Is carboplatin based chemotherapy as effective as cisplatin based chemotherapy for treatment of stage IV inoperable NSCLC?

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Introduction

The majority of patients treated with NSCLC have stage IV disease, with common sites of metastases including lymph nodes, the pleura, liver, adrenal glands, bone and brain. Consequently, systemic therapy has been the mainstay of treatment attempting to control overall disease. A historical summary of the evolution of systemic drug treatment for stage IV NSCLC can be found here. The focus of the following question is based on the evidence in support of the old and new practice paradigms for stage IV NSCLC. Empirical therapy refers to therapy given to all fit patients deemed suitable without any particular restrictions.

Carboplatin versus cisplatin

Three meta-analyses have addressed the question of whether carboplatin based chemotherapy is as effective as cisplatin based,[1][2][3] which collectively confirm that cisplatin based regimens are associated with a slightly higher response rate than carboplatin regimens, with no definite survival difference.The first meta-analysis by Hotta et al, evaluated 2948 patients from eight randomised controlled trials (RCTs) from 1990-2004.[1]. Cisplatin-based chemotherapy produced a higher response rate (RR), but overall survival (OS) was not significantly different.[1] The second, by Ardizzoni et al, was an individual patient data meta-analysis of 2968 patients from nine RCTs from 1990 to 2004. This study found that objective RR was higher for patients treated with cisplatin than for patients treated with carboplatin (30% versus 24%, respectively; Odds ratio (OR) = 1.37; 95% CI = 1.16 to 1.61; P <.001).[2] There was no overall difference in mortality, however, as in the Jiang meta-analysis, a subset analysis of survival in five trials evaluating “new” agents (gemcitabine, docetaxel, paclitaxel and vinorelbine) found OS with carboplatin slightly inferior to cisplatin (hazard ratio (HR) = 1.12; 95% CI = 1.01 to 1.23).[2] Cisplatin-based chemotherapy was associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopaenia was more frequent during carboplatin-based chemotherapy.[2] Jiang et al, evaluated published data from 6906 patients from 18 RCTs from 1990-2006.[3] This study confirmed the findings of Hotta and Arziddoni with regard to RR in favour of cisplatin, however it did not find any survival difference in eight studies evaluating the new agents above.[3]

A more recent Cochrane review of cisplatin versus carboplatin in combination with third-generation drugs found that no survival difference, slightly higher response rates to cisplatin in the overall analysis, but that trials using paclitaxel or gemcitabine had equivalent response rates for cisplatin or carboplatin. [4]

The question of whether to use cisplatin versus carboplatin is of lower significance today especially given the new information arguing in favour of selecting specific treatments for greater benefit by histology and the presence of activating gene mutations.


Evidence summary and recommendations

Evidence summary Level References
First-line chemotherapy involving cisplatin results in a slightly higher likelihood of tumour response than the same chemotherapy with carboplatin.

Last reviewed September 2017

I [1], [2], [3]
There is no definite overall survival difference between cisplatin or carboplatin based first-line chemotherapy.

Last reviewed September 2017

I [1], [2], [3]
Cisplatin-based chemotherapy is associated with more severe nausea and vomiting and nephrotoxicity; severe thrombocytopaenia is more frequent during carboplatin-based chemotherapy.

Last reviewed September 2017

I [1], [2], [3]
Evidence-based recommendationQuestion mark transparent.png Grade
In patients with high tumour burden and symptoms from stage IV NSCLC cisplatin based chemotherapy may be used in preference to carboplatin for the purpose of inducing a response, however, this benefit may be offset by its greater risk of toxicity.

Last reviewed September 2017

B


Practice pointQuestion mark transparent.png

The choice of cisplatin versus carboplatin in a given patient may consider the balance between perceived benefit (in tumour response) versus known toxicity, whilst considering patient preferences.
Last reviewed September 2017

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References

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Appendices

Further resources

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