GlaxoSmithKline announced that the US Food and Drug Administration (FDA) approved Hycamtin (topotecan HCl) in combination with cisplatin, for the treatment of stage IV-B, recurrent, or persistent carcinoma of the cervix, which is not amenable to curative treatment with surgery and/or radiation therapy. Following a six-month priority review by the FDA, the expanded indication is based on phase III results that demonstrated a survival advantage by using Hycamtin in combination with cisplatin compared to cisplatin alone.

"Advanced cervical cancer can have a very poor prognosis, even with current treatments, so physicians are always looking for new and effective therapies," said Bradley Monk, M.D., Associate Professor, Division of Oncologic Gynaecology at University of California, Irvine. "These results show that Hycamtin extended the survival of these women, which is the ultimate goal."

The randomized, multicenter trial was designed and conducted by the Gynaecologic Oncology Group (GOG) and results were published last year in the Journal of Clinical Oncology. The study found that Hycamtin, in combination with cisplatin, was effective in treating cervical cancers which were not amenable to curative treatment with surgery and/or radiation therapy.

"The expanded use of Hycamtin in treating these patients with cervical cancer demonstrates GSK's ongoing commitment to bringing therapies to physicians for the treatment of women with cancer," said Kevin Lokay, Vice President of Oncology and Acute Care at GSK. "In addition to developing treatments, GSK is also developing therapies for the prevention of this disease. We are currently developing a vaccine for Human Papilloma Virus (HPV), the leading cause of cervical cancer."

The trial enrolled women with measurable, histologically-proven stage IVB, recurrent or persistent carcinoma of the cervix, who had recovered from the effects of prior surgery, radiation or chemoradiation. Patients were originally randomized into three arms: single-agent cisplatin (n=146, 50 mg/m2, every 21 days), Hycamtin plus cisplatin (n=147, Hycamtin 0.75 mg/m2, day 1-3 plus cisplatin 50 mg/m2 day 1 every 21 days), or MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin every 28 days). However, the MVAC arm was closed after 64 patients were enrolled, due to excessive toxicity.

The study showed a statistically significant improvement in overall survival for Hycamtin plus cisplatin arm (log-rank P=0.033). Median survival for Hycamtin plus cisplatin was 9.4 months when compared to 6.5 months for Cisplatin alone. This GOG study was led by Dr. Harry J. Long III, Professor of Oncology at Mayo Clinic College of Medicine in Rochester, Minn.

The Hycamtin plus cisplatin combination was generally well-tolerated. The most common dose-limiting toxicity was myelosuppression. Major hematologic adverse events (Grade 3 and 4) were more frequent in the combination arm than in the single-agent arm and included neutropenia (74% vs. 2%), thrombocytopenia (33% vs. 3%), Infection-febrile neutropenia (19% vs. 8%), respectively. The most common non-hematologic adverse events reported were constitutional*, Gastrointestinal, pain and metabolic toxicities.

Hycamtin is currently marketed in the United States by GlaxoSmithKline. It belongs to a class of drugs known as the topoisomerase I (topo-I) inhibitors. Topo-I is a naturally produced protein essential for cell division in both normal and cancer cells. Interaction between topo-I and Hycamtin results in permanent damage to the cell's genetic material and the death of dividing cancer cells. Hycamtin was originally approved for the treatment of small cell lung cancer sensitive disease after failure of first-line chemotherapy and for the treatment of metastatic carcinoma of the ovary after failure of initial or subsequent chemotherapy.