Phase I/II study of daily carboplatin, 5-fluorouracil and concurrent radiation therapy for locally advanced non-small-cell lung cancer.
A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities and the response rate of carboplatin and 5-fluorouracil administered daily with concurrent thoracic radiation therapy in patients with locally advanced non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, unresectable stage IIIA or IIIB non-small-cell lung cancer (NSCLC) were enrolled. Carboplatin (20-40 mg m(-2) 2-h infusion, daily) and 5-fluorouracil (200 mg m(-2) 24-h continuous infusion, daily) were administered concurrently with radiotherapy on days 1-33. Radiotherapy, with a total dose of 60 Gy, was delivered in 30 fractions on days 1-40. In the phase I portion, the daily dose of carboplatin was escalated from 20 to 40 mg m(-2). Once the maximum tolerated dose (MTD) and recommended dose (RD) of carboplatin was determined, the study entered the phase II portion. In the phase I portion, the daily MTD and RD of carboplatin were 40 and 35 mg m(-2), respectively. The dose-limiting toxicity was neutropenia. In the following phase II study, 30 patients were entered and the objective response rate was 76.7% (95% CI, 62-92%) and the local control rate was 85.7%. The median survival time was 19.8 months, with a survival rate of 70% at 1 year, 36.7% at 2 years. The major toxicities of treatment were neutropenia (>or=grade 3, 87.9%) and thrombocytopenia (>or=grade 3, 23.3%). This combined therapy for locally advanced non-small-cell lung cancer is promising and shows acceptable toxicity.
Yoshizawa
H
H
Division of Respiratory Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata 951-8510, Japan. nnys@med.niigata-u.ac.jp
Tanaka
J
J
Kagamu
H
H
Maruyama
Y
Y
Miyao
H
H
Ito
K
K
Sato
T
T
Iwashima
A
A
Suzuki
E
E
Gejyo
F
F
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000633:toxicity; D016190:Carboplatin / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000628:therapy*; D003131:Combined Modality Therapy; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D008175:Lung Neoplasms / Q000401:mortality / Q000628:therapy*; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local; D011838:Radiation-Sensitizing Agents / Q000008:administration & dosage* / Q000627:therapeutic use / Q000633:toxicity; D015996:Survival Rate
D011838:Radiation-Sensitizing Agents; D016190:Carboplatin; D005472:Fluorouracil