A PHASE-III STUDY OF ACCELERATED RADIOTHERAPY WITH AND WITHOUT CARBOPLATIN IN NONSMALL CELL LUNG-CANCER - AN INTERIM TOXICITY ANALYSIS OF THE FIRST 100 PATIENTS

Purpose: In 1989 we initiated a multicenter randomized trial to determ ine if accelerated radiotherapy with or without concurrent carboplatin improves local control and survival in patients with limited nonsmall cell lung cancer. This interim analysis was performed on the first 10 0 patients to determine whether the toxicity of the four treatment arm s is acceptable. Methods and Materials: One hundred patients with limi ted nonsmall cell lung cancer have been randomized to receive one of f our treatments: arm I, radiotherapy 60 Gray (Gy) in 30 fractions in 6 weeks; arm II, accelerated radiotherapy 60 Gy in 30 fractions in 3 wee ks; arm III, radiotherapy as in arm I plus carboplatin 350 mg/m(2) dur ing weeks 1 and 5 of radiotherapy; arm IV, radiotherapy as in arm II p lus carboplatin 350mg/m(2) during week 1. Survival was measured for th e group as a whole and treatment-related toxicities in the four arms w ere compared. Results: The estimated median survival for all 100 patie nts was 17.1 months with 33% estimated survival at 2 years, The major toxicities were hematologic and esophageal, Patients receiving carbopl atin had more neutropenia (p < 0.0001) and thrombocytopenia (p = 0.002 ) than patients receiving radiotherapy alone, and this was most marked in patients on arm III, Both carboplatin and accelerated radiotherapy separately caused more severe esophagitis when compared to convention al radiotherapy alone (p = 0.011 and p = 0.0017, respectively). Esopha gitis was more prolonged in patients having accelerated radiotherapy ( p < 0.0001, median duration 3.2 months compared with 1.4 months for pa tients receiving conventional fractionation), Six patients (23%) treat ed on arm II have required dilatation of esophageal stricture, one dyi ng with a laryngo-esophageal fistula. Conclusion: In patients receivin g radiotherapy for unresectable lung cancer, overall treatment time ca n be halved and carboplatin administered concurrently with increased b ut acceptable esophageal and hematologic toxicity.