OSAKA, JapanAn 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 studys 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.
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
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.
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
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.