FDA Approves Oral Agent for Relapsed Small-Cell Lung Cancer

PHILADELPHIA, Oct. 16 -- The FDA has approved topotecan (Hycamtin) capsules for treatment of relapsed small cell lung cancer (SCLC), GlaxoSmithKline has announced.

Specifically, the capsules are indicated for patients who had a complete or partial response to first-line chemotherapy and who are at least 45 days from the end of that treatment.

The company said topotecan capsules are the only oral single-agent chemotherapy approved for the treatment of SCLC after failure of first-line therapy.

This approval was based on a phase III study comparing topotecan capsules plus best supportive care to best supportive care alone in patients with relapsed SCLC who were not suitable candidates for IV therapy.

Seventy patients were randomized to topotecan capsules at 2.3 mg/m² /day, days one through five, every 21 days, plus best supportive care. They were compared with 71 controls.

Patients in the topotecan arm showed a statistically significant improvement in overall survival compared with the patients who received best supportive care alone (Log-rank P= 0.0104).

Median survival with topotecan capsules was 25.9 weeks (95% CI, 18.3 to 31.6) versus 13.9 weeks (95% CI, 11.1 to 18.6) in the control group. The hazard ratio was 0.64 (95% C.I: 0.45, 0.90), indicating a 36% reduction in the risk of death for patients who received topotecan capsules plus best supportive care compared with control patients.

John Eckardt, M.D., director of clinical research for the Center for Cancer Care and Research in St. Louis, who was an investigator in the GlaxoSmithKline -sponsored trials, said the approval of the capsules "provides a convenient alternative to IV therapy" and allows patients to receive chemotherapy in their own homes.

The most common Grade 3 or 4 hematologic adverse reactions with topotecan capsules were neutropenia (61%), anemia (25%), and thrombocytopenia (37%). The most common (>10%) non-hematologic adverse reactions (all grades) were nausea (27%), diarrhea (14%), vomiting (19%), fatigue (11%), and alopecia (10%).

Topotecan capsules belong to a class of drugs known as 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 topotecan capsules results in permanent damage to the cell's genetic material and the death of dividing cells.

GlaxoSmithKline said the capsules would be available in 2008.