapy, including platinum-based agents. These data support the further development of PARPi in PBMCOC..
Banerjee, S., Rustin, G., Paul, J., Williams, C., Pledge, S., Gabra, H., Skailes, G., Lamont, A., Hindley, A., Goss, G., et al.
(2013). A multicenter, randomized trial of flat dosing versus intrapatient dose escalation of single-agent carboplatin as first-line chemotherapy for advanced ovarian cancer: an SGCTG (SCOTROC 4) and ANZGOG study on behalf of GCIG. Ann oncol,
BACKGROUND: The aim of the study is to demonstrate that intrapatient dose escalation of carboplatin would improve the outcome in ovarian cancer compared with flat dosing. PATIENTS AND METHODS: Patients with untreated stage IC-IV ovarian cancer received six cycles of carboplatin area under the curve 6 (AUC 6) 3 weekly either with no dose modification except for toxicity (Arm A) or with dose escalations in cycles 2-6 based on nadir neutrophil and platelet counts (Arm B). The primary end-point was progression-free survival (PFS). RESULTS: Nine hundred and sixty-four patients were recruited from 71 centers. Dose escalation was achieved in 77% of patients who had ≥1 cycle. The median AUCs (cycle 2-6) received were 6.0 (Arm A) and 7.2 (Arm B) (P < 0.001). Grade 3/4 non-hematological toxicity was higher in Arm B (31% versus 22% P = 0.001). The median PFS was 12.1 months in Arm A and B [hazard ratio (HR) 0.99; 95% confidence interval (CI) 0.85-1.15; P = 0.93]. The median overall survival (OS) was 34.1 and 30.7 months in Arms A and B, respectively (HR 0.98; 95% CI 0.81-1.18, P = 0.82). In multivariate analysis, baseline neutrophil (P < 0.001), baseline platelet counts (P < 0.001) and the difference between white blood cell (WBC) and neutrophil count (P = 0.009) had a significant adverse prognostic value. CONCLUSIONS: Intrapatient dose escalation of carboplatin based on nadir blood counts is feasible and safe. However, it provided no improvement in PFS or OS compared with flat dosing. Baseline neutrophils over-ride nadir counts in prognostic significance. These data may have wider implications particularly in respect of the management of chemotherapy-induced neutropenia..
Tan, D.S., Yap, T.A., Hutka, M., Roxburgh, P., Ang, J., Banerjee, S., Grzybowska, E., Gourley, C., Gore, M.E. & Kaye, S.B., et al.
(2013). Implications of BRCA1 and BRCA2 mutations for the efficacy of paclitaxel monotherapy in advanced ovarian cancer. Eur j cancer,
INTRODUCTION: Preclinical data suggest that BRCA1 and BRCA2 (BRCA1/2)-mutated ovarian cancers (BMOC) are exquisitely sensitive to platinum-salts, but resistant to microtubule-stabilizing anticancer agents. The clinical relevance of these preclinical data is unclear, since there are currently no published data on the efficacy of single-agent taxane chemotherapy in patients with BMOC. A retrospective study was undertaken to investigate the clinical effects of paclitaxel monotherapy in patients with BMOC. METHODS: Clinical data on responses and progression-free-survival (PFS) following paclitaxel (3-weekly/weekly) monotherapy in BMOC patients were collected from four cancer centres. Antitumour response was defined as RECIST partial or complete response (PR/CR), and clinical benefit was defined as PR/CR and stable disease (SD) lasting at least 18 weeks. Comparisons of the rate and duration of response and clinical benefit between categorical variables (e.g. platinum-sensitive versus platinum-resistant patients) were undertaken. RESULTS: We identified 26 BMOC patients who received paclitaxel monotherapy for relapsed disease, of which 15/26 (58%) were platinum-sensitive and 11/26 (42%) were platinum-resistant. The response rate to paclitaxel monotherapy was 46% (12/26). Clinical benefit rate was significantly higher in platinum-sensitive than platinum-resistant patients (80% versus 36%, p=0.04). BMOC patients with platinum-sensitive disease had significantly longer median PFS compared with platinum-resistant patients (42 versus 21 weeks, p=0.003). CONCLUSIONS: These data provide the first clinical evidence that paclitaxel monotherapy is active in BMOC and may be more effective in platinum-sensitive BMOC..
Banerjee, S. & Gore, M.
(2013). Personalized therapy in gynecological cancer: a reality in clinical practice?. Curr oncol rep,
Miller, R.E. & Banerjee, S.
(2013). The current state of pemetrexed in ovarian cancer. Expert opin investig drugs,
INTRODUCTION: Pemetrexed is a multitargeted antifolate drug that has shown benefit in several clinical trials in solid tumors. It is currently approved for the treatment of nonsmall cell lung cancer (NSCLC) and mesothelioma, and is being explored in epithelial ovarian cancer. AREAS COVERED: In this article, the clinical development of pemetrexed in relation to ovarian cancer is discussed. Early phase clinical trials using pemetrexed monotherapy or in combination with other cytotoxic or target agents are reviewed. The safety profile of pemetrexed will also be evaluated. EXPERT OPINION: A number of Phase I and II clinical trials have evaluated the use of pemetrexed in patients with ovarian cancer. Thus far, there are no randomized studies that address the role of pemetrexed compared to current, standard treatments. The activity of single agent pemetrexed in platinum-resistant patients is worth exploring. Biomarker-driven randomized, clinical trials and patient selection are key for the future development of pemetrexed..
Jenkins, V., Catt, S., Banerjee, S., Gourley, C., Montes, A., Solis-Trapala, I., Monson, K. & Fallowfield, L.
(2013). Patients' and oncologists' views on the treatment and care of advanced ovarian cancer in the UK: results from the ADVOCATE study. British journal of cancer,
Lopez, J., Banerjee, S. & Kaye, S.B.
(2013). New developments in the treatment of ovarian cancer--future perspectives. Ann oncol,
Vol.24 Suppl 10,
Over the past 40 years, the treatment of ovarian cancer has undoubtedly improved as a result of better multi-modality care and platinum-based chemotherapy. More recently, the introduction of anti-angiogenic therapy, PARP inhibitors and a weekly regimen for paclitaxel indicate that results are likely to improve further. However, major challenges remain and these will be reviewed in this article. We assess key issues in anti-angiogenic treatment including potential ways for addressing resistance; we review the current studies of PARP inhibitor treatment, which shows most promise in patients with germline BRCA mutations; we describe the potential for folate-receptor-directed therapy, given the high level of FR expression in ovarian cancer and we highlight the potential for molecular targeted therapy, focusing on specific subgroups of the disease with targets such as the PI3 K/AKT and RAS/RAF/MEK pathways and the ErbB family of oncogenes. We anticipate that progress will accelerate with a better understanding of the molecular pathogenesis of the various subtypes of ovarian cancer, leading to an increasingly personalized approach to treating women with this disease. .
Weigelt, B. & Banerjee, S.
(2012). Molecular targets and targeted therapeutics in endometrial cancer. Current opinion in oncology,
Banerjee, S. & Kaye, S.
(2012). Progression-free survival versus overall survival in ovarian cancer: where are we now?. Curr oncol rep,
Banerjee, S. & Gore, M.
(2012). Recent advances in systemic treatments for ovarian cancer. Cancer imaging,
Ovarian cancer remains the leading cause of death from gynaecological cancer. Advances in surgical and chemotherapeutic strategies have led to improvements in outcome. However, the majority of women present with advanced disease with little prospect for cure. In this article, we summarize the systemic management and ovarian cancer and raise a number of important issues: namely the timing of systemic therapy in relation to surgery, the selection of patients who do not require systemic therapy and the development of novel agents..
Banerjee, S. & Kaye, S.B.
(2012). Gynecological cancer: First-line bevacizumab for ovarian cancer--new standard of care?. Nat rev clin oncol,
(2011). The combination of VEGF inhibitors and anti-oestrogen therapies in breast cancer. Steroids,
Despite effective treatments for oestrogen receptor-positive breast cancers, drug resistance is common and remains a significant clinical challenge. Targeting tumour vasculature by blockade of the vascular endothelial growth factor (VEGF) has proved successful in a variety of cancers. Phase III clinical trials of bevacizumab in combination with chemotherapy showed some efficacy in breast cancer. Concomitant targeting of the VEGF and oestrogen signalling pathways has the potential to provide enhanced therapeutic benefit in oestrogen receptor-positive breast cancer, and this strategy is under evaluation in clinical trials. This article summarises the rationale for this approach and clinical studies so far..
Banerjee, S. & Kaye, S.
(2011). The role of targeted therapy in ovarian cancer. Eur j cancer,
Vol.47 Suppl 3,
Ovarian cancer is the second most common gynaecological malignancy and the leading cause of death from gynaecological cancer. Although in some cases treatment is initially effective, there is a considerable risk of disease recurrence and resistance to therapy. Therapies targeting molecular alterations in tumours offer the promise of significantly improved treatment. So far, the most promising targeted agents are angiogenesis inhibitors and PARP inhibitors. Here, we review the various targeted therapeutic approaches under clinical investigation in phase I and II trials of ovarian cancer and the challenges facing their future success in the clinic..
Banerjee, S. & Kaye, S.
(2011). PARP inhibitors in BRCA gene-mutated ovarian cancer and beyond. Curr oncol rep,
Poly(ADP-ribose)polymerase (PARP) inhibitors are showing considerable promise for the treatment of BRCA mutation-associated ovarian and breast cancer. This approach exploits a synthetic lethal strategy to target the specific DNA repair pathway in cancers that harbor mutations in the BRCA1 or BRCA2 genes. Accumulating evidence suggests that PARP inhibitors may have a wider application in the treatment of sporadic, high-grade serous ovarian cancers and other cancers including endometrial cancer. In this review, we discuss the clinical development of PARP inhibitors in ovarian cancer and explore challenges that need to be addressed if the full potential of these agents is to be realized..
Sanfilippo, R., Grosso, F., Jones, R.L., Banerjee, S., Pilotti, S., D'Incalci, M., Tos, A.P., Raspagliesi, F., Judson, I. & Casali, P.G., et al.
(2011). Trabectedin in advanced uterine leiomyosarcomas: A retrospective case series analysis from two reference centers. Gynecologic oncology,
Weigel, M.T., Banerjee, S., A'Hern, R., Arnedos, M., Ghazoui, Z., Dunbier, A.K., Dowsett, M. & Martin, L.-.
(2011). P4-01-01: Preclinical and Clinical Studies of Estrogen Deprivation Support the PDGF/Abl Pathway as a Novel Therapeutic Target for Overcoming Resistance. Poster session abstracts,
Banerjee, S.N., Mitchell, S., Al-Muderis, O., Pennert, K., Dunlop, A., Propert-Lewis, C., Judson, I.R. & Scurr, M.R.
(2011). The Royal Marsden Hospital experience of trabectedin in patients with advanced soft tissue sarcoma (STS): Toxicity and efficacy in a nonselected group. Journal of clinical oncology,
Harb, W.A., Sessa, C., Hirte, H.W., Kaye, S.B., Simantov, R., Banerjee, S.N., Christinat, A., Sternberg, D.W., Singh, M., Light, R., et al.
(2011). A phase I study evaluating the combination of OSI-906, a dual inhibitor of insulin growth factor-1 receptor (IGF-1R) and insulin receptor (IR) with weekly paclitaxel (PAC) in patients with advanced solid tumors. Journal of clinical oncology,
Banerjee, S.N., Mitchell, S., Al-Muderis, O., Pennert, K., Dunlop, A., Propert-Lewis, C., Judson, I.R. & Scurr, M.R.
(2011). The Royal Marsden Hospital experience of trabectedin in patients with advanced soft tissue sarcoma (STS): Toxicity and efficacy in a nonselected group. J clin oncol,
e20507 Background: Trabectedin (T) is approved in Europe for advanced soft tissue sarcoma (STS). The Royal Marsden Hospital (RMH) has treated 133 STS pts with this agent, the majority outside of clinical trial. This affords the opportunity to determine the toxicity profile and clinical benefit of T in the largest, non-selected cohort published to date. METHODS: Patients who started T as a 24 hr infusion for advanced STS between May 1999 and August 2010 were analysed for clinical outcome and toxicity. RESULTS: 133 patients were identified: 60% female; median age 50yrs (18-77yrs) and median prior treatments =1 (0-4). The histological subtypes included leiomyosarcoma (43%), myxoid liposarcoma (13%) and synovial sarcoma (12%); metastatic sites: lung (57%), liver (27%), retroperitoneal (20%). Median number of cycles was 3 (1-24); 32% ≥6 cycles, and 19% only 1 cycle (65% due to PD). Median overall PFS and OS were 67 and 153 days respectively and 28% were progression-free at 6 months. Myxoid liposarcomas were associated with significantly better PFS (median 221 vs 52 days; p=0.003), with synovial sarcomas showing a trend towards an improved PFS. Clinical benefit (PR +SD) was seen in 52% (PR=10%). Dose reductions, delays and change to q4wk schedule due to toxicity were necessary in 25%, 28% and 11% respectively. 22% required hospitalisation and 9% died within 3 weeks of therapy (3.5% toxicity-related). Overall 55% of patients experienced grade 3/4 toxicity (predominantly myelotoxicity, transaminitis, and fatigue), toxicity-related dose modification (25%), and there were 5 toxicity related deaths. Elevations in creatinine kinase occurred in 18% of cycles. CONCLUSIONS: This analysis of this largely non-selected STS cohort confirms the clinical activity of trabectedin, particularly in myxoid liposarcomas and synovial sarcomas, with approximately a third of patients experiencing prolonged disease control. Whilst it is generally well tolerated, significant toxicity was observed, with 25% of cases requiring dose reduction. Further analysis of the data is ongoing to better define those factors that may better define those not likely to benefit from T..
(2010). Becoming a new consultant: how to make it work for you. Clin med (lond),
Banerjee, S. & Cunningham, D.
(2010). Targeted therapies as adjuvant treatment for early-stage colorectal cancer: first impressions and clinical questions. Clin colorectal cancer,
Vol.9 Suppl 1,
Survival rates for metastatic colorectal cancer (CRC) have increased considerably over the years largely because of the application of optimized chemotherapy regimens. More recently, the addition of the targeted agents bevacizumab, cetuximab, and panitumumab in advanced disease has also demonstrated clinical benefit. Adjuvant chemotherapy is the standard of care in patients with early-stage CRC who are at high risk of recurrence. One challenge is how to apply targeted agents in early-stage CRC. Initial results from the NSABP-08 trial in CRC, the first report of bevacizumab in the adjuvant treatment of solid cancers, are disappointing. Nevertheless, the results of several important phase III trials of targeted adjuvant therapy are awaited. Until then, the use of targeted agents in early-stage CRC cannot be recommended. The identification of biomarkers to select patients who might derive clinical benefit is crucial in determining the full potential of targeted agents in the adjuvant setting. In this review, we discuss the biologic rationale for targeted therapies in early-stage CRC, the current clinical trials, and the clinical challenges facing the success of these agents in the adjuvant setting..
Banerjee, S., Kaye, S.B. & Ashworth, A.
(2010). Making the best of PARP inhibitors in ovarian cancer. Nat rev clin oncol,
Drugs that inhibit the enzyme poly(ADP-ribose) polymerase (PARP) are showing considerable promise for the treatment of cancers that have mutations in the BRCA1 or BRCA2 tumor suppressors. This therapeutic approach exploits a synthetic lethal strategy to target the specific DNA repair pathway in these tumors. High-grade ovarian cancers have a generally poor prognosis, and accumulating evidence suggests that mutations in BRCA1 or BRCA2, or silencing of BRCA1 by promoter methylation, may be common in this disease. Here, we consider how the potential benefit of PARP inhibitors might be maximized in ovarian cancer. We suggest that it will be crucial to explore novel therapeutic trial strategies and drug combinations, and incorporate robust biomarkers predictive of response if these drugs are to reach their full potential..
Banerjee, S. & Smith, I.E.
(2010). Management of small HER2-positive breast cancers. Lancet oncol,
Trastuzumab has revolutionised the treatment of HER2-positive early-stage breast cancer and is now standard of care in combination with chemotherapy for patients with tumours larger than 1 cm. However, 5 years after publication of the landmark trials establishing the efficacy of the drug, the management of small (≤1 cm), HER2-positive tumours remains difficult. Most small breast cancers have a good prognosis and adjuvant chemotherapy is not routinely recommended. However, retrospective data suggest that some small HER2-positive cancers might have a worse clinical outcome than others. This notion raises the key clinical question of whether patients with small HER2-positive cancers should be offered adjuvant trastuzumab and chemotherapy. The pivotal adjuvant trastuzumab trials did not include patients with tumours smaller than 1 cm, but a subset analysis of one trial showed that patients with tumours 1-2 cm in size derived at least as much clinical benefit from 1 year of adjuvant trastuzumab as did the overall cohort. Clinicians face the dilemma of whether the potential reduction in risk of recurrence in this patient group warrants the toxic effects and risks of adjuvant chemotherapy and trastuzumab. In this review, we discuss the evidence for prognosis of small HER2-positive cancers, and for possible benefit from adjuvant trastuzumab. We suggest potential treatment strategies and clinical trial designs to address this important issue. On the basis of present evidence, we recommend that the benefits and risks of adjuvant trastuzumab should be discussed with patients with small, HER2-positive breast cancer..
Banerjee, S., A'Hern, R., Detre, S., Littlewood-Evans, A.J., Evans, D.B., Dowsett, M. & Martin, L.A.
(2010). Biological Evidence for Dual Antiangiogenic-Antiaromatase Activity of the VEGFR Inhibitor PTK787/ZK222584 In vivo. Clin cancer res,
Purpose: Targeting vascular endothelial growth factor (VEGF) and estrogen receptor signaling pathways concomitantly may enhance benefit in estrogen receptor-positive breast cancer. We had shown previously that the VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 (PTK/ZK) is a competitive aromatase inhibitor in vitro. Here we investigated (a) whether PTK/ZK shows both antiangiogenic and antiaromatase inhibitory properties in vivo, and (b) whether the combination of PTK/ZK and letrozole is superior to letrozole alone.Experimental Design: Estrogen-dependent human breast cancer cells engineered to express aromatase (MCF7 AROM 1 and BT474 AROM) were used. Mice were treated with vehicle, PTK/ZK (25, 50, or 100 mg/kg), letrozole, or PTK/ZK in combination with letrozole.Results: In MCF7 AROM 1 tumors, all treatments induced growth suppression and were associated with a reduction in cell turnover index, a composite measurement of both proliferation and apoptosis. PTK/ZK significantly reduced vessel density. Whereas letrozole caused tumor regression, PTK/ZK stabilized tumor volumes. The growth suppressive and antiangiogenic effects of PTK/ZK were confirmed in BT474 AROM xenografts. The addition of PTK/ZK did not enhance the growth-suppressive effects of letrozole. However, PTK/ZK decreased progesterone receptor (PgR) and TFF1 expression and uterine weight, indicating that PTK/ZK decreases 17 beta-estradiol (E2) signaling in vivo.Conclusion: The VEGF receptor inhibitor PTK/ZK showed effects on E2-dependent gene expression consistent with aromatase inhibition as well as antiangiogenesis in xenograft models of breast cancer. The combination with letrozole was not superior to letrozole alone. Overall, these results provide further support for a potential therapeutic approach of dual inhibition of VEGF and E2 signaling using a single agent. Clin Cancer Res; 16(16); 4178-87. (C) 2010 AACR..
Banerjee, S., A'Hern, R., Detre, S., Littlewood-Evans, A.J., Evans, D.B., Dowsett, M. & Martin, L.-.
(2010). Biological evidence for dual antiangiogenic-antiaromatase activity of the VEGFR inhibitor PTK787/ZK222584 in vivo. Clin cancer res,
PURPOSE: Targeting vascular endothelial growth factor (VEGF) and estrogen receptor signaling pathways concomitantly may enhance benefit in estrogen receptor-positive breast cancer. We had shown previously that the VEGF receptor tyrosine kinase inhibitor PTK787/ZK222584 (PTK/ZK) is a competitive aromatase inhibitor in vitro. Here we investigated (a) whether PTK/ZK shows both antiangiogenic and antiaromatase inhibitory properties in vivo, and (b) whether the combination of PTK/ZK and letrozole is superior to letrozole alone. EXPERIMENTAL DESIGN: Estrogen-dependent human breast cancer cells engineered to express aromatase (MCF7 AROM 1 and BT474 AROM) were used. Mice were treated with vehicle, PTK/ZK (25, 50, or 100 mg/kg), letrozole, or PTK/ZK in combination with letrozole. RESULTS: In MCF7 AROM 1 tumors, all treatments induced growth suppression and were associated with a reduction in cell turnover index, a composite measurement of both proliferation and apoptosis. PTK/ZK significantly reduced vessel density. Whereas letrozole caused tumor regression, PTK/ZK stabilized tumor volumes. The growth suppressive and antiangiogenic effects of PTK/ZK were confirmed in BT474 AROM xenografts. The addition of PTK/ZK did not enhance the growth-suppressive effects of letrozole. However, PTK/ZK decreased progesterone receptor (PgR) and TFF1 expression and uterine weight, indicating that PTK/ZK decreases 17beta-estradiol (E2) signaling in vivo. CONCLUSION: The VEGF receptor inhibitor PTK/ZK showed effects on E2-dependent gene expression consistent with aromatase inhibition as well as antiangiogenesis in xenograft models of breast cancer. The combination with letrozole was not superior to letrozole alone. Overall, these results provide further support for a potential therapeutic approach of dual inhibition of VEGF and E2 signaling using a single agent..
Banerjee, S., Zvelebil, M., Furet, P., Mueller-Vieira, U., Evans, D.B., Dowsett, M. & Martin, L.-.
(2009). The vascular endothelial growth factor receptor inhibitor PTK787/ZK222584 inhibits aromatase. Cancer res,
Endocrine therapy is well established for the treatment of breast cancer, and antiangiogenic agents are showing considerable promise. Targeting the vascular endothelial growth factor (VEGF) and estrogen receptor (ER) signaling pathways concomitantly may provide enhanced therapeutic benefit in ER-positive breast cancer. Therefore, the effects of the VEGF receptor (VEGFR) tyrosine kinase inhibitor PTK787/ZK222584 (PTK/ZK) were investigated using human breast cancer cell lines engineered to express aromatase. As expected in this system, estrogen (E2) or androstenedione induced a proliferative response and increased ER-mediated transcription in ER-positive cell lines expressing aromatase. However, surprisingly, in the presence of androstenedione, PTK/ZK suppressed both the androstenedione-stimulated proliferation and ER-mediated transcription. PTK/ZK alone and in the presence of E2 had no observable effect on proliferation or ER-mediated transcription. These effects result from PTK/ZK having previously unrecognized antiaromatase activity and PTK/ZK being a competitive aromatase inhibitor. Computer-assisted molecular modeling showed that PTK/ZK could potentially bind directly to aromatase. The demonstration that PTK/ZK inhibits aromatase and VEGFR indicates that agents cross-inhibiting two important classes of targets in breast cancer could be developed..
Banerjee, S. & Gore, M.
(2009). The future of targeted therapies in ovarian cancer. Oncologist,
Ovarian cancer is the second most common gynecological malignancy and the leading cause of death from gynecological cancer. Most women present with advanced disease with little prospect for cure. There have been some advances in surgical and chemotherapeutic strategies, but these approaches have led to only minor improvements in outcome. There remains a significant risk for recurrence and resistance to therapy, and hence there is a need to improve upon the current treatment options. Molecularly directed therapy aims to target tumor cells and the tumor microenvironment by blocking specific molecular changes in the cancer. The most promising agents so far are the antiangiogenic agents and polyadenosine diphosphate-ribose polymerase inhibitors. This article reviews the various targeted therapeutic approaches under clinical investigation in ovarian cancer and the challenges facing their future success in the clinic..
Smith, I.E. & Banerjee, S.
(2009). The follow-up of women at high risk for breast cancer relapse. Breast,
Vol.18 Suppl 3,
Banerjee, S., Pancholi, S., A'hern, R., Ghazoui, Z., Smith, I.E., Dowsett, M. & Martin, L.-.
(2008). The effects of neoadjuvant anastrozole and tamoxifen on circulating vascular endothelial growth factor and soluble vascular endothelial growth factor receptor 1 in breast cancer. Clin cancer res,
PURPOSE: Vascular endothelial growth factor (VEGF) is a key angiogenic factor mediating neovascularization. Soluble VEGF receptor 1 (sVEGFR-1) is an intrinsic negative counterpart of VEGF signaling and the ratio of sVEGFR-1 to VEGF has been shown to be a prognostic factor. Estrogen-bound estrogen receptor enhances VEGF expression, providing a common link between these signaling pathways that may be targeted by endocrine therapy. We investigated the effects of anastrozole and tamoxifen over time on serum VEGF and sVEGFR-1. EXPERIMENTAL DESIGN: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) trial compared the preoperative use of anastrozole with tamoxifen in postmenopausal women with estrogen receptor-positive primary operable breast cancer over 12 weeks. Circulating VEGF and sVEGFR-1 were measured by ELISA in 106 patients treated with anastrozole or tamoxifen alone at baseline and after 2 and 12 weeks of treatment. RESULTS: The increase in serum VEGF from baseline to 12 weeks was significantly different between anastrozole and tamoxifen (anastrozole versus tamoxifen, 6% versus 38%; P = 0.047). There was a significant increase in sVEGFR-1 levels after 12 weeks of anastrozole (P = 0.037). The sVEGFR-1/VEGF ratio significantly decreased in the tamoxifen arm (P = 0.013) and the change in sVEGFR-1/VEGF ratio from baseline to 12 weeks was significantly different between anastrozole and tamoxifen (anastrozole versus tamoxifen, 24% increase versus 34% decrease; P = 0.013). CONCLUSIONS: Treatment with anastrozole and tamoxifen resulted in differential effects on serum angiogenic markers. This may be related to the relative effectiveness of the treatments. These data provide further support for cross talk between estrogen receptor and VEGF..
Pancholi, S., Lykkesfeldt, A.E., Hilmi, C., Banerjee, S., Leary, A., Drury, S., Johnston, S., Dowsett, M. & Martin, L.-.
(2008). ERBB2 influences the subcellular localization of the estrogen receptor in tamoxifen-resistant MCF-7 cells leading to the activation of AKT and RPS6KA2. Endocr relat cancer,
Acquired resistance to endocrine therapies remains a major clinical obstacle in hormone-sensitive breast tumors. We used an MCF-7 breast tumor cell line (Tam(R)-1) resistant to tamoxifen to investigate this mechanism. We demonstrate that Tam(R)-1 express elevated levels of phosphorylated AKT and MAPK3/1-activated RPS6KA2 compared with the parental MCF-7 cell line (MCF-7). There was no change in the level of total ESR between the two cell lines; however, the Tam(R)-1 cells had increased phosphorylation of ESR1 ser(167). SiRNA blockade of AKT or MAPK3/1 had little effect on ESR1 ser(167) phosphorylation, but a combination of the two siRNAs abrogated this. Co-localization studies revealed an association between ERBB2 and ESR1 in the Tam(R)-1 but not MCF-7 cells. ESR1 was redistributed to extranuclear sites in Tam(R)-1 and was less transcriptionally competent compared with MCF-7 suggesting that nuclear ESR1 activity was suppressed in Tam(R)-1. Tamoxifen resistance in the Tam(R)-1 cells could be partially overcome by the ERBB2 inhibitor AG825 in combination with tamoxifen, and this was associated with re-localization of ESR1 to the nucleus. These data demonstrate that tamoxifen-resistant cells have the ability to switch between ERBB2 or ESR1 pathways promoting cell growth and that pharmacological inhibition of ERBB2 may be a therapeutic strategy for overcoming tamoxifen resistance..
Banerjee, S., Dowsett, M., Ashworth, A. & Martin, L.-.
(2007). Mechanisms of disease: angiogenesis and the management of breast cancer. Nat clin pract oncol,
Demonstration of the clinically significant activity of bevacizumab in breast cancer has attracted a great deal of interest. Numerous other antiangiogenic treatments are in clinical development and some established therapies including tamoxifen and trastuzumab might function, in part, by suppressing angiogenesis. In this Review, we discuss the potential of various components of the angiogenic pathway as prognostic and predictive factors in breast cancer. In addition, we describe existing clinical trials of antiangiogenic agents and the challenges facing the clinical development and optimum use of these agents for the treatment of breast cancer..
Banerjee, S., Reis-Filho, J.S., Ashley, S., Steele, D., Ashworth, A., Lakhani, S.R. & Smith, I.E.
(2006). Basal-like breast carcinomas: clinical outcome and response to chemotherapy. J clin pathol,
BACKGROUND: Grade-III invasive ductal carcinomas of no special type (IDCs-NST) constitute a heterogeneous group of tumours with different clinical behaviour and response to chemotherapy. As many as 25% of all grade-III IDCs-NST are known to harbour a basal-like phenotype, as defined by gene expression profiling or immunohistochemistry for basal cytokeratins. Patients with basal-like breast carcinomas (BLBC) are reported to have a shorter disease-free and overall survival. MATERIAL AND METHODS: A retrospective analysis of 49 patients with BLBC (as defined by basal cytokeratin expression) and 49 controls matched for age, nodal status and grade was carried out. Histological features, immunohistochemical findings for oestrogen receptor (ER), progesterone receptor (PgR) and HER2, and clinical outcome and survival after adjuvant chemotherapy were compared between the two groups. RESULTS: It was more likely for patients with BLBCs to be found negative for ER (p<0.0001), PgR (p<0.0001) and HER2 (p<0.01) than controls. Patients with BLBCs were found to have a significantly higher recurrence rate (p<0.05) and were associated with significantly shorter disease-free and overall survival (both p<0.05). In the group of patients who received anthracycline-based adjuvant chemotherapy (BLBC group, n = 47; controls, n = 49), both disease-free and overall survival were found to be significantly shorter in the BLBC group (p<0.05). CONCLUSIONS: BLBCs are a distinct clinical and pathological entity, characterised by high nuclear grade, lack of hormone receptors and HER2 expression and a more aggressive clinical course. Standard adjuvant chemotherapy seems to be less effective in these tumours and new therapeutic approaches are indicated..
Banerjee, S., Reis, J.S., Ashley, S., Steele, D., Ashworth, A., Lakhani, S.R. & Smith, I.E.
(2006). Basal-like breast carcinomas: clinical outcome and response to chemotherapy. J clin pathol,
Background: Grade-III invasive ductal carcinomas of no special type (IDCs-NST) constitute a heterogeneous group of tumours with different clinical behaviour and response to chemotherapy. As many as 25% of all grade-III IDCs-NST are known to harbour a basal-like phenotype, as defined by gene expression profiling or immunohistochemistry for basal cytokeratins. Patients with basal-like breast carcinomas (BLBC) are reported to have a shorter disease-free and overall survival.Material and methods: A retrospective analysis of 49 patients with BLBC (as defined by basal cytokeratin expression) and 49 controls matched for age, nodal status and grade was carried out. Histological features, immunohistochemical findings for oestrogen receptor (ER), progesterone receptor (PgR) and HER2, and clinical outcome and survival after adjuvant chemotherapy were compared between the two groups.Results: It was more likely for patients with BLBCs to be found negative for ER (p < 0.0001), PgR (p < 0.0001) and HER2 (p < 0.01) than controls. Patients with BLBCs were found to have a significantly higher recurrence rate (p < 0.05) and were associated with significantly shorter disease-free and overall survival (both p, 0.05). In the group of patients who received anthracycline-based adjuvant chemotherapy (BLBC group, n = 47; controls, n = 49), both disease-free and overall survival were found to be significantly shorter in the BLBC group (p < 0.05).Conclusions: BLBCs are a distinct clinical and pathological entity, characterised by high nuclear grade, lack of hormone receptors and HER2 expression and a more aggressive clinical course. Standard adjuvant chemotherapy seems to be less effective in these tumours and new therapeutic approaches are indicated..
Lee, J.C., Banerjee, S. & King, D.M.
(2005). Breast or chest? A diagnostic conundrum. British journal of radiology,
Banerjee, S., Smith, I.E., Folkerd, L., Iqbal, J., Barker, P., Dowsett, M. & IMPACT trialists,
(2005). Comparative effects of anastrozole, tamoxifen alone and in combination on plasma lipids and bone-derived resorption during neoadjuvant therapy in the impact trial. Ann oncol,
BACKGROUND: Estrogen has beneficial effects on lipid metabolism and bone preservation. The IMPACT trial evaluated neoadjuvant therapy with anastrozole or tamoxifen alone, or a combination. The comparative effects of these treatments on serum lipids and bone resorption were assessed. PATIENTS AND METHODS: Non-fasting clotted blood samples were taken from 176 postmenopausal patients at baseline, 2 and 12 weeks for assessment of serum levels of estradiol, the bone resorption marker CTx and lipid profiles [total cholesterol (TC), high density lipoprotein cholesterol (HDL-C) and non-HDL cholesterol (N-HDL-C)]. RESULTS: After 12 weeks, tamoxifen was associated with a significant increase in HDL-C (26.5%), and a decrease in TC (6.5%) and N-HDL-C (12.3%). Anastrozole was associated with a significant increase in HDL-C (11.2%), and a non-significant increase in TC (2.9%) and N-HDL-C (3.4%), both of which were significantly different from tamoxifen. The combination was associated with a significant increase in HDL-C (9.4%), and a decrease in TC (10.9%) and N-HDL-C (13.9%). For tamoxifen and the combination, there were non-significant decreases in CTx compared with a significant increase (45.6%) with anastrozole. No correlation between serum estradiol and CTx was seen in any of the treatment groups. CONCLUSION: Anastrozole did not have a detrimental effect on lipid profiles following 3 months of therapy. There was a significant increase in CTx with anastrozole in contrast to tamoxifen..
Parton, M., Maisey, N., Banerjee, S., Harper-Wynne, C., Sumpter, K., Ashley, S., Eisen, T. & Obrien, M.
(2004). Gefitinib in patients with non-small cell lung cancer (NSCLC): The Royal Marsden experience. J clin oncol,
7099 Background: Gefitinib (Iressa), an inhibitor of the intracellular tyrosine kinase domain, has demonstrated useful activity in advanced pre-treated NSCLC (IDEAL I / II). The clinical efficacy of gefitinib was assessed as part of an Expanded Access Programme. METHODS: Patients (pts)were treated with gefitinib 250mg/day. Endpoints included overall survival (OS)and time to treatment failure (TTF). Objective and symptom response (OR, SR) were assessed at 1 month intervals. RESULTS: 140 patients were assessed: median age (range), 65 (35-88) years; male/female, 80/60; performance status (PS)0/1/2/3, 1/45/37/17%; advanced disease (IIIB/IV), 123pts; median number of prior chemotherapy regimens (range), 1 (0-4). 124 patients were evaluable for OR: partial responses (PR) 6%; stable disease (SD) 55%; progressive disease (PD) 39%. Median duration of disease control (PR + SD) was 13 weeks (95% CI 9-17). 130 patients were evaluable for SR: symptom improvement (SI) 30%; No change (NC)33%; worsening symptoms (WS) 37%. Median duration of symptom control (SI+NC) was 11 weeks (95% CI 9-13). The most common toxicity was diarrhoea (Grade 3: 4.5%; Grade IV: 1%). 1 patient died of suspected pneumonitis. Median OS and TTF was 20 weeks (95% CI 15-25) and 8 weeks (95% CI 7-9) respectively. Patients (n=12) with bronchoalveolar adenocarcinoma (BAC) had significantly longer TTF than adenocarcinoma and squamous-cell carcinoma (median duration was 13, 8 and 9 weeks respectively, p=0.04). OR and SI for patients with BAC was 9.1% and 50% respectively. Pts with a PS of 3 had significantly lower OS and TTF (8 and 5 weeks respectively), and OR and SI was 0% and 13.3% respectively. Number of prior chemotherapy regimens did not significantly alter survival. CONCLUSIONS: This large series of patients treated with gefitinib at 250mg/day, demonstrated similar survival and symptom response to published phase II data. Pts with BAC appeared to benefit more than other histological subtypes. Despite low toxicity, gefitinib does not benefit those with poor PS. However, gefitinib can benefit heavily pre-treated patients, since the number of prior chemotherapy regimens did not influence survival. No significant financial relationships to disclose..
George, A., Riddell, D., Seal, S., Talukdar, S., Mahamdallie, S., Ruark, E., Cloke, V., Slade, I., Kemp, Z., Gore, M., et al.
Implementing rapid, robust, cost-effective, patient-centred, routine genetic testing in ovarian Cancer Patients. Scientific reports,
Advances in DNA sequencing have made genetic testing fast and affordable, but limitations of testing processes are impeding realisation of patient benefits. Ovarian cancer exemplifies the potential value of genetic testing and the shortcomings of current pathways to access testing. Approximately 15% of ovarian cancer patients have a germline BRCA1 or BRCA2 mutation which has substantial implications for their personal management and that of their relatives. Unfortunately, in most countries, routine implementation of BRCA testing for ovarian cancer patients has been inconsistent and largely unsuccessful.
We developed a rapid, robust, mainstream genetic testing pathway in which testing is undertaken by the trained cancer team with cascade testing to relatives performed by the genetics team.
207 women with ovarian cancer were offered testing through the mainstream pathway. All accepted. 33 (16%) had a BRCA mutation. The result informed management of 79% (121/154) women with active disease. Patient and clinician feedback was very positive. The pathway offers a 4-fold reduction in time and 13-fold reduction in resource requirement compared to the conventional testing pathway.
The mainstream genetic testing pathway we present is effective, efficient and patient-centred. It can deliver rapid, robust, large-scale, cost-effective genetic testing of BRCA1 and BRCA2 and may serve as an exemplar for other genes and other diseases..
Yang, Y., Wu, L., Shu, X., Lu, Y., Shu, X.-., Cai, Q., Beeghly-Fadiel, A., Li, B., Ye, F., Berchuck, A., et al.
Genetic data from nearly 63,000 women of European descent predicts DNA methylation biomarkers and epithelial ovarian cancer risk. Cancer research,