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Article pour les cliniciens

La cisplatine par rapport à la carboplatine en combinaison avec des médicaments de troisième génération pour le cancer du poumon non à petites cellules avancé.



  • de Castria TB
  • da Silva EM
  • Gois AF
  • Riera R
Cochrane Database Syst Rev. 2013 Aug 16;(8):CD009256. doi: 10.1002/14651858.CD009256.pub2. (Review)
PMID: 23949842
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Disciplines
  • Oncology - Lung
    Relevance - 7/7
    Intérêt médiatique  - 6/7

Résumé (en anglais)

BACKGROUND: An estimated 220,000 new cases of non-small cell lung cancer (NSCLC) and 160,000 deaths are expected to occur in the US in 2013, representing about 28% of cancer-related mortality. Approximately 75% of these people will have locally advanced or metastatic disease and will be treated in a palliative setting. Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care.

OBJECTIVES: To assess the efficacy and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced NSCLC. To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug.

SEARCH METHODS: We searched the following electronic databases: MEDLINE (via PubMed) (1966 to 6 March 2013), EMBASE (via Ovid) (1974 to 6 March 2013), Cochrane Central Register of Controlled Trials (CENTRAL; Issue 2, 2013), and LILACS (1982 to 6 March 2013). In addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to March 2013), reference lists from relevant resources and the Clinical Trial.gov database.

SELECTION CRITERIA: Randomised clinical trials comparing regimens with carboplatin or cisplatin combined with a third-generation drug in people with locally advanced or metastatic NSCLC. We accepted any regimen and number of cycles that included these drugs, since there is no widely accepted standard regimen.

DATA COLLECTION AND ANALYSIS: Two review authors independently assessed search results and a third review author resolved any disagreements. We analysed the following endpoints: overall survival, one-year survival, quality of life, toxicity and response rate.

MAIN RESULTS: We included 10 trials with 5017 people, 3973 of whom were available for meta-analysis. There was no difference between carboplatin-based and cisplatin-based chemotherapy in overall survival (hazard ratio (HR) 1.00; 95% confidence interval (CI) 0.51 to 1.97, I(2) = 0%) and one-year survival rate (risk ratio (RR) 0.98; 95% CI 0.88 to 1.09, I(2) = 24%). Cisplatin had higher response rates when we performed an overall analysis (RR 0.88; 95% CI 0.79 to 0.99, I(2) = 3%), but trials using paclitaxel or gemcitabine plus a platin in both arms had equivalent response rates (paclitaxel: RR 0.89; 95% CI 0.74 to 1.07, I(2) = 0%; gemcitabine: RR 0.92; 95% CI 0.73 to 1.16, I(2) = 34%). Cisplatin caused more nausea or vomiting, or both (RR 0.46; 95% CI 0.32 to 0.67, I(2) = 53%) and carboplatin caused more thrombocytopenia (RR 2.00; 95% CI 1.37 to 2.91, I(2) = 21%) and neurotoxicity (RR 1.55; 95% CI 1.06 to 2.27, I(2) = 0%). There was no difference in the incidence of grade III/IV anaemia (RR 1.06; 95% CI 0.79 to 1.43, I(2) = 20%), neutropenia (RR 0.96; 95% CI 0.85 to 1.08, I(2) = 49%), alopecia (RR 1.11; 95% CI 0.73 to 1.68, I(2) = 0%) or renal toxicity (RR 0.52; 95% CI 0.19 to 1.45, I(2) = 3%). Two trials performed a quality of life analysis; however, they used different methods of measurement so we could not perform a meta-analysis.

AUTHORS' CONCLUSIONS: The initial treatment of people with advanced NSCLC is palliative, and carboplatin can be a treatment option. It has a similar effect on survival but a different toxicity profile when compared with cisplatin. Therefore, the choice of the platin compound should take into account the expected toxicity profile and the person's comorbidities. In addition, when used with either paclitaxel or gemcitabine, the drugs had an equivalent response rate.


Commentaires cliniques (en anglais)

Oncology - Lung

This meta-analysis provides support for the common US practice of using carboplatin-containing doublet rather than cisplatin in patients with advances NSCLC. The response rate (with paclitaxel or gemcitabine) and survival are the same. The toxicity profiles are similar with the expected notable differences in nausea/vomiting (cisplatin) and thrombocytopenia (carboplatin); unexpectedly, neurotoxicity was greater with carboplatin and nephrotoxicity was non-statistically greater with cisplatin.

Oncology - Lung

This is another log on the fire. This meta-analyses will not convince either side to change position, but reverses the prior "evidence": ...cisplatin was previously considered superior in response and survival, but more toxic; carbo easier to tolerate, more convenient. In other diseases, bladder, testis, H&N, the "Plat better" were more consistent. The recent RTOG study of high v low dose XRT used weekly Cb/Pctxl. It demonstrated surprising results, but not when one knows the data for Pctxl, a marketing triumph that has never fared well in comparison coupled with other drugs. I read the "concise version"...the issue of drug pairing, schedule, equivalent toxicity, and disease site will keep these fires with embers glowing, but the facts are that neither is good enough to rely on. No standard. We are in a muddle about radiotherapy methods as well as drug combinations, as the vast legion of forces are marching to molecular markers...choice of chemotherapeutics appears a boring subject.

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