There will be approximately 40,000 new cases of small-cell lung cancer this year. Prior to 1990, there were several agents with single-agent response rates in the untreated small-cell lung cancer population of 30% to nearly 90% (see Table 1) and in relapsed patients of approximately 10% to 20%. Despite an initial sensitivity to chemotherapy, only 10% of all small-cell lung cancer patients will have significant long-term survival. Clearly, newer chemotherapy agents are needed for this disease.
During the 1990s, several new chemotherapy agents displayed activity in small-cell lung cancer (paclitaxel [Taxol], gemcitabine(Drug information on gemcitabine) [Gemzar], vinorelbine [Navelbine], topotecan(Drug information on topotecan) [Hycamtin], and irinotecan(Drug information on irinotecan) [Camptosar, CPT-11]). A list of new agents is included in Table 2.
In first- and second-line therapy studies in patients with small-cell lung cancer, response rates with irinotecan have ranged from 50% to between 14% and 47%, respectively. The majority of these studies with irinotecan were conducted in Japan.
A recent randomized phase III trial (JCOG 9511) by the Japan Clinical Oncology Group in 154 patients with extensive-stage small-cell lung cancer compared the combination of irinotecan and cisplatin(Drug information on cisplatin) (Platinol) to standard etoposide(Drug information on etoposide) and cisplatin. The overall response rate (89% vs 67%; P = .013), median survival (420 vs 300 days; P = .047), and 1-year survival (60% vs 40%) were superior for patients in the irinotecan-containing arm. Confirmatory phase III trials with the irinotecan/cisplatin combination are being planned in the United States using both the Japanese regimen (irinotecan at 60 mg/m2 days 1, 8, and 15, plus cisplatin at 60 mg/m2 day 1, every 4 weeks) and a regimen in which the schedule is modified to irinotecan at 65 mg/m2 days 1 and 8, plus cisplatin at 30 mg/m2 days 1 and 8, every 3 weeks.
The US experience thus far has been limited to a single multi-institution trial involving patients with previously treated small-cell lung cancer.
A total of 44 patients were entered in this study, with patient stratification determined by response to prior therapy. Sensitive patients (n = 17) previously achieved a complete response/partial response, and relapsed greater than 3 months after completion of initial therapy. All other patients (n = 27) were considered refractory. Treatment consisted of irinotecan at 125 mg/m2 (over 90 minutes) weekly for 4 weeks, followed by a 2-week rest period (one course). Treatment continued until disease progression. Patient characteristics were as follows: median age, 60 years (range: 45 to 78 years); 68% males; and performance status 60 to 70 (25%), 80 to 100 (75%).
Toxicities included two potentially drug-related deaths (sepsis and a central nervous system event). Hematologic toxicity was mild with 20% grade 3 neutropenia, 7% grade 4 neutropenia, and one episode of neutropenic fever (2.2%). Nonhematologic toxicity was also mild with grade 3/4 late diarrhea occurring in 26.6% of patients (see Table 3).
Responses were seen in seven patients (one complete response) for a response rate of 15.9%. Responses occurred in 6/17 sensitive patients (35.3%) and in 1/27 refractory patients (3.7%). Overall time to treatment failure was 2.3 months (sensitive, 3.4 months; refractory, 1.3 months), and overall survival was 4.8 months (sensitive, 5.9 months; refractory, 2.8 months). The results are presented in Table 4.
In conclusion, irinotecan is an active and well-tolerated agent in patients with sensitive relapsed small-cell lung cancer. Studies of irinotecan combinations in patients with previously untreated small-cell lung cancer are ongoing.