BETHESDA, Md--The FDA's Oncologic Drugs Advisory Committee (ODAC) has unanimously recommended approval of SmithKline Beecham's Hycamtin (topotecan HCl) for the treatment of patients with metastatic ovarian cancer after failure of initial or subsequent chemotherapy.
Hycamtin is the first topoisomerase I inhibitor to be recommended for approval in the United States. This new class of drugs kills cancer cells by inhibiting the enzyme toposiomerase I, which is essential in the replication of DNA.
At the ODAC hearing, Colin Broom, MD, of SmithKline Beecham, said that ovarian cancer is diagnosed in an estimated 26,700 women each year in the United States, and about 14,800 US women die annually from the disease. About 30% to 50% of women treated for ovarian cancer will relapse, with the recurring cancer often resistant to the original chemotherapy. Second-line drugs are then needed to treat the recurrence.
Dr. Eric Rowinsky, of Johns Hopkins Oncology Center, described three phase I trials examining safety and pharmacology. He said that the major toxicity of Hycamtin is hematological, particularly neutropenia. He noted that, based on these studies, a phase II dose was recommended and consistently used in all the trials.
Maurie Markman, MD, of the Cleveland Clinic Cancer Center, speaking in support of the new drug application (NDA), summarized the results of the phase I trial (039), an open, randomized, multicenter study that compared Hycamtin with Taxol (paclitaxel) in 226 women with recurrent ovarian cancer after first-line platinum therapy.
Patients were randomized to either a 30-minute IV infusion of Hycamtin, 1.5 mg/m²/day for 5 days, or to a 3-hour infusion of paclitaxel(Drug information on paclitaxel), 175 mg/m², every 21 days.
The objective response rate (complete response plus partial response) was 20.5% for Hycamtin vs 13.2% for paclitaxel, with a median duration of response of 32.1 weeks for Hycamtin vs 19.7 weeks for paclitaxel. The median time to progression was 23.1 weeks for Hycamtin vs 14 weeks for paclitaxel (P = .0021). Median survival was 61.3 weeks for Hycamtin vs 42.6 weeks for paclitaxel (P = .5153).