title: Weekly irinotecan and cisplatin in advanced non-small cell lung cancer: a multicenter phase II study.
abstract: 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/m2, 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.
authors.affiliation: Vanderbilt University, Nashville, Tennessee 37232, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Jagasia
authors.forename: C J
authors.initials: CJ
authors.lastname: Langer
authors.forename: D H
authors.initials: DH
authors.lastname: Johnson
authors.forename: F
authors.initials: F
authors.lastname: Yunus
authors.forename: J S
authors.initials: JS
authors.lastname: Rodgers
authors.forename: L L
authors.initials: LL
authors.lastname: Schlabach
authors.forename: A G
authors.initials: AG
authors.lastname: Cohen
authors.forename: Y
authors.initials: Y
authors.lastname: Shyr
authors.forename: D P
authors.initials: DP
authors.lastname: Carbone
authors.forename: R F
authors.initials: RF
authors.lastname: Devore
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D002945:Cisplatin / Q000008:administration & dosage; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin