Feasibility of escalating daily doses of cisplatin in combination with accelerated radiotherapy in non-small cell lung cancer.

The aim of this study was to determine whether it is feasible to reduce the overall treatment time from 7 to 4 weeks in patients with non-small cell lung cancer (NSCLC) receiving radiotherapy with cisplatin. This follows an EORTC phase III randomised trial (08844) in which cisplatin given before each radiation dose resulted in improved local control and survival, but which had a relatively long treatment period of 7 weeks [Schaake-Koning et al., N Engl J Med 1992, 326, 524-530]. 38 patients with confirmed NSCLC (2 stage I, 1 stage II, 18 stage IIIA, 17 stage IIIB) received a total tumour dose of 55 Gy/20 fractions/26 days, from January 1992 to March 1994. Daily fractions of 2 Gy (5 times/week) were given to the macroscopic tumour and the non-involved adjacent lymph node areas. During the same session, a dose of 0.75 Gy was given to the macroscopic tumour (simultaneous boost). Cisplatin 6 mg/m2 was administered 1-2 h before each fraction, in an escalating total dose, during week 1 in 3 patients, during weeks 1 and 2 in 6 patients, during weeks 1, 2 and 3 in 5 patients and during the whole treatment in 24 patients. 38 patients were evaluable for acute side-effects (WHO). Maximal therapy-related toxicity (WHO) was grade 3 (nausea/vomiting in 2 patients, oesophagitis in 3 patients, dyspnoea in 3 patients, cough in 1 patient). Late side-effects were evaluated in 34 patients. There was grade 2 oesophagitis in 2 patients; grade 3 toxicity in 8 patients (tiredness in 3 patients, dyspnoea in 3 patients, oesophagitis in 2 patients); grade 4 toxicity in 4 patients (dyspnoea in 3 patients, cough in 1 patient). Pulmonary fibrosis grade 3 occurred in 4 and grade 4 in 6 patients. One patient developed a severe (grade 3) radiation pneumonitis. The low incidence of acute and late side-effects with this treatment, combining daily administration of 6 mg cisplatin with radical radiotherapy using a simultaneous boost technique, indicates that escalation of the radiation dose seems feasible.