Background: Single-drug oral etoposide daily for 5 days or more in 3-week cycles is commonly used as palliative chemotherapy for small-cell lung cancer (SCLC). However, there have been no randomised trials to compare this treatment with standard intravenous multidrug chemotherapy. Our objective was such a comparison in patients with poor performance status. However, before the planned intake of 450 patients had been completed the trial was stopped on the recommendation of an independent data monitoring committee, because of the inferiority of oral etoposide. We report the interim findings of the trial.
Methods: Patients of either sex and any age were entered into the trial if they had: previously untreated, microscopically confirmed SCLC; WHO grade performance status 2-4; no contraindications to either treatment regimen; normal renal function; and plasma bilirubin concentrations of less than 35 mumol/L. Patients with grade 4 performance status were likely to benefit from chemotherapy. Between September, 1992, and August, 1995, 339 patients were randomly allocated four cycles of 50 mg oral etoposide twice daily for 10 days (171 patients) or a standard intravenous regimen of etoposide and vincristine (EV), or cyclophosphamide, doxorubicin, and vincristine (CAV, 168 controls). The intake was stopped in September, 1995. Patients were assessed by clinicians before the start of treatment, at each attendance for treatment, at 3 months after randomisation, every month to 6 months, every 2 months to 1 year, then every 3 months thereafter. The primary endpoint was the palliation of major symptoms at 3 months after randomisation-ie, a reduction in cough, pain, anorexia, and shortness of breath scores. Secondary endpoints were quality of life, clinical and radiographic tumour response, and survival.
Findings: The palliative effects of treatment were similar in the etoposide group and control group (41% vs 46%). Grade 2 or worse haematological toxicity occurred in 35 (29%) etoposide-treated patients and 26 (21%) controls. Controls had a higher overall response rate than etoposide-treated patients (51% vs 45%). There was a small disadvantage in survival associated with oral etoposide (hazard ratio 1.35 [95% CI 1.03-1.79], p = 0.03). Median survival was 130 days in the etoposide group and 183 days in the controls; survival rates were 35% and 49% at 6 months and 11% and 13% at 12 months, respectively.
Interpretation: Oral etoposide 50 mg twice daily for 10 days every 3 weeks for four cycles is inferior to standard intravenous multidrug chemotherapy in the palliative treatment of patients with SCLC and poor performance status. Oral etoposide alone should no longer be used in the treatment of such patients.