Cisplatin versus carboplatin in combination with third-generation drugs for advanced non-small cell lung cancer.
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.


OBJECTIVE
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.


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.


METHODS
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.


METHODS
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.


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.


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.
Clinical Oncology, Instituto do Câncer do Estado de Sao Paulo (ICESP/FMUSP), Av. Doutor Arnaldo 251 - Cerquiera César, São Paulo, Brazil, 01246-000.
Tiago B
TB
de Castria
Edina M K
EM
da Silva
Aecio F T
AF
Gois
Rachel
R
Riera
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D000093542:Gemcitabine
D003841:Deoxycytidine; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine