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 of 30% to nearly 90% in the untreated small-cell lung cancer population
ABSTRACT: There will be approximately 40,000 new cases of small-cell lungcancer this year. Prior to 1990, there were several agents with single-agentresponse rates of 30% to nearly 90% in the untreated small-cell lung cancerpopulation and approximately 10% to 20% in relapsed patients. During the 1990s,several new chemotherapy agents have displayed activity in small-cell lungcancer (paclitaxel [Taxol], gemcitabine [Gemzar], vinorelbine [Navelbine],topotecan [Hycamtin], and irinotecan [Camptosar, CPT-11]). The majority ofstudies with irinotecan have been conducted in Japan. The US experience islimited to a single multi-institution trial that was conducted in patients withpreviously treated small-cell lung cancer. A total of 44 patients were enteredin the study. Patients were stratified by response to prior therapy. Responsesoccurred in 7 of 44 patients for an overall response rate of 14%. The overallmedian survival was 4.8 months. [ONCOLOGY 15(Suppl 1):11-12, 2001]
There will be approximately40,000 new cases of small-celllung cancer this year. Prior to 1990, there were several agents withsingle-agent response rates in the untreated small-cell lung cancer populationof 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 allsmall-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 displayedactivity in small-cell lung cancer (paclitaxel [Taxol], gemcitabine [Gemzar],vinorelbine [Navelbine], topotecan [Hycamtin], and irinotecan [Camptosar,CPT-11]). A list of new agents is included in Table2.
In first- and second-line therapy studies in patients withsmall-cell lung cancer, response rates with irinotecan have ranged from 50% tobetween 14% and 47%, respectively. The majority of these studies with irinotecanwere conducted in Japan.
A recent randomized phase III trial (JCOG 9511) by the JapanClinical Oncology Group in 154 patients with extensive-stage small-cell lungcancer compared the combination of irinotecan and cisplatin (Platinol) tostandard 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% vs40%) were superior for patients in the irinotecan-containing arm. Confirmatoryphase III trials with the irinotecan/cisplatin combination are being planned inthe United States using both the Japanese regimen (irinotecan at 60 mg/m2 days1, 8, and 15, plus cisplatin at 60 mg/m2 day 1, every 4 weeks) and a regimen inwhich the schedule is modified to irinotecan at 65 mg/m2 days 1 and 8, pluscisplatin at 30 mg/m2 days 1 and 8, every 3 weeks.
The US experience thus far has been limited to a singlemulti-institution trial involving patients with previously treated small-celllung cancer.
A total of 44 patients were entered in this study, with patientstratification determined by response to prior therapy. Sensitive patients (n =17) previously achieved a complete response/partial response, and relapsedgreater 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 (onecourse). Treatment continued until disease progression. Patient characteristicswere as follows: median age, 60 years (range: 45 to 78 years); 68% males; andperformance status 60 to 70 (25%), 80 to 100 (75%).
Toxicities included two potentially drug-related deaths (sepsisand a central nervous system event). Hematologic toxicity was mild with 20%grade 3 neutropenia, 7% grade 4 neutropenia, and one episode of neutropenicfever (2.2%). Nonhematologic toxicity was also mild with grade 3/4 late diarrheaoccurring 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 treatmentfailure was 2.3 months (sensitive, 3.4 months; refractory, 1.3 months), andoverall 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 agentin patients with sensitive relapsed small-cell lung cancer. Studies ofirinotecan combinations in patients with previously untreated small-cell lungcancer are ongoing.
1. Noda K, Nishiwaki Y, Kawahara M, et al: Randomized phase IIIstudy of irinotecan (CPT-11) and cisplatin in extensive-disease small-cell lungcancer: Japan Clinical Oncology Group Study (JCOG9511) (abstract 1887). Proc AmSoc Clin Oncol 19:483a, 2000.
2. De Vore RF, Blanke CD, Denham CA, et al: Phase II study ofirinotecan (CPT-11) in patients with previously treated small-cell lung cancer(SCLC) (abstract 1736). Proc Am Soc Clin Oncol 17:451a, 1998.