Alternated approach with local irradiation and combination chemotherapy including cisplatin or carboplatin plus epirubicin and etoposide in intermediate stage non-small cell lung cancer

Abstract

Prognosis of unresectable non-small cell lung cancer (NSCLC) patients is disappointing; their median survival time does not exceed 8-12 months. Recently, some authors reported an increased response rate and sometimes a prolonged survival for patients with intrathoracic disease treated with local irradiation combined with cytotoxic drugs. Fifty-eight consecutive patients with Stage IIIA or IIIB NSCLC were enrolled in a randomized Phase II trial of alternated treatment composed of four courses of combination chemotherapy and three cycles of local irradiation. Chemotherapy consisted of a randomly selected platinum compound (cisplatin [60 mg/m2] or carboplatin [300 mg/m2]) intravenously (i.v.) on Day 1, epirubicin (50 mg/m2) i.v. on Day 1, and etoposide (100 mg/m2) i.v. on Days 1-3. A course of radiotherapy consisted of 5 consecutive fractions (3 Gy per fraction, 1 fraction per day) for a total dosage of 15 Gy per course. Each course of chemotherapy was alternated every 2 weeks with a course of irradiation so that the entire treatment was performed in 13 weeks. Of the 58 patients, 53 were evaluable for response: 7 showed a complete clinical remission, and 25 reached a partial response, giving an overall response rate of 60% (95% confidence interval, 46%-74%). The tumors of four patients who showed a complete or partial response subsequently were surgically resected, and the complete disappearance of any residual tumor cells was documented histologically in two of them. No difference in response was observed between cisplatin- (16 of 26 [62%]) and carboplatin-treated patients (16 of 27 [59%]), and no correlation was found between response and either stage or histology. Patients enrolled in the carboplatin arm experienced less severe leukopenia and vomiting than did those in the cisplatin arm. Median freedom from progression and overall survival time were 28 and 39 weeks, respectively. Patients who responded had a significantly longer median duration of survival (49 weeks) as compared to non-responders (15 weeks). The alternated chemoradiotherapy treatment obtained a high response rate with substantial toxicity. This approach did not seem to improve the prognosis of patients significantly. In this setting, the administration of carboplatin instead of cisplatin appeared to be tolerated better by the patients.