SMALL-CELL LUNG-CANCER (SCLC) - A RANDOMIZED TRIAL OF CYCLOPHOSPHAMIDE, ADRIAMYCIN, VINCRISTINE PLUS ETOPOSIDE (CAV-E) OR TENIPOSIDE (CAV-T) AS INDUCTION TREATMENT, FOLLOWED IN COMPLETE RESPONDERS BY ALPHA-INTERFERON OR NO TREATMENT, AS MAINTENANCE THERAPY

In this phase III, double-random study, we compared CAV-E to CAV-T com bination as induction treatment (Ist randomization) for SCLC. Subseque ntly, patients achieving a complete response (CR) were randomized agai n (2nd randomization) to receive maintenance treatment with alpha-IFN or no treatment. From June 1990 to June 1992, 75 untreated patients we re enrolled in this trial. After stratification according to limited d isease (LD) or extensive disease (ED), patients were randomized to rec eive the following treatment: cyclophosphamide 1000 mg/m(2), adriamyci n 50 mg/m(2), vincristine 2 mg, day 1 i.v., plus etoposide (E) 100 mg/ m(2) (CAV-E: arm-A) or teniposide (T) 60 mg/m(2) on day 2, 3, 4 i.v., every 3 weeks (CAV-T: arm-B). LD patients after 3 cycles of treatment received chest radiotherapy and 2 further cycles, whereas ED patients received 5 consecutive cycles. Patients who achieved a CR entered the 2nd randomization receiving alpha-IFN (3x10(6) I.U., i.m. daily x 9 mo nths) or no treatment. A second-line treatment with carboplatin 300 mg /m(2) plus E (if T was initially used) or T (if E was initially used) was also scheduled for patients achieving less than CR to induction tr eatment. Preliminary results are as follows: 75 patients were randomiz ed, 72 were eligible for survival (arm-A = 37 and arm-B = 35) and 60 w ere fully evaluable for response (arm-A = 34 and arm-B = 26). In patie nts with LD the overall response rate was 79% (CR 21%) in arm-A vs 92% (CR 50%) in arm-B. In patients with ED, the overall response rate was 80% (CR 33%) in arm-A vs 84% (CR 7%) in arm-B. At a mean observation time of about 1 year (range 1-25 months), median survival of LD patien ts was 15 months in arm-A and 13 months in arm-B (Chi-square = 1.55; p >0.05); in ED patients survival was 10.8 months and 8 months respectiv ely (Chi-square = 2.88; p>0.05). Cumulative survival probability was i dentical (12 months) in all patients of both arms. Toxicity was mainly haematologic and gastrointestinal: WHO grade 3-4 myelosuppression and vomiting were observed in 20% and 11% respectively, of cycles deliver ed in arm-A, compared to 19% and 8%, respectively, of cycles in arm-B. Two septic deaths occurred with CAV-T, while 1 patient discontinued t reatment due to persistent myelosuppression with CAV-E. After the firs t and second-line treatment 20 patients showed a CR. Five of them refu sed further treatment, while 15 accepted to enter the 2nd randomizatio n. At the time of analysis, 9 patients were allocated to the alpha-IFN arm and 6 to the control arm. Although the study is still running, th e 2nd randomization accrual appears inadequate to achieve the second o bjective within a reasonable time.