Toxicity of high-dose radiotherapy combined with daily cisplatin in non-small cell lung cancer: results of the EORTC 08912 phase I/II study

The purpose of this work was to study the feasibility of concurrent chemora diation in patients with inoperable non-small cell lung cancer (NSCLC). 40 patients with inoperable NSCLC were treated with escalating doses of radiot herapy and cisplatin (cDDP). The radiation dose was increased step by step from 60.5 to 66 Gy in daily fractions of 2.75 Gy. Chemotherapy was also inc reased step by step from 20 to 24 daily doses of cDDP 6 mg/m(2) and given c oncurrently with radiotherapy. A dose of 40 Gy/2 Gy/20 fractions (fx) was g iven to the EPTV (elective planning target volume) which included the gross tumour volume with a margin of 2 cm and part of or the entire mediastinum. During each session a boost dose of 0.75 Gy was given simultaneously to th e BPTV (boost planning target volume), which encompassed the GTV (gross tum our volume) with a margin of 1 cm, for the first 20 fx, so the total dose t o the tumour was 55 Gy. Cisplatin 6 mg/m2 was given 1 h prior to radiothera py at each fraction. From then on the dose of radiation to the BPTV and the dose of cDDP were increased step by step. In group I the BPTV was irradiat ed with two extra fractions of 2.75 Gy to a total dose of 60.5 Gy without c DDP. In group II the same total dose of 60.5 Cy was given but the last two fractions were combined with cDDP. In group III four extra fractions of 2.7 5 Gy were given to the BPTV to a total dose of 66 Gy, only two of these fra ctions combined with cDDP. Finally, in group IV a total dose of 66 Gy was g iven in 24 fractions, all fractions combined with cDDP. All patients were p lanned by means of a CT-based conformal treatment planning. The maximal len gth of the oesophagus receiving greater than or equal to 60.5 Gy was 11 cm. 40 patients were evaluable for acute and late toxicity and for survival. A cute toxicity grade greater than or equal to 3 (common toxicity criteria, C TC) was rarely observed; nausea/vomiting in 3 patients (8%), leucopenia in 2 patients (5%), thrombocytopenia in 2 patients (5%), whilst 2 patients (5% ) suffered from severe weight loss. Late side-effects (European Organizatio n for Research and Treatment of Cancer/Radiation Therapy Oncology Group, EO RTC/RTOG) were: oesophageal toxicity greater than or equal to grade 3 in 2 patients (5%) and radiation pneumonitis grades 1 (3%) and 2 (3%) in 1 patie nt each. Overall actuarial 1- and 2-year survival was 53% and 40%, respecti vely. The 1- and 2-year local disease-free interval was 65% and 58% respect ively. Radiotherapy at a dose of 66 Gy/2.75 Gy/24 fx combined with daily cD DP 6 mg/m(2) given over 5 weeks is feasible and results in a good local dis ease-free interval and a good survival rate. This treatment schedule is at present being tested as one of the two treatment arms of EORTC phase III st udy protocol 08972/22973. (C) 2000 Elsevier Science Ltd. All rights reserve d.