Weekly Irinotecan and Cisplatin in Advanced Non-Small Cell Lung Cancer: A Multicenter Phase II Study

• Published in: Clinical cancer research 2001-01, Vol.7 (1), p.68-73
• Main Authors: JAGASIA, Madan H, LANGER, Corey J, JOHNSON, David H, YUNUS, Furhan, RODGERS, John S, SCHLABACH, Larry L, COHEN, Alan G, SHYR, Yu, CARBONE, David P, DEVORE, Russell F
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Camptothecin - administration & dosage; Camptothecin - analogs & derivatives; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - pathology; Carcinoma, Non-Small-Cell Lung - surgery; Chemotherapy; Cisplatin - administration & dosage; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - pathology; Lung Neoplasms - surgery; Male; Medical sciences; Middle Aged; Neoplasm Staging; Pharmacology. Drug treatments; Survival Analysis; Treatment Outcome
• ISSN: 1078-0432; 1557-3265

The combination of weekly irinotecan (CPT-11) and monthly cisplatin has shown promising activity in advanced non-small cell lung cancer (NSCLC) in previous Phase I and II studies. However, same-day administration of these agents may better exploit their therapeutic synergy and minimize toxicities. This multicenter Phase II study was undertaken to evaluate the efficacy and safety of a combination of weekly CPT-11 and weekly cisplatin in patients with advanced NSCLC. Patients with chemotherapy-naive stage IIIB or IV NSCLC were treated with repeated cycles of therapy comprising weekly treatment with both cisplatin and CPT-11 for 4 weeks, followed by a 2-week rest. The starting doses of CPT-11 and cisplatin were 65 and 30 mg/m 2 , respectively. Treatment was continued until the occurrence of disease progression, unacceptable toxicity, or a maximum of six cycles. Fifty patients were enrolled. The median age was 59 years (range, 44–79 years). Eastern Cooperative Oncology 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, respectively. Five patients had brain metastasis. Patients received a median of three 6-week cycles (range, 1–6). The objective response rate was 36% (18 of 50; 95% confidence interval, 24–54%) and included 18 partial responses. Median time to tumor progression was 6.9 months (range, 0.6–15.2). The median survival was 11.6 months (range, 0.16–21.9 months), and the 1-year survival rate was 46%. Grade 3/4 nonhematological toxicities included vomiting (12%) and diarrhea (26%). Grade 3/4 hematological toxicities included anemia (14%), neutropenia (26%), and thrombocytopenia (14%). Relative dose intensities for CPT-11 and cisplatin were 89 and 62%, respectively. Weekly combined administration of CPT-11 and cisplatin achieved a promising overall response 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.