Etoposide plus cisplatin or carboplatin is first-line therapy for small cell lung cancer. However, up to 70% of patients become refractory to chemotherapy or relapse after treatment. In a Phase II trial, Japanese doctors are testing a combination of irinotecan (CPT-11) and cisplatin to treat these patients.

Previous work by the group has shown that the gastrointestinal side effects common with this combination can be decreased with oral alkalinization, which reduces reabsorption of the active CPT-11 metabolite from the gastrointestinal tract. This treatment, which involves oral administration of a combination of sodium bicarbonate, magnesium oxide, and pH neutral or basic water for four days after treatment with irinotecan/cisplatin, was applied in the current study.

The study enrolled 23 patients with small cell lung cancer who had relapsed after or were refractory to treatment with etoposide in combination with either cisplatin or carboplatin. The mean time off previous therapy was four months.

Partial responses occurred in 18 of the 22 patients for whom it was possible to evaluate response, yielding a response rate of 78%. Median survival was 251 days. One-year and two-year survival rates were 39% and 17% respectively.

Major toxicities were myelosuppression and diarrhea. Grade 3 diarrhea, however, occurred in only two patients (9%), comparing favorably with the 20% rate seen without oral alkalinization.

The results suggest that irinotecan/cisplatin is active against refractory or relapsed small cell lung cancer. Phase III studies of the combination are planned.