Herpes Virus to Potentially Treat Head and Neck Cancer Patients
30 July 2010 - Worldwide, around 650,000 people are diagnosed with squamous cell cancer of the head and neck each year, and around 350,000 die from the disease annually. Locally advanced disease (stage III/IV) requires treatment with radiotherapy and concomitant chemotherapy. Even with intensive treatment, 35–55% of patients develop a local manifestation of the tumour, or metastatic (where the cancer spreads to other parts of the body) recurrence within two years. Therefore, new treatments that improve local control of the cancer are needed.
A genetically engineered cold sore virus (herpes simplex virus) has recently been used to treat head and neck cancer patients in a Phase I/II clinical trial run by The Institute of Cancer Research (ICR) and The Royal Marsden NHS Foundation Trust (The Royal Marsden). The modified herpes simplex virus, known as OncoVEX, has the potential to enhance the therapeutic activity of conventional anti-cancer therapies, including radiation and chemotherapy. OncoVEX acts by multiplying inside cancer cells, but not healthy cells. Once OncoVEX enters the cancer cells, it causes the cell to produce a protein called granulocyte-macrophage colony-stimulating factor (GM-CSF). The cancer cells rupture to release the replicated virus, GM-CSF and tumour specific antigens (TSAs), which helps to stimulate the patients’ immune system.
The study was conducted in patients who were newly diagnosed for stage III/IV squamous cell cancer of the head and neck. One of the purposes of the study was to determine the recommended dose of OncoVEX for future studies. Therefore, patients received injections of OncoVEX in a dose escalation into their cancer-affected lymph nodes – radiotherapy and chemotherapy were given at the same time. Assessments included anti-tumour activity and relapse rates.
Seventeen patients were treated. Head and neck tumour shrinkage could be seen on scans for 14 patients (82%), while 93% of patients had no trace of residual cancer in their lymph nodes during subsequent surgery to remove them. Only two of 13 patients given the virus treatment at a high dose relapsed. Localised tumour control was achieved in all patients, with 76.5% being relapse-free so far. “Around 35–55% of patients given the standard chemotherapy and radiotherapy treatment typically relapse within two years, so these results compare very favourably,” Principal Investigator Dr Kevin Harrington from the ICR and The Royal Marsden says. “This was a small study so the results should be interpreted with caution; however the very high rates of tumour response have led to the decision to take this drug into a large scale Phase III trial. This will be the first ever phase III trial combining virus therapy with curative chemoradiation.” Side-effects were generally mild to moderate, and most were thought to be due to the chemotherapy or radiotherapy. OncoVEX has previously shown promising results when administered on its own in early stage trials of patients with other cancer types, including a Phase II trial of metastatic melanoma patients. “This trial showed for the first time that these oncolytic viruses can be safely used in combination with other cancer treatments given with the intention of curing patients,” Dr Harrington says.