Weekly docetaxel and concomitant boost radiotherapy for non-small cell lung cancer. A phase I/II dose escalation trial

In this phase I/II study, we investigated the radiosensitising effects of docetaxel in non-small cell lung cancer (NSCLC). 30 patients with stage IIIb (18 patients) and IV (12 patients) NSCLC were treated with 64 Gy of accelerated chest radiotherapy (5-week schedule using a concomitant boost technique) and docetaxel on a weekly basis. The docetaxel starting dose level was 20 mg/m(2)/week and was escalated by 10 mg/m(2) increments in cohorts of 10 patients. Dose-limiting toxicity (grade 3 asthenia) was observed in 6 of 10 patients treated at the 40 mg/m(2)/week dose level, enforcing a 50% dose reduction in 4 patients. Grade 3 neutropenia was observed in 5 of 30 patients (17%), 3 of which were treated at the high dose level. Peripheral neuropathy occurred in 3 (10%) patients. A significant decrease in the absolute lymphocyte count was observed in all patients; the nadir was reached on day 28 (mean +/- standard deviation (S.D.) = 539 +/- 363/ml) compared with pretreatment values (mean +/- S.D. = 1842 +/- 863/ ml; P = 0.002). 6 out of 30 patients (20%) experienced grade 3 oesophagitis, resulting in a 1-2 week delay in overall treatment time. Complete response of the primary tumour was observed in 8 (27%) patients assessed 2 months after treatment. 4 of these patients had disease resistant to previous docetaxel-containing chemotherapy. A partial response occurred in 15 of 30 patients (50%) for an overall response rate of 77% (95% confidence interval (CI) 60-92%). Radiosensitisation with docetaxel is feasible and the recommended dose for further phase II studies is 30 mg/m(2)/week. Further phase II studies are required to confirm the remarkably high response rate observed in the present trial. (C) 1998 Elsevier Science Ltd. All rights reserved.