Preclincal and clinical experience with cisplatin and carboplatin and simultaneous radiation in non-small cell lung cancer

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Abstract
Preclinical experiments with cisplatin and carboplatin showed radiosensitizing capability for these drugs against non-small cell lung cancer (NSCLC) cell lines and phase II clinical investigations were undertaken in pa tients with stage IIIA/B NSCLC. In the first trial, cisplatin 20 mg/M2 was infused on the first day of every treatment week, followed in about 1 hour by radiotherapy. Radiotherapy was given in single daily 2-Gy doses 5 days a week for 3 weeks, and, after a 2-week interval, for an additional 2 weeks. There were 5 complete responses (CRs) and 15 partial responses (PRs), while 6 patients had no change and 4 progressive dis ease, for a 67% overall response. Median survival was 14 months; the 2-year survival rate was 20%. To investigate the maximum tolerated dose of carboplatin, escalating doses were given on day 1 of each treatment week; simultaneous radiotherapy was administered as in the cisplatin study. Drug doses began at 100 mg/m2 and were increased by increments of 10 or 20 mg/m2 to a maximum of 200 mg/m2 with 5 pa tients treated at each dose level. Dose escalation was to stop when 3 of 5 patients developed intolerable World Health Organization (WHO) grade 3 rnyelosuppression. No grade 3 or 4 leukopenia occurred at carboplatin doses 140 mg/m2 Grade 3 leukopenia was seen in only 1 patient from the groups receiving 150, 160, or 180 mg/m2 Of the 35 patients evaluable thus far, 1 achieved CR and 18 PR, while 10 had no change and 6 progressive disease despite treatment, for a 54% overall response rate. Response rate in patients with stage IIIB disease was 48%. When responses were classified according to low- (100 to 130 mg/m2 or high-dose (140 to 180 mg/m2 treatment, the high-dose group had a higher re sponse rate (75% vs. 48%). Median overall survival is 10 months.