Irinotecan/Etoposide Combination Achieves 65% Overall Response Rate

OSAKA, Japan—An overall response rate of 66% was achieved with a combination of irinotecan (Camptosar) and etoposide (VePesid) in patients with advanced small-cell lung cancer in a phase II study performed by the West Japan Thoracic Oncology Group. A final report on the study, conducted from 1995-98, was presented by Shinzoh Kudoh, MD, of Osaka City University School of Medicine.

The study was limited to patients with extensive-disease small-cell lung cancer who had not previously been treated with either chemotherapy or radiation. A total of 50 eligible patients were accrued. The 43 men and 7 women ranged in age from 28 to 73 years, with the mean being 65.

The performance status (PS) of most patients was good, Dr. Kudoh said, with 14 rated as PS 0, 33 as PS 1, and 3 as PS 2. Multiple metastases were identified in 20 of the patients and a single metastasis in 30.

The study’s dosage schedule was irinotecan 60 mg/m² on days 1, 8, and 15 and etoposide 80 mg/m² on days 2, 3, and 4. “This combination chemotherapy was repeated every 4 weeks for four cycles,” Dr. Kudoh explained.

Synergistic Effect

Irinotecan, also known as CPT-11, is a topoisomerase I inhibitor, while etoposide inhibits topoisomerase II. “Both agents have been shown to be active against small-cell lung cancer,” Dr. Kudoh noted. “In vitro, preclinical studies showed that sequential use of CPT-11 and etoposide had a synergistic effect against human cancer cell lines.” In addition, a phase I study of these agents in advanced lung cancer “showed promising antitumor activity.”

Encouraging Response Rate

In all, 33 of the 50 patients in the phase-II trial showed objective responses to the therapy, for an overall rate of 66%. Five (10%) had complete responses and 28 had partial responses. Three patients were still alive at the time of the meeting, Dr. Kudoh reported.

The median survival time was 11.5 months, he noted. The 1-year survival rate was 43.2% and the 2-year rate was 14.4%. Among the 33 patients who responded to the treatment, 11 had cancer recurrences at the primary pulmonary site and 7 in the brain. The median time to disease progression in the series was 5.9 months.

Mild Toxicity

“Toxicity was mild,” Dr. Kudoh said. The most common toxicity, he noted, was myleosuppression. Grades 3 and 4 neutropenia occurred in 62.9% of the patients, severe leukopenia in 28%, and anemia in 14%. “Only one patient experienced grade 3 diarrhea,” Dr. Kudoh pointed out, “and there were no treatment-related deaths.”

Myleosuppression was the major reason for reduction of the irinotecan doses, the investigator indicated. On day 8, the mean dosage was 49.8 mg/m² instead of the planned 60 mg/m², he said, and on day 15, 33.1 mg/m². The pronounced reduction on day 15, Dr. Kudoh noted, was 55.1% of the planned dose.

Nonetheless, Dr. Kudoh concluded that the irinotecan/etoposide combination is an active regimen against advanced small-cell lung cancer. “The advantage of this regimen,” he commented, “is that toxicity may be milder than with etoposide plus cisplatin.”