Etoposide combined with cyclophosphamide plus vincristine compared with doxorubicin plus cyclophosphamide plus vincristine and with high-dose cyclophosphamide plus vincristine in the treatment of small-cell carcinoma of the lung: a randomized trial of the Bristol Lung Cancer Study Group.

Abstract

A total of 353 patients with previously untreated small-cell lung cancer (SCLC) were accrued in this multicenter trial. Patients were randomly assigned to receive one of the following three regimens: cyclophosphamide 1,000 mg/m2 intravenously (IV) day 1, vincristine 1.4 mg/m2 IV day 1, and etoposide 50 mg/m2 IV day 1, followed by etoposide 100 mg/m2/day orally days 2 through 5 (CEV); cyclophosphamide 1,000 mg/m2 IV day 1, vincristine 1.4 mg/m2 IV day 1, and doxorubicin 50 mg/m2 IV day 1 (CAV); cyclophosphamide 2,000 mg/m2 day 1 and vincristine 1.4 mg/m2 IV day 1 (CV). Cycles were repeated every 3 weeks. Treatment groups were comparable with respect to extent of disease, age, sex, performance status, and metastatic sites. No significant differences in response rates, response duration, or survival could be detected in limited disease, although there appeared to be a trend favoring CEV. Among extensive-disease patients, response duration on the CEV regimen was longer than on the CV regimen or the CAV program (P less than .001). The superiority of the CEV regimen was also demonstrated in the survival analysis in which differences attained statistical significance (P = .01). In this group the median survival was increased from 29 weeks on CV to 31 weeks on CAV and 39 weeks on CEV. Myelosuppression was the most frequent toxicity. It was more severe with CV than CEV or CAV. Most nonhematologic side effects were comparable among the three treatment groups. However, the high doses of cyclophosphamide in the CV regimen produced a higher incidence of hemorrhagic cystitis than in the CEV or CAV programs (P less than .001). Cardiotoxicity only occurred in the CAV group (P = .05). The addition of etoposide to the CV regimen resulted in significantly longer response duration and survival without increased toxicity. Similarly, the substitution of etoposide for the doxorubicin in the CAV regimen was associated with prolonged survival and reduced cardiotoxicity.

Small Cell Lung Cancer: Analysis of Factors Influencing the Response to Treatment and Survival

“…The results of the present study confirm the findings in the literature that patients with LD who attain a complete response to treatment have a significantly superior RD, TTF and survival [9,[42][43][44][45][46], The median survival of ambulatory patients (PS 0-1) with LD in the present study was significantly better than those of patients with a poor PS (PS 2-4). When RD and TTF were considered, a good PS significantly contributed to a favourable progno sis, while a poor PS was indicative of a poor prognosis.…”

Practice guideline for the role of combination chemotherapy in the initial management of limited-stage small-cell lung cancer

“…With one exception [13], none of the combination regimens tested against either CAV or EP has been shown to improve survival in these patients [7][8][9][10][11][12][14][15][16][17][18]. Additional randomized trials of combination chemotherapy regimens, neither of which was EP or CAV, detected no significant survival differences between the treatment arms [19][20][21][22][23].…”

“…Three trials detected no differences in survival [11,12,14], while one trial [13] detected a statistically significant survival advantage for the regimen of cyclophosphamide, etoposide, vincristine, and methotrexate (12 months versus 9 months, P = 0.0097). However, this trial was small (60 patients with limited disease) and used sequential delivery of thoracic radiation.…”

“…CAV was compared to non-platinum, etoposidecontaining regimens in four trials in which thoracic radiation was delivered sequentially [12][13][14] or not at all [11]. Three trials detected no differences in survival [11,12,14], while one trial [13] detected a statistically significant survival advantage for the regimen of cyclophosphamide, etoposide, vincristine, and methotrexate (12 months versus 9 months, P = 0.0097).…”

“…Details of randomized studies of these strategies are summarized in Table 4. One trial, previously reported in this guideline, included a dose-intensified treatment arm [12]; however, the comparison treatments included a third agent and were not directly comparable to the two-agent intensified regimen. Results of studies of dose-intensive chemotherapy regimens have been conflicting.…”