title: Phase I/II trial of weekly cisplatin, etoposide, and irinotecan chemotherapy for metastatic lung cancer: JCOG 9507.
abstract: Combinations of cisplatin-irinotecan and cisplatin-etoposide are active and well tolerated in patients with both small-cell lung cancer (SCLC) and nonsmall-cell lung cancer (NSCLC). To define the recommended dose for phase II trials of irinotecan combined with cisplatin and etoposide in chemonaive patients with stage IV disease, 56 patients (11 having SCLC and 45 NSCLC) received cisplatin 25 mg m(-2) weekly for 9 weeks, etoposide 60 mg m(-2) for 3 days on weeks 1, 3, 5, 7 and 9, and irinotecan 20-100 mg m(-2) (levels 1-8) on weeks 2, 4, 6 and 8, together with a prophylactical granulocyte colony-stimulating factor support (50 microg m(-2) on days 4-7 on weeks 1, 3, 5, 7 and 9, and on days 2-7 on weeks 2, 4, 6 and 8). Grade 3-4 leukocytopenia, neutropenia and thrombocytopenia were noted in 20 (36%), 28 (50%) and nine (16%) patients, respectively. Grade 3 diarrhoea, grade 3 cardiac toxicity, and grade 4 transaminase elevation developed in one (1.8%) patient each. Totally, four of 56 patients were removed from the study because of toxicity and recovered, and two other patients died in situations where drug toxicity might contribute to their death. Dose-limiting toxicity was noted in less than one-third of patients at dose levels 1-7, but in all patients at dose level 8. Thus, the recommended dose was determined to be level 7 (irinotecan 90 mg m(-2)). The response rates for SCLC and NSCLC were 91% (10/11) and 38% (17/45), respectively. The median survival time and 1-year survival rate were 11.9 months and 46% for SCLC and 10.1 months and 40% for NSCLC, respectively. This regimen was considered to be feasible and promising for the treatment of stage IV SCLC and NSCLC.
authors.affiliation: Internal Medicine and Thoracic Oncology Division, National Cancer Center Hospital, Tsukiji 5-1-1, Chuo-ku, Tokyo, Japan. isekine@ncc.go.jp
authors.forename: I
authors.initials: I
authors.lastname: Sekine
authors.forename: Y
authors.initials: Y
authors.lastname: Nishiwaki
authors.forename: R
authors.initials: R
authors.lastname: Kakinuma
authors.forename: K
authors.initials: K
authors.lastname: Kubota
authors.forename: F
authors.initials: F
authors.lastname: Hojo
authors.forename: T
authors.initials: T
authors.lastname: Matsumoto
authors.forename: H
authors.initials: H
authors.lastname: Ohmatsu
authors.forename: K
authors.initials: K
authors.lastname: Goto
authors.forename: T
authors.initials: T
authors.lastname: Kodama
authors.forename: K
authors.initials: K
authors.lastname: Eguchi
authors.forename: T
authors.initials: T
authors.lastname: Shinkai
authors.forename: T
authors.initials: T
authors.lastname: Tamura
authors.forename: Y
authors.initials: Y
authors.lastname: Ohe
authors.forename: H
authors.initials: H
authors.lastname: Kunitoh
authors.forename: K
authors.initials: K
authors.lastname: Yoshimura
authors.forename: N
authors.initials: N
authors.lastname: Saijo
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; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage; D003967:Diarrhea / Q000139:chemically induced; D004305:Dose-Response Relationship, Drug; D005047:Etoposide / Q000008:administration & dosage; D005260:Female; D016179:Granulocyte Colony-Stimulating Factor / Q000008:administration & dosage; D006801:Humans; D007262:Infusions, Intravenous; D000077146:Irinotecan; D007970:Leukopenia / Q000139:chemically induced; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D013534:Survival; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D016179:Granulocyte Colony-Stimulating Factor; D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; D002166:Camptothecin