Gynaecology Unit

Location: Royal Marsden

Section: NHS Clinical Research Programme

Head of Unit: Mr Desmond Barton, MD, FRCSEd, MRCOG, FACOG

Introduction

The Gynaecology Unit continues to make contributions to research questions across a range of diseases. In ovarian cancer, they mostly involve chemotherapy in advanced disease. Increasingly this includes patients whose disease has relapsed following first-line treatment, as data show that following relapse, patients can expect an extended survival period with further treatment. In endometrial cancer, an important national study is currently assessing the role of both radiotherapy and extended surgery after conventional hysterectomy. The Royal Marsden is one of the largest contributors to this trial. In surgery, we are also examining the role of lymph node dissection in the management of vulval cancer, and in radiotherapy we are examining patterns of bowel toxicity following treatment.

Interactions with the laboratory are a very important feature of our work, particularly those that help us to better understand why ovarian cancer cells become resistant to drug treatment and thus direct us towards improvements in chemotherapy. This latter work is conducted within The Institute’s Section of Medicine.

Relevance to the NHS Research and Development Programme

Gynaecological cancer comprises ovarian, cervical, endometrial, vaginal and vulva cancer, and together this represents a significant proportion of morbidity and mortality in women with cancer. Its management clearly requires a multidisciplinary team approach, and our clinical research programme is organised to reflect this. Specifically, it is structured around the South West London Cancer Network (Professor Stan Kaye is head of the Gynaecological Tumour Working Group). A portfolio of trials is being developed for each tumour type, and we already contribute a significant proportion of patients to NCRN approved trials, particularly in endometrial cancer.

Recent Highlights

• Successful completion of the feasibility trial (first-line treatment in ovarian cancer) incorporating carboplatin and docetaxel, with the epidermal growth factor receptor inhibitor, Tarceva
• Initiation and identification of maximum tolerated doses of two novel carboplatin-based schedules in relapsed ovarian cancer (capecitabine, epirubicin, carboplatin and epothilone 6, carboplatin)
• Nomination of BGC 945 – a novel alpha-folate receptor targeting drug – for clinical development. This agent should carry considerable specificity for ovarian cancer
• Highest UK contributor to the endometrial cancer trial 'ASTEC', which assesses the role of lymphadenectomy and post-operative radiotherapy
• Successful collection and storage in 96 cases of tumour cells from ascites (obtained from patients undergoing treatment for ovarian cancer) with agreement from Cancer Research UK to perform gene expression analyses for molecular markers of drug resistance
• In 2006 Professor Martin Gore was elected to the Council of the International Gynaecological Cancer Society and awarded the Felix Routledge Lectureship at the MD Anderson Cancer Centre, Houston. He has been appointed to NCI (US) Gynaecologic Cancer Study Committee and the Scientific Programme Committee of the American Society of Clinical Oncology (Gynecologic Track)

Future Aims

The clinical research programme over the next 2-3 years will increasingly reflect the multidisciplinary nature of the management of patients with all forms of gynaecological cancer. For example, in ovarian cancer, we will take part in studies assessing the optimal timing of surgery as part of primary treatment. Chemotherapy studies will include assessment of the role of new carboplatin combinations for patients with relapsed disease. In cervical cancer, we will play a leading role in initiating new studies optimising radiation therapy combined with other forms of treatment, as well as taking part in new chemotherapy trials in recurrent disease.

Within The Institute, and combined with the Section of Medicine, we will extend our translational research programme, which focuses on the collection of tumour material from patients with ovarian cancer. Through this, we aim to understand better the mechanisms underlying drug resistance. This will guide us towards better novel therapy, and our interaction with the Cancer Research UK Centre for Cancer Therapeutics will allow us to undertake early, proof of principle, clinical trials in patients with ovarian cancer, in our new Phase I clinical trials unit. These should include the first trial of the highly promising α-folate receptor targeted agent, BGC 945.