Oral Hycamtin gets FDA approval for relapsed SCLC

ROCKVILLE, Maryland—The FDA has approved GlaxoSmithKline's oral Hycamtin (topotecan) capsules for the treatment of relapsed small-cell lung cancer (SCLC). Specifically, Hycamtin 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.

Hycamtin capsules are the only oral single-agent chemotherapy approved for the treatment of SCLC after failure of first-line therapy. The product will be available in 2008, the company said.

"The approval of Hycamtin capsules is particularly important for patients with relapsed small-cell lung cancer as they now have an effective treatment option that has been shown to provide a survival benefit and can be conveniently taken at home," said Debasish Roychowdhury, MD, vice president, Global Clinical Development, Oncology Medicine Development Center, GSK. "Additionally, this milestone underscores GSK Oncology's commitment to helping improve cancer patients' quality of life."

This approval was based on positive results from a phase III study comparing Hycamtin capsules plus best supportive care (BSC) to BSC alone in patients with relapsed SCLC, in addition to phase II and phase III supporting studies.

In the pivotal phase III clinical trial, Hycamtin capsules added to BSC were associated with prolonged survival in patients with relapsed SCLC. This was the first randomized study ever to demonstrate that patients with relapsed SCLC live longer when they are treated with BSC and chemotherapy, compared to BSC alone, the company said.

Study results were published in the December 1, 2006, issue of the Journal of Clinical Oncology (24:5441-447, 2006).

"In clinical trials, Hycamtin capsules have shown the potential to benefit patients with SCLC, many of whom are prone to relapse," said John Eckardt, MD, director of clinical research for the Center for Cancer Care and Research, St. Louis. "The approval of Hycamtin capsules opens up new possibilities for patients battling this disease and provides a convenient alternative to IV therapy."

In the phase III multicenter trial, 141 patients with relapsed SCLC not considered as candidates for standard IV therapy were randomized to receive BSC alone (n = 70) or Hycamtin capsules, 2.3 mg/m²/d, days 1 through 5, every 21 days, plus BSC (n = 71). The primary objective was to compare overall survival between the two treatment arms.

Patients who received Hycamtin capsules plus BSC showed a statistically significant improvement in overall survival, compared with the patients who received BSC alone (Log-rank P = .0104). Median survival with Hycamtin capsules plus BSC was 25.9 weeks vs 13.9 weeks with BSC alone. The hazard ratio was 0.64, indicating a 36% reduction in the risk of death for patients who received Hycamtin capsules/BSC, compared with the patients who received BSC alone.

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

Oral Hycamtin is a topoisomerase I (topo-I) inhibitor. Topo-I is a naturally produced protein essential for cell division in both normal and cancer cells. Interaction between topo-I and Hycamtin capsules results in permanent damage to the cell's genetic material and the death of dividing cells.