Topotecan hydrochloride (Hycamtin), as a single agent or in combination with other agents, may offer a new treatment option for people suffering from small-cell lung cancer, according to results from five clinical trials reviewed at the 15th Annual Meeting of the Chemotherapy Foundation in New York City. Topotecan, which is approved in the United States for the treatment of patients with recurrent, metastatic ovarian cancer, is not currently indicated for the treatment of small-cell lung cancer.
Since survival rates of patients with small-cell lung cancer have traditionally been poor and results with many other drugs have been very disappointing, it is critical that we identify new agents that can be used as either first or second-line therapy, said Dr. David S. Ettinger, professor of oncology and medicine and associate director for clinical affairs, Johns Hopkins Oncology Center, who presented the review. Results from several studies suggest that Hycamtin, either alone or in combination with other agents, may be a promising treatment option for this patient population.
According to Dr. Ettinger, preliminary results from a new phase II trial sponsored by the North Central Cancer Treatment Group showed that patients who received a combination of topotecan and paclitaxel (Taxol) with granulocyte-colony stimulating factor (G-CSF
[Neupogen]) achieved response rates consistent with those observed with currently used first-line chemotherapies. In this small study by Jett and colleagues, 15 patients with previously untreated small-cell lung cancer received topotecan (1 mg/m2 as a 30-minute infusion for 5 consecutive days) and paclitaxel (135 mg/m2 administered on day 5 as a 24-hour infusion) over 3 weeks. In the 12 patients evaluable for response, the overall response rate was 92%, with 2 patients achieving a complete response and 9 patients achieving a partial response. The 1-year survival-rate was 50%.
In another study conducted by the Eastern Cooperative Oncology Group, Schiller and associates treated 48 patients with previously untreated, extensive-disease small-cell lung cancer with a 2.0-mg/m2 infusion of topotecan as a single agent on days 1 through 5 every 3 weeks. Patients also received G-CSF. Nineteen (39%) patients had a partial response. The median response duration was 4.8 months, overall median survival time was 10 months, and the 1-year survival rate was 39%.
Because these studies involved a small number of patients, additional studies are needed to confirm these results.
Second-Line Single-Agent Therapy
Also presented in the review were studies indicating that topotecan alone is active in relapsed small-cell lung cancer. In an international, randomized, phase III clinical trial conducted by Schiller et al, topotecan showed comparable activity to cyclophosphamide, Adriamycin, and vincristine (CAV) in the treatment of relapsed small-cell lung cancer patients. A total of 125 patients were randomized to receive either topotecan (1.5 mg/m2 as a 30-minute infusion once daily for 5 days) or CAV by infusion on day 1 every 3 weeks. Patients treated with topotecan achieved a 25% response rate vs 15% for patients treated with CAVa nonsignificant difference. The median times to progression, median survival, and toxicity were similar for topotecan and CAV.
In one of the largest phase II clinical trials conducted to date with a single agent in the second-line treatment of this disease, nearly one-quarter of all eligible patients treated with topotecan alone achieved a complete or partial response. In this study, which was published by Ardizzoni et al earlier this year in the Journal of Clinical Oncology, 92 patients with small-cell lung cancer received a 30-minute infusion of topotecan (1.5 mg/m2) for 5 consecutive days every 3 weeks. All patients in the trial had received prior treatment with other antitumor agents.
The overall response rate was 22% (6.4% in refractory patients and 37.8% in patients sensitive to first-line chemotherapy). The median survival time for patients who responded to topotecan was 12.5 months, and the median survival time for all patients was 5.4 months.
In a separate study published by Perez-Soler et al in the Journal of Clinical Oncology, 28 previously treated patients who were refractory to etoposide (VePesid) and cisplatin (Platinol) received topotecan (1.25 mg/m2 intravenously for 5 days every 3 weeks). Eleven percent of the patients achieved a partial response The overall median survival time was 20 weeks.
These results are encouraging, because most small-cell lung cancer patients will eventually relapse and become very difficult to treat. Studies with Hycamtin as a single agent therapy have shown responses in patients who have already received first-line chemotherapy. In addition, patients who respond to Hycamtin have demonstrated longer than expected durations of response and survival, said Dr. Ettinger.