Is there a case for cisplatin in the treatment of small-cell lung cancer? A meta-analysis of randomized trials of a cisplatin-containing regimen versus a regimen without this alkylating agent

Abstract

Summary Chemotherapy is the backbone of small-cell lung cancer therapy. However, optimal drug combinations and schedules remain to be defined and there is hitherto no world-wide accepted standard regimen. Cisplatin, an alkylating agent with high putative toxicity is currently widely used although its effectiveness in this disease has not been established firmly. We conducted a meta-analysis of published data reporting trials randomizing a cisplatin-containing regimen versus a regimen without this alkylating agent in order to determine possible differences in survival response and toxicity. Nineteen trials have been identified in medical literature (4054 evaluable patients). Ten trials randomized patients to receive a cisplatin-etoposide regimen versus a regimen without any of these two drugs. A subgroup analysis was, therefore, carried out in the nine remaining trials that randomly allocated patients between two regimens differing in the absence or presence of cisplatin, whereas etoposide was given (or not given) in both arms (1579 evaluable patients). The DerSimonian and Laird method was used to estimate the size effects and the Peto and Yusuf method was used in order to generate the odds ratios (OR) of reduction in risk of death and the increase in probability of being responders to chemotherapy. There was no significant difference between the cisplatin-containing regimen and the regimen without this drug when the risk of toxic-death was taken into account with respective probabilities of 3.1 and 2.7% (NS). Patients randomized in a cisplatin-containing regimen had an increase in probability of being responders with an OR of 1.35, 95% confidence interval (CI) of 1.18-1.55; P < 10 -5 corresponding to an increase of objective (partial plus complete) response rate from 0.62 to 0.69 (a result taking into account a significant heterogeneity). Patients treated with a cisplatin-containing regimen benefited from a significant reduction of risk of death at 6 months and 1 year with respective OR 0.87, 95% CI 0.75-0.98, P = 0.03, and or 0.80, 95% CI 0.69-0.93, P = 0.002 (no statistical heterogeneity). This corresponded to a significant increase in the probability of survival of 2.6% and 4.4% at 6 months and 1 year respectively. The meta-analysis restricted to the subset of nine trials without etoposide treatment imbalance reached similar conclusions. A cisplatin-containing regimen yields a higher response rate and probability of survival than does a chemotherapy containing others alkylating agents without a perceptible increase in risk of toxic-death. (2000) 83(1), 8-15 © 2000 Cancer Research Campaign doi: 10.1054/ bjoc.2000.1164, available online at http://www.idealibrary.com on *Present address: Cliniques Universitaires UCL de Mont-Godinne, B 5530 Yvoir, Belgium combination versus radiotherapy alone has demonstrated that the combined modality treatment reduces the risk of death. This effect is particularly apparent where the chemotherapy is based on a modern combination. It is noteworthy that the break between older ...

Genitourinary Small-Cell Carcinoma: A Single-Institution Experience

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Phase II study of irinotecan combined with carboplatin in previously untreated small-cell lung cancer

“…Recent large randomized trials of cisplatin/etoposide with or without newer cytotoxic agents have demonstrated a MST of 8.0 -10.6 months in previously untreated patients with ED-SCLC (De Marinis et al, 2003, Georgoulias et al, 2004Niell et al, 2005). In addition, a recent meta-analysis of randomized trials demonstrated that patients who received a regimen containing cisplatin had a significant increase in the probability of response and survival (Pujol et al, 2000;Hotta et al, 2004). Thus, we consider irinotecan/carboplatin of value as a convenient carboplatin-containing two-drugs regimen with similar activity to cisplatin-containing regimens, except irinotecan/cisplatin in patients with ED-SCLC.…”

Progress in the management and outcome of small-cell lung cancer in a French region from 1981 to 1994

“…As in other countries, the combination of cisplatin and etoposide with or without other drug(s) became the standard chemotherapy in our region. In a metaanalysis of randomized trials of cisplatin-containing regimens versus regimens without cisplatin, the former was associated with a significant increase of survival of 2.6% at 6 months and 4.4% at 1 year (Pujol et al, 2000a). Paesmans et al showed that the administration of cisplatin and etoposide as components of a polychemotherapy regimen, separately or together, improved survival of SCLC patients (Paesmans et al, 1999).…”