RAPIDLY ALTERNATING COMBINATION OF CISPLATIN-BASED CHEMOTHERAPY AND HYPERFRACTIONATED ACCELERATED RADIOTHERAPY IN SPLIT COURSE FOR STAGE IIIA AND STAGE IIIB NONSMALL CELL LUNG-CANCER - RESULTS OF A PHASE I-II STUDY BY THE GOTHA GROUP

The prognosis of stage III non-small cell lung cancer (NSCLC) can be i mproved by a combination of radiotherapy (PT) and chemotherapy (CT). I n this study, the GOTHA group evaluated the feasibility, tolerance, tu mour response, pattern of failure and effect on survival of a combinat ion alternating accelerated hyperfractionated (AH) PT and CT in patien ts with tumour stage III NSCLC. 65 patients received 3 cycles of cispl atin 60 mg/m(2) and mitomycin C 8 mg/m(2) on day 1, and vindesin 3 mg/ m(2) on days 1 and 8 in weeks 1-2, 5-6 and 9-10, alternating with AHRT , 2 daily 1.5 Gy fractions, 5 days/week, in weeks 2-3 (30 Gy) and week s 6-7 (33 Gy). The dose actually delivered was >98% for RT, and 85-100 % for CT. Mean duration before last CT cycle was 9.5 weeks. Toxic effe cts were leucopenia, nausea and vomiting, mucositis, diarrhoea, alopec ia and peripheral neuropathy. 1 patient died of bronchial haemorrhage at the end of RT. 1 of 5 patients, who underwent secondary pulmonary r esections, died of acute respiratory distress syndrome. Evaluation of tumour response was hampered by lung condensations in radiation fields . Some long-term survivors had an initial tumour response assessed as partial response or no change. First failures were more frequent outsi de (34) than within (21) radiation fields. The median survival was 15. 7 months and the 5 year survival rate was 15% (95% CI = 6-26%). 1 pati ent died of bladder cancer and another of myocardial infarction. Alter nating CT and AHRT, as used in this study, were well tolerated and all owed full dose delivery within less than 12 weeks. Initial response wa s not predictive of survival. The survival curve is encouraging and th e 5 year survival is superior to the 5% generally observed with conven tionally fractionated radiotherapy.