Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis.

Andrea Ardizzoni, Luca Boni, Marcello Tiseo, Frank V. Fossella, Joan H. Schiller, Marianne Paesmans, Davorin Radosavljevic, Adriano Paccagnella, Petr Zatloukal, Paola Mazzanti, Donald Bisset, Rafael Rosell

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Abstract

BACKGROUND: Because the efficacy of carboplatin and cisplatin in the treatment of advanced non-small-cell lung cancer (NSCLC) has not been proven to be equivalent, an individual patient data meta-analysis comparing the two treatments was performed. METHODS: Randomized trials comparing carboplatin to cisplatin in first-line treatment of advanced NSCLC were identified and their electronic databases obtained. A general variance-based method was used to estimate the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) for mortality, objective response, and toxicity. Cochran's chi-square test (Q test) was used to test for heterogeneity among trials, and the I2 index, which expresses the proportion of variability of the results due to heterogeneity, was calculated. A random-effects model that takes into account interstudy variation was also applied. All statistical tests were two-sided. RESULTS: Nine trials that included a total of 2968 patients were analyzed; overall median follow-up was 1021 days. The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; OR = 1.37; 95% CI = 1.16 to 1.61; P<.001). Carboplatin treatment was associated with a non-statistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95% CI = 0.99 to 1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95% CI = 1.01 to 1.23 and HR = 1.11; 95% CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopenia was more frequent during carboplatin-based chemotherapy. CONCLUSIONS: Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.

Original languageEnglish (US)
Pages (from-to)847-857
Number of pages11
JournalJournal of the National Cancer Institute
Volume99
Issue number11
DOIs
StatePublished - Jun 6 2007

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Carboplatin
Non-Small Cell Lung Carcinoma
Cisplatin
Meta-Analysis
Drug Therapy
Confidence Intervals
Therapeutics
Mortality
Odds Ratio
Poisons
Chi-Square Distribution
Thrombocytopenia
Nausea
Vomiting
Databases
Survival
Neoplasms

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer : an individual patient data meta-analysis. / Ardizzoni, Andrea; Boni, Luca; Tiseo, Marcello; Fossella, Frank V.; Schiller, Joan H.; Paesmans, Marianne; Radosavljevic, Davorin; Paccagnella, Adriano; Zatloukal, Petr; Mazzanti, Paola; Bisset, Donald; Rosell, Rafael.

In: Journal of the National Cancer Institute, Vol. 99, No. 11, 06.06.2007, p. 847-857.

Research output: Contribution to journalArticle

Ardizzoni, A, Boni, L, Tiseo, M, Fossella, FV, Schiller, JH, Paesmans, M, Radosavljevic, D, Paccagnella, A, Zatloukal, P, Mazzanti, P, Bisset, D & Rosell, R 2007, 'Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis.', Journal of the National Cancer Institute, vol. 99, no. 11, pp. 847-857. https://doi.org/10.1093/jnci/djk196
Ardizzoni, Andrea ; Boni, Luca ; Tiseo, Marcello ; Fossella, Frank V. ; Schiller, Joan H. ; Paesmans, Marianne ; Radosavljevic, Davorin ; Paccagnella, Adriano ; Zatloukal, Petr ; Mazzanti, Paola ; Bisset, Donald ; Rosell, Rafael. / Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer : an individual patient data meta-analysis. In: Journal of the National Cancer Institute. 2007 ; Vol. 99, No. 11. pp. 847-857.
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abstract = "BACKGROUND: Because the efficacy of carboplatin and cisplatin in the treatment of advanced non-small-cell lung cancer (NSCLC) has not been proven to be equivalent, an individual patient data meta-analysis comparing the two treatments was performed. METHODS: Randomized trials comparing carboplatin to cisplatin in first-line treatment of advanced NSCLC were identified and their electronic databases obtained. A general variance-based method was used to estimate the summary hazard ratios (HRs), odds ratios (ORs), and their 95{\%} confidence intervals (CIs) for mortality, objective response, and toxicity. Cochran's chi-square test (Q test) was used to test for heterogeneity among trials, and the I2 index, which expresses the proportion of variability of the results due to heterogeneity, was calculated. A random-effects model that takes into account interstudy variation was also applied. All statistical tests were two-sided. RESULTS: Nine trials that included a total of 2968 patients were analyzed; overall median follow-up was 1021 days. The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30{\%} versus 24{\%}, respectively; OR = 1.37; 95{\%} CI = 1.16 to 1.61; P<.001). Carboplatin treatment was associated with a non-statistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95{\%} CI = 0.99 to 1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95{\%} CI = 1.01 to 1.23 and HR = 1.11; 95{\%} CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopenia was more frequent during carboplatin-based chemotherapy. CONCLUSIONS: Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.",
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T1 - Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer

T2 - an individual patient data meta-analysis.

AU - Ardizzoni, Andrea

AU - Boni, Luca

AU - Tiseo, Marcello

AU - Fossella, Frank V.

AU - Schiller, Joan H.

AU - Paesmans, Marianne

AU - Radosavljevic, Davorin

AU - Paccagnella, Adriano

AU - Zatloukal, Petr

AU - Mazzanti, Paola

AU - Bisset, Donald

AU - Rosell, Rafael

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N2 - BACKGROUND: Because the efficacy of carboplatin and cisplatin in the treatment of advanced non-small-cell lung cancer (NSCLC) has not been proven to be equivalent, an individual patient data meta-analysis comparing the two treatments was performed. METHODS: Randomized trials comparing carboplatin to cisplatin in first-line treatment of advanced NSCLC were identified and their electronic databases obtained. A general variance-based method was used to estimate the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) for mortality, objective response, and toxicity. Cochran's chi-square test (Q test) was used to test for heterogeneity among trials, and the I2 index, which expresses the proportion of variability of the results due to heterogeneity, was calculated. A random-effects model that takes into account interstudy variation was also applied. All statistical tests were two-sided. RESULTS: Nine trials that included a total of 2968 patients were analyzed; overall median follow-up was 1021 days. The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; OR = 1.37; 95% CI = 1.16 to 1.61; P<.001). Carboplatin treatment was associated with a non-statistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95% CI = 0.99 to 1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95% CI = 1.01 to 1.23 and HR = 1.11; 95% CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopenia was more frequent during carboplatin-based chemotherapy. CONCLUSIONS: Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.

AB - BACKGROUND: Because the efficacy of carboplatin and cisplatin in the treatment of advanced non-small-cell lung cancer (NSCLC) has not been proven to be equivalent, an individual patient data meta-analysis comparing the two treatments was performed. METHODS: Randomized trials comparing carboplatin to cisplatin in first-line treatment of advanced NSCLC were identified and their electronic databases obtained. A general variance-based method was used to estimate the summary hazard ratios (HRs), odds ratios (ORs), and their 95% confidence intervals (CIs) for mortality, objective response, and toxicity. Cochran's chi-square test (Q test) was used to test for heterogeneity among trials, and the I2 index, which expresses the proportion of variability of the results due to heterogeneity, was calculated. A random-effects model that takes into account interstudy variation was also applied. All statistical tests were two-sided. RESULTS: Nine trials that included a total of 2968 patients were analyzed; overall median follow-up was 1021 days. The objective response rate was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; OR = 1.37; 95% CI = 1.16 to 1.61; P<.001). Carboplatin treatment was associated with a non-statistically significant increase in the hazard of mortality relative to treatment with cisplatin (HR = 1.07; 95% CI = 0.99 to 1.15; P = .100). In patients with nonsquamous tumors and those treated with third-generation chemotherapy, carboplatin-based chemotherapy was associated with a statistically significant increase in mortality (HR = 1.12; 95% CI = 1.01 to 1.23 and HR = 1.11; 95% CI = 1.01 to 1.21, respectively). Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopenia was more frequent during carboplatin-based chemotherapy. CONCLUSIONS: Our individual patient data meta-analysis suggests that cisplatin-based chemotherapy is slightly superior to carboplatin-based chemotherapy in terms of response rate and, in certain subgroups, in prolonging survival without being associated with an increase in severe toxic effects. Therefore, cisplatin-based third-generation regimens should remain the standard reference for the treatment of selected patients with advanced-stage NSCLC and of those with earlier-stage disease.

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