Summary
A study was undertaken to determine the maximum tolerated dose, the dose-limiting toxicities, and the response rate of irinotecan administered weekly with concurrent thoracic radiation therapy in patients with locally advanced 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 as 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. Dose-limiting toxicity was defined as grade 3 nonhaematologic toxicity (excluding nausea, vomiting and alopecia) or grade 4 haematologic toxicity according to the WHO criteria. Radiation was delivered to the primary tumour and regional 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 evaluated for toxic effects and clinical outcome. Severe oesophagitis, pneumonitis, and diarrhoea occurred at 45 and 60 mg m–2. Three of the five patients given 60 mg m–2 developed grade 3 or 4 oesophagitis and pneumonitis. In addition, one patient died of pneumonitis after completing therapy at 45 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-limiting toxicities of weekly irinotecan combined with thoracic irradiation. The 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.
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Takeda, K., Negoro, S., Kudoh, S. et al. Phase I/II study of weekly irinotecan and concurrent radiation therapy for locally advanced non-small cell lung cancer. Br J Cancer 79, 1462–1467 (1999). https://doi.org/10.1038/sj.bjc.6690233
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DOI: https://doi.org/10.1038/sj.bjc.6690233
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