Topotecan May Prove Useful as Second Line Treatment for SCLC

PARIS--Relapse after induction chemotherapy is a virtual inevitabilityin patients with small-cell lung cancer (SCLC), and response ratesto second-line chemotherapy have been generally disappointing.However, new study results presented at the Eighth Annual EuropeanCancer Conference (ECCO-8) suggest that topotecan, an investigationaltopoisomerase I inhibitor, may improve second-line results.

Dr. A. Ardizzoni of the National Cancer Research Institute, Genoa,reported results from the EORTC (European Organization for Researchand Treatment of Cancer) Early Clinical Trials Group and LungCancer Cooperative Group.

These data show that second-line treatment with topotecan yieldsresponse rates comparable to those achieved after first-line therapywith taxanes. This multicen-ter phase II study was the largesttrial ever conducted with a new drug in SCLC.

The new semisynthetic camptothecin analog was administered ina dose of 1.5 mg/m² infused over 30 minutes, on 5 consecutivedays every 3 weeks, for an average of four courses.

The heavily pretreated study population, more than a third ofwhom had also undergone radiotherapy, included 45 SCLC patientswho had relapsed more than 3 months after responding to first-linechemotherapy, and 49 patients who had been unresponsive to first-linetherapy or whose disease had progressed within 3 months of treatment.

The overall rate of response to topote-can approached 40% amongso-called sensitive patients, and was 7% in patients refractoryto induction chemotherapy. Response criteria were strict, Dr.Ardiz-zoni emphasized, with all responses assessed by CT scans,confirmed at 4 weeks, and reviewed by a study committee. By wayof comparison, he pointed out that response rates to second-linetreatment with etoposide (VePesid), doxorubicin, and cisplatin(Platinol) generally hover around 10% to 20%.

"The duration of response to topote-can was quite remarkableand was independent of whether the patient was refractory or sensitive,being 6 and 7.6 months, respectively," he said. This representsa doubling of the response duration usually documented with conventionalsecond-line therapy.

The development of severe leukopenia and neutropenia necessitateddose reductions in nearly a quarter of patients, and delayed upto 30% of treatment courses, Dr. Ardizzoni said. He observed,however, that nonhematologic side effects, such as nausea, vomiting,diarrhea, and muco-sitis, were rare and tended to be mild.

Dr. Ardizzoni urged further studies of topotecan in combinationwith other agents for both first- and second-line treatment ofSCLC.