Superiority of high-dose platinum (cisplatin and carboplatin) compared to carboplatin alone in combination chemotherapy for small-cell lung carcinoma: A prospective randomised trial of 280 consecutive patients

Purpose: A prospective randomized trial in small-cell lung cancer (SCLC) wa s performed to determine if intensification of the platinum dose by giving cisplatin and carboplatin in combination to patients with SCLC yields highe r response rates and survival, than carboplatin alone in a combination chem otherapy regimen. Patients and methods: Between September 1992 and October 1997, 280 patients were included in a two armed prospective randomized trial, stratified by s tage of disease, LDH and performance status. The treatment was in arm A: th ree courses induction chemotherapy with carboplatin (AUC = 4, day 1), cispl atin (35 mg/m(2), days 2 and 3), teniposide (50 mg/m(2), day 1-5), vincrist ine (1.3 mg/m(2), day 1) every four weeks, followed by cyclophosphamide (3 g/m(2), day 84), 4-epirubicin (4-epidoxorubicin) (150 mg/m(2), day 112), an d finally one course cisplatin, carboplatin, teniposide and vincristine, (d ays 140-144). Arm B also comprised a total of six courses, identical to tho se in arm A except for omission of cisplatin. Results: There were no significant differences in the overall treatment out come for A vs. B, in terms of response rates (72% in both arms), complete r esponse rates (40% and 34%, respectively), or median survival (314 days and 294 days, respectively). However, for patients with limited disease both t he CR rate (54% vs. 37%, P < 0.05), overall survival (log-rank test, P < 0. 05), and the two-year survival rate (11% vs. 6%, P < 0.05) were higher in t he high-dose platinum arm compared to the carboplatin alone arm. Conclusions: The intensification of platinum dose (cisplatin plus carboplat in) in combination chemotherapy significantly increased the complete respon se rate, overall survival and number of two-year survivors among SCLC patie nts with limited disease compared to combination therapy with carboplatin a lone, suggesting that a more aggressive treatment to this category of patie nts is worthwhile, while no difference in treatment outcome was observed fo r patients with extensive disease.