Background: Irinotecan and cisplatin with concurrent radiotherapy is a powerful treatment combination for patients with limited-disease small-cell lung cancer (LD-SCLC). The objective was to determine the dose-limiting toxicity (DLT) and maximum-tolerated dose (MTD) of irinotecan and cisplatin with concurrent thoracic radiotherapy (TRT) as a once-every-three-weeks schedule. Patients and methods: Patients with LD-SCLC received a fixed-dose of irinotecan (340 mg) and cisplatin (135 mg) at day 1 in cycles 1 and 4. During cycles 2 and 3, irinotecan and cisplatin were given in a dose-escalation schedule with concurrent TRT (once daily, total dose 45Gray). Results: No DLT was observed at first two levels (irinotecan 100 mg or 120 mg and cisplatin 100 mg at day 1 of cycles 2 and 3). In the first five patients, four episodes of grade III diarrhoea/dehydration were observed at cycles 1 and 4. Therefore, from the sixth patient on, fixed-dose irinotecan at cycles 1 and 4 was reduced to 250 mg. At the subsequent level of irinotecan 140 mg and cisplatin 100 mg in cycles 2 and 3, two DLTs (severe oesophagitis and late vertebral radiation toxicity) were observed in one patient. Conclusion: Irinotecan 140 mg and cisplatin 100 mg with concurrent TRT was considered the MTD. Irinotecan and cisplatin in a once-every-three-weeks schedule is not recommended due to severe toxicity. Irinotecan may be more suited for intermittent weekly administration.

Additional Metadata
Keywords Cisplatin, Concurrent thoracic radiotherapy, Irinotecan, Limited-disease, Phase I study, Small-cell lung cancer
Persistent URL dx.doi.org/10.1016/j.lungcan.2007.11.010, hdl.handle.net/1765/29449
Citation
de Jong, W.K., de Jonge, M.J.A., van der Leest, A.H.D., van Meerbeeck, J.P., & Groen, H.J.M.. (2008). Irinotecan and cisplatin with concurrent thoracic radiotherapy in a once-every-three-weeks schedule in patients with limited-disease small-cell lung cancer: A phase I study. Lung Cancer, 61(1), 123–128. doi:10.1016/j.lungcan.2007.11.010