Comparing carboplatin-based chemotherapy with cisplatin-based chemotherapy in the treatment of people with advanced lung cancer

Review question

Is carboplatin more effective and less toxic than cisplatin in the treatment of people with advanced non-small cell lung cancer?

Background

Lung cancer is the leading cause of cancer death, and more than a half of people found to have the cancer have incurable disease at diagnosis. Non-small cell is the most common type of lung cancer, corresponding to approximately 85% of all lung cancer cases. Despite recent advances in targeted therapies and immunotherapy, platinum-based chemotherapy remains a useful and accessible option with well-established survival benefits for people with advanced non-small cell lung cancer. Although treatment regimens including cisplatin or carboplatin plus another agent are widely used, they can be associated with undesirable side effects. The aim of this systematic review was to determine which of these two frequently used drugs was more effective and caused fewer side effects.

Study characteristics

We found 11 trials (including 4046 people) that compared cisplatin with carboplatin, both combined with another modern drug, called a third-generation drug.

Key results

The drugs were equally effective at prolonging survival, but the toxicity profile was different. Carboplatin caused a greater decrease in the number of platelets (which control clotting) in the blood.

Quality of evidence

In this Cochrane review, we found that the quality of evidence was high for overall survival, one-year survival rate and response rate but moderate quality evidence for the other outcomes measured.

Authors' conclusions: 

Advanced NSCL patients treated with carboplatin or cisplatin doublet with third-generation chemotherapy drugs showed equivalent overall survival, one-year survival, and response rate. Regarding adverse events, carboplatin caused more thrombocytopenia, and cisplatin caused more nausea/vomiting. Therefore, in this palliative therapeutic intent, the choice of the platin compound should take into account the expected toxicity profile, patient's comorbidities and preferences.

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Background: 

Lung cancer is the most commonly diagnosed cancer and the leading cause of cancer death in both sexes worldwide. Approximately 50% of those diagnosed with lung cancer 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 effectiveness and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy, both in combination with a third-generation drug, in people with advanced non-small cell lung cancer (NSCLC). To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug.

Search strategy: 

We searched the following electronic databases: the Cochrane Central Register of Controlled Trials (CENTRAL; 13 January 2019), MEDLINE (via PubMed) (1966 to 13 January 2019), and Embase (via Ovid) (1974 to 13 January 2019). In addition, we handsearched the proceedings of the American Society of Clinical Oncology Meetings (January 1990 to September 2018) and reference lists from relevant resources.

Selection criteria: 

Randomised clinical trials (RCTs) 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 the search results, and a third review author resolved any disagreements. The primary outcomes were overall survival and health-related quality of life. The secondary outcomes were one-year survival rate, objective response rate and toxicity.

Main results: 

In this updated review, we located one additional RCT, for a total of 11 included RCTs (5088 participants, 4046 of whom were available for meta-analysis). There was no difference in overall survival (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.82 to 1.20; 10 RCTs; 2515 participants; high-quality evidence); one-year survival rate (risk ratio (RR) 0.98, 95% CI 0.89 to 1.08; I2 = 17%; 4004 participants; all 11 RCTs; high-quality evidence); or response rate (RR 0.89, 95% CI 0.79 to 1.00; I2 = 12%; all 11 RCTs; 4020 participants; high-quality evidence). A subgroup analysis comparing carboplatin with different doses of cisplatin found an overall survival benefit in favour of carboplatin-based regimens when compared to cisplatin at lower doses (40 to 80 mg/m2) (HR 1.15, 95% CI 1.03 to 1.28; 6 RCTs; 2508 participants), although there was no overall survival benefit when carboplatin-based chemotherapy was compared to cisplatin at higher doses (80 to 100 mg/m2) (HR 0.93, 95% CI 0.83 to 1.04; I2 = 0%; 4 RCTs; 1823 participants). Carboplatin caused more thrombocytopenia (RR 2.46, 95% CI 1.49 to 4.04; I2 = 68%; 10 RCTs; 3670 participants) and was associated with more neurotoxicity (RR 1.42, 95% CI 0.91 to 2.23; I2 = 0%, 5 RCTs; 1489 participants), although we believe this last finding is probably related to a confounding factor (higher dose of paclitaxel in the carboplatin-containing treatment arm of a large study included in the analysis). There was no statistically significant difference in renal toxicity (RR 0.52, 95% CI 0.19 to 1.45; I2 = 3%; 3 RCTs; 1272 participants); alopecia (RR 1.11, 95% CI 0.73 to 1.68; I2 = 0%; 2 RCTs; 300 participants); anaemia (RR 1.37, 95% CI 0.79 to 2.38; I2 = 77%; 10 RCTs; 3857 participants); and neutropenia (RR 1.18, 95% CI 0.85 to 1.63; I2 = 94%; 10 RCTs; 3857 participants) between cisplatin-based chemotherapy and carboplatin-based chemotherapy regimens. Two RCTs performed a health-related quality of life analysis; however, as they used different methods of measurement we were unable to perform a meta-analysis. One RCT reported comparative health-related quality of life data between cisplatin and carboplatin-containing arms but found no significant differences in global indices of quality of life, including global health status or functional scales.

In this Cochrane review, we found that the quality of evidence was high for overall survival, one-year survival rate and response rate but moderate quality evidence for the other outcomes measured.

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