Randomised trial of four-drug vs less intensive two-drug chemotherapy in the palliative treatment of patients with small-cell lung cancer (SCLC) and poor prognosis. Medical Research Council Lung Cancer Working Party.

This randomised trial was conducted to compare a four-drug chemotherapy regimen as a control vs a less intensive two-drug regimen in terms of quality of life (QL), tumour response and survival in the palliative treatment of patients with small-cell lung cancer (SCLC) and poor prognosis. A total of 310 patients with extensive SCLC or limited disease but poor performance status were allocated at random to two chemotherapy regimens, each given on 3 consecutive days at 3 week intervals for three cycles: etoposide, cyclophosphamide, methotrexate and vincristine (ECMV, 154 patients) or etoposide and vincristine (EV, 156 patients). QL was assessed by patients using the Rotterdam Symptom Checklist, the Hospital Anxiety and Depression Scale and a daily diary card. Specific disease- and treatment-related symptoms were recorded by clinicians. The levels of palliation were high and similar in the two groups, although the ECMV regimen was on balance superior in palliating physical symptoms and reducing psychological distress. The EV regimen caused less toxicity, particularly mucositis, which, using Kaplan-Meier curves, occurred in an estimated 34% of patients compared with 54% in the ECMV group. The estimated rates of WHO grade 2 or worse haematological toxicity were 21% in the EV compared with 38% in the ECMV patients. There was no overall difference in response or survival; the median survival periods were 141 days in the ECMV group and 137 in the EV group and the survival rates 37% and 38% at 6 months and 12% and 10% at 1 year respectively. Nevertheless, 37 ECMV patients died within 3 weeks of starting the first cycle of chemotherapy (24 of them during the 2nd week) compared with 18 (9) EV patients. The EV regimen is a useful palliative regimen for patients with SCLC and poor prognosis.