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Topotecan Active as First-Line Combination Therapy for Advanced Non-Small-Cell Lung Cancer

Topotecan Active as First-Line Combination Therapy for Advanced Non-Small-Cell Lung Cancer

A new study presented at the Ninth World Congress on Lung Cancer demonstrated that topotecan (Hycamtin) in combination with carboplatin (Paraplatin) is active as a first-line treatment of advanced non-small-cell lung cancer. Topotecan is not currently approved for the treatment of patients with non-small-cell lung cancer.

The noncomparative, multicenter study, conducted by L’Hopital Arnaud de Villeneuve, in conjunction with SmithKline Beecham, evaluated the activity of topotecan in combination with carboplatin in chemotherapy-naive patients. Results from the investigation indicate that the combination produced an overall response rate of 14% in evaluable patients, with 49% achieving an arrest in tumor progression.

"These results indicate that topotecan is active in solid tumors other than ovarian and small-cell lung cancer," said Jean-Louis Pujol, MD, L’Hôpital Arnaud de Villeneuve, Montpellier, France. "They also underscore the fact that combination treatment with topotecan may offer patients with non-small-cell lung cancer an additional therapeutic option."

Activity of Topotecan

In this phase II trial, 47 chemotherapy-naive, non-small-cell lung cancer patients were treated with IV topotecan 0.5 mg/m2 daily for 5 days, with an area under the concentration-time curve (AUC) 5 dose of carboplatin administered on the first day of treatment. The regimen was repeated every 21 days. Patients received a median of four courses of treatment; reductions and escalations in the dose of topotecan were based on the incidence of toxicity and/or adverse events.

Of the 42 patients who were evaluable for efficacy, 14% achieved an objective response (one complete response, five partial responses). Stable disease that lasted at least 56 days was reported in 36% of patients (n = 17). When the overall response and stable disease rates were combined, 49% of patients achieved an arrest in tumor progression. The median duration of response was 16 weeks, with a median survival of 32.7 weeks.

"The study results are interesting in light of the Eastern Cooperative Oncology Group (ECOG) 1594 study comparing three front-line non-small-cell lung cancer regimens to the standard of care that was presented at ASCO [American Society of Clinical Oncology] this spring [2000], where the median survival across the four regimens ranged from 31 to 36 weeks," said Dr. Pujol.

Hematologic toxicities were the most frequent adverse events, but were reversible in most patients. The most common hematologic events included grade 3/4 anemia in 36% of patients, neutropenia in 53%, and thrombocytopenia in 58%. Nonhematologic events included asthenia in 11% of patients, dyspnea in 6%, and infection in 6%. These toxicities were mild or moderate in severity and manageable with the usual methods of supportive care.

Additional Data

Additional presentations at the Ninth World Congress on Lung Cancer included a phase I/II study that evaluated the activity of oral topotecan in combination with either paclitaxel (Taxol) or cisplatin (Platinol) in the treatment of chemotherapy-naive patients with non-small-cell lung cancer. According to data from the phase I trial, oral topotecan in combination with paclitaxel produced an overall response rate of 12% (n = 33) in patients who were evaluable for response. Further, 27% of the treated patients achieved stable disease lasting at least 56 days.

The investigators noted that it was premature to evaluate survival. Grade 3 and 4 hematologic toxicities included neutropenia and anemia, which were reported in 68% and 18% of patients, respectively. The most frequent grade 3 and 4 nonhematologic toxicities included dyspnea (17%), nausea (12%), and vomiting (12%) at the maximum tolerated dose.

Phase II Study

In the phase II study of 50 patients, 28% (n = 14) of those treated with oral topotecan and cisplatin achieved a partial response, while 16% (n = 8) experienced disease stabilization that lasted more than 56 days. In this study, the median survival was 35.4 weeks. The most common adverse events included grade 3/4 neutropenia, anemia, and thrombocytopenia in 70%, 48%, and 46% of patients, respectively. All of the nonhematologic toxicities were mild or moderate and manageable and included vomiting (27%), anorexia (20%), and diarrhea (20%).

"These data illustrate that oral topotecan in combination with paclitaxel or cisplatin produces activity with acceptable tolerability and an acceptable androgen-receptor profile," said Professor Torben Palshof, MD, Arhus Kommunehospital, Copenhagen, Denmark. "These results, together with those of the topotecan and carboplatin study, indicate that topotecan has the potential to provide patients with an additional therapeutic option. Further, the 56-day sustained disease stabilization observed in these trials bodes well for the use of topotecan in this treatment population."

Studies assessing the safety and efficacy of oral topotecan in various tumor types are currently ongoing.

 
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