COMPARISON OF ORAL ETOPOSIDE AND STANDARD INTRAVENOUS MULTIDRUG CHEMOTHERAPY FOR SMALL-CELL LUNG-CANCER - A STOPPED MULTICENTER RANDOMIZED TRIAL

Background Single-drug oral etoposide daily for 5 days or more in 3 we ek cycles is commonly used as palliative chemotherapy for small-cell l ung cancer (SCLC). However, there have been no randomised trials to co mpare 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 c ompleted the trial was stopped on the recommendation of an independent data monitoring committee, because of the inferiority of oral etoposi de. We report the interim findings of the trial. Methods Patients of e ither sex and any age were entered into the trial if they had: previou sly untreated, microscopically confirmed SCLC; WHO grade performance s tatus 2-4; no contraindications to either treatment regimen; normal re nal function; and plasma bilirubin concentrations of less than 35 mu m ol/L. Patients with grade 4 performance status were likely to benefit from chemotherapy. Between September, 1992, and August, 1995, 339 pati ents 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 treatm ent, at each attendance for treatment, at 3 months after randomisation , every month to 6 months, every 2 months to 1 year, then every 3 mont hs thereafter. The primary endpoint was the palliation of major sympto ms at 3 months after randomisation-ie, a reduction in cough, pain, ano rexia, and shortness of breath scores. Secondary endpoints were qualit y of life, clinical and radiographic tumour response, and survival. Fi ndings The palliative effects of treatment were similar in the etoposi de group and control group (41% vs 46%). Grade 2 or worse haematologic al toxicity occurred in 35 (29%) etoposide-treated patients and 26 (21 %) controls. Controls had a higher overall response rate than etoposid e-treated patients (51% vs 45%). There was a small disadvantage in sur vival 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 etopo side 50 mg twice daily for 10 days every 3 weeks for four cycles is in ferior to standard intravenous multidrug chemotherapy in the palliativ e treatment of patients with SCLC and poor performance status. Oral et oposide alone should no longer be used in the treatment of such patien ts.