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

Abstract

The intensification of platinum dose (cisplatin plus carboplatin) in combination chemotherapy significantly increased the complete response rate, overall survival and number of two-year survivors among SCLC patients with limited disease compared to combination therapy with carboplatin alone, suggesting that a more aggressive treatment to this category of patients is worthwhile, while no difference in treatment outcome was observed for patients with extensive disease.

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

“…One of the trials detected a survival benefit for the intensified regimen in the subgroup of 143 patients with limited disease (median, 13.7 months versus 10.8 months, P = 0.039 log rank) [49], although radiotherapy was not routinely given in this trial. There was no statistical difference in survival between treatments in the other trial [48].…”

“…There were 21 randomized trials, three published in abstract form, which compared at least two chemotherapy regimens for SCLC ; seven randomized trials involving at least one alternating chemotherapy regimen (i.e., trials in which two different chemotherapy combinations were delivered in an alternating sequence) [22,24,[28][29][30][31][32]; four randomized trials which compared schedules or routes of administration of etoposide or formulations of etoposide [33][34][35][36]; 14 trials comparing a standard regimen to a dose-intensive one [37][38][39][40][41][42][43][44][45][46][47][48][49][50]; and six trials of duration of chemotherapy [51][52][53][54][55][56]. Note that two trials [22,24] appear in two sets of comparisons.…”

“…Several strategies to increase the dose intensity of chemotherapy have been examined, including: (a) increasing the dose of individual components of a regimen [37][38][39][40]; (b) accelerating delivery by decreasing the interval between cycles of chemotherapy [41][42][43][44]; (c) both increasing drug doses and decreasing the interval between cycles [45]; (d) using multiple active agents to form weekly, multi-drug regimens [46,47] or adding drugs to a standard-intensity regimen [48,49]; and (e) intensification through autologous bone marrow transplantation [50]. Details of randomized studies of these strategies are summarized in Table 4.…”

“…Urban et al [48] and Hirsch et al [49] compared a control regimen of cyclophosphamidedoxorubicin-etoposide and carboplatin-teniposide-vincristine-cyclophosphamide-epirubicin, respectively, with one in which intensification was achieved through the addition of cisplatin. One of the trials detected a survival benefit for the intensified regimen in the subgroup of 143 patients with limited disease (median, 13.7 months versus 10.8 months, P = 0.039 log rank) [49], although radiotherapy was not routinely given in this trial.…”

First-line chemotherapy in metastatic small-cell lung cancer (SCLC)

“…This higher toxicity may have contributed to the advantage of the carboplatin protocol. Similar activity of both platinum analogues can be assumed also from the results of the study by Hirsch et al [12]. In this investigation 280 patients were randomized to receive either carboplatin/AUC 4 day 1, cisplatin 35 mg/m 2 days 2 and 3, teniposide 50 mg/m 2 days 1-5 and vincristine 1.3 mg/m 2 day 1 every 4 weeks or the same regimen without cisplatin.…”