Phase I/II study of weekly irinotecan and concurrent radiation therapy forlocally advanced non-small cell lung cancer

A study was undertaken to determine the maximum tolerated dose, the dose-li miting toxicities, and the response rate of irinotecan administered weekly with concurrent thoracic radiation therapy in patients with locally advance d non-small-cell lung cancer. In a phase I/II clinical trial, patients with histologically documented, surgically unresectable stage IIIA or IIIB non- small cell lung cancer (NSCLC) were enrolled. Irinotecan was administered a s a 90 min intravenous infusion once weekly for 6 weeks. The starting dose was 30 mg m(-2) and dose escalation was done in 15 mg m(-2) increments. Dos e-limiting toxicity was defined as grade 3 nonhaematologic toxicity (exclud ing nausea, vomiting and alopecia) or grade 4 haematologic toxicity accordi ng to the WHO criteria. Radiation was delivered to the primary tumour and r egional lymph nodes (40 Gy), followed by a boost to the primary tumour (20 Gy). Twenty-seven patients were entered into this study at three irinotecan dose levels (30, 45 and 60 mg m(-2)). Twenty-six eligible patients were ev aluated for toxic effects and clinical outcome. Severe oesophagitis, pneumo nitis, and diarrhoea occurred at 45 and 60 mg m(-2). Three of the five pati ents given 60 mg m(-2) developed grade 3 or 4 oesophagitis and pneumonitis. In addition, one patient died of pneumonitis after completing therapy at 4 5 mg m-2 in the phase II study. The objective response rate was 76.9% (95% CI, 53.0-88.9%). Oesophagitis, pneumonitis, and diarrhoea are the dose-limi ting toxicities of weekly irinotecan combined with thoracic irradiation. Th e maximum tolerated dose and the dose for the phase II study were 60 and 45 mg m(-2) wk(-1), respectively. This combined therapy for locally advanced non-small cell lung cancer is promising and shows acceptable toxicity.