Weekly irinotecan and cisplatin in advanced non-small cell lung cancer: A multicenter phase II study

The combination of weekly irinotecan (CPT-11) and monthly cisplatin has sho wn promising activity in advanced non-small cell lung cancer (NSCLC) in pre vious Phase I and II studies. However, same-day administration of these age nts may better exploit their therapeutic synergy and minimize toxicities. T his multicenter Phase II study was undertaken to evaluate the efficacy and safety of a combination of weekly CPT-11 and weekly cisplatin in patients w ith advanced NSCLC, Patients with chemotherapy-naive stage IIIB or IV NSCLC were treated with repeated cycles of therapy comprising weekly treatment w ith both cisplatin and CPT-11 for 4 weeks, followed by a 2-week rest. The s tarting doses of CPT-11 and cisplatin were 65 and 30 mg/m(2), respectively. Treatment was continued until the occurrence of disease progression, unacc eptable toxicity, or a maximum of six cycles. Fifty patients were enrolled. The median age was 59 years (range, 44-79 years). Eastern Cooperative Onco logy Group performance status was 0 in 22 patients, 1 in 19 patients, and 2 in 9 patients. Seven and 43 patients had stages IIIB and IV disease, respe ctively. Five patients had brain metastasis, Patients received a median of three 6-week cycles (range, 1-6), The objective response rate was 36% (18 o f 50; 95% confidence interval, 24-54%) and included 18 partial responses. M edian time to tumor progression was 6.9 months (range, 0.6-15.2), The media n survival was 11.6 months (range, 0.16-21.9 months), and the 1-year surviv al rate was 46%, Grade 3/4 nonhematological toxicities included vomiting (1 2%) and diarrhea (26%), Grade 3/4 hematological toxicities included anemia (14%), neutropenia (26%), and thrombocytopenia (14%), Relative dose intensi ties for CPT-II and cisplatin were 89 and 62%, respectively. Weekly combine d administration of CPT-11 and cisplatin achieved a promising overall respo nse rate, median time to tumor progression, and median survival in patients with stage IIIB/IV NSCLC, The regimen was well tolerated, and the planned dose intensity was well maintained. Further evaluation of this combination in NSCLC is warranted.