A RANDOMIZED TRIAL OF LOW-DOSE HIGH-FREQUENCY CHEMOTHERAPY AS PALLIATIVE TREATMENT OF POOR-PROGNOSIS SMALL-CELL LUNG-CANCER - A CANCER-RESEARCH CAMPAIGN TRIAL/

We report the results of a randomised trial in extensive small-cell lu ng cancer (SCLC) of a novel approach to palliative chemotherapy. A wid ely used 3 weekly regimen was compared with the same drugs given at ha lf the dose but twice the frequency with the same intended overall dos e intensity (DI). A total of 167 patients defined as having extensive SCLC with adverse prognostic features were randomised to receive eithe r a 3 weekly regimen of cisplatin 60 mg m(-2) i.v. on day 1 and etopos ide 120 mg m(-2) i.v. on day 1 and 100 mg b.d. orally on days 2 and 3 alternating with cyclophosphamide 600 mg m(-2) i.v., doxorubicin 50 mg m(-2) i.v. and vincristine 2 mg i.v. ail on day 1 for a maximum of si x courses (3 weekly); or treatment with the same drugs but with each c ourse consisting of half the 3 weekly dose given every 10 or 11 days f or a maximum of 12 courses. In the 10/11 day regimen overall response rate was 58.9% (95% CI, 47.9-69.2%) with 12.8% complete responses (CR) . For the 3 weekly treatment the overall response rate was 44.9% (95% CI, 35.0-55.5%) with 10.1% CR. Median survival was similar in the two arms at 6.4 months (95% CI, 4.9-7.3 months) and 5.8 months (95% CI, 4. 0-6.6 months) respectively. Survival at 1 year was 9.9% (95% CI, 5.0-1 8.5%) and 8.9% (95% CI, 4.6-16.6%). The 95% CI for the difference in s urvival at 1 year is -7.09% to +9.09%. Haematological toxicity and tre atment delays owing to infection were more Frequent with the 10/11 day regimen but other toxicities were equal in both arms. Other aspects o f quality of life were measured in a small representative cohort of pa tients using a daily diary card (DDC). There was a trend of improved q uality of life on the 10/11 day arm, but there was little difference b etween the two treatments. The trial shows that a low-dose/high-freque ncy regimen with the same DI as conventionally scheduled chemotherapy gives similar response rates and survival. This and other modification s of the schedule may offer new approaches to palliative treatment of advanced cancer. However, in this trial there was no significant benef it in toxicity or other aspects of qualify of life.