Are non-platinum doublet chemotherapy regimens as effective as platinum doublet regimens for treatment of stage IV inoperable NSCLC?

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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.

Doublet chemotherapy regimens versus platinum doublet regimens

D’Addario et alevaluated this question in a meta-analysis of 7633 patients from 37 RCTs between 1983 and 2002.[1] Platinum-based therapy was associated with a 62% increase in the odds ratio (OR) for response rate (RR) (OR, 1.62; 95% CI,1.46 =1.8; P <.0001). The one-year overall survival (OS) was increased by 5% with platinum-based regimens (34% versus 29%; OR, 1.21; 95% CI, 1.09 to 1.35; P =.0003).[1] However, no statistically significant increase in one-year survival was found when platinum therapies were compared to 3G –based combination regimens (OR, 1.11; 95% CI, 0.96 to 1.28; P = .17).[1] The toxicity of platinum-based regimens was significantly higher for hematologic toxicity,nephrotoxicity, and nausea and vomiting, but not for neurotoxicity, febrile neutropaenia rate,or toxic death rate.[1]

Rajeswaran et al also evaluated this question in a meta-analysis of 4920 patients from 17 RCTs.[2] Platinum based doublet regimens were associated with a slightly higher one-year survival (RR = 1.08, 95% CI 1.01—1.16, p = 0.03), a greater response rate (RR = 1.11, 95% CI 1.02—1.21, p = 0.02), but with a higher risk of anaemia, nausea, and neurotoxicity.[2] Cisplatin-based doublet regimens improved one-year survival (RR = 1.16, 95% CI 1.06-1.27, p = 0.001), complete response. (RR = 2.29, 95% CI 1.08-4.88, p = 0.03), and partial response (RR = 1.19, 95% CI 1.07-1.32, p = 0.002), but with an increased risk of anaemia, neutropaenia, neurotoxicity and nausea.[2] Conversely, carboplatin based doublet regimens did not increase one-year survival (RR = 0.95, 95% CI 0.85—1.07,p = 0.43). However, although carboplatin-based doublet regimens were associated with higher risk of anaemia and thrombocytopaenia, there was no increased nausea and/or vomiting.[2]

Li et al compared the activity, efficacy, and toxicity of gemcitabine plus paclitaxel versus carboplatin plus either gemcitabine or paclitaxel in 2186 patients with untreated advanced NSCLC from four RCTSs.[3] A significant difference in RR favouring gemcitabine plus paclitaxel over carboplatin-based doublets was observed [OR = 1.20; 95% CI 1.02–1.42; P = 0.03], whereas the trend toward an improved one-year OS was not significant (OR = 1.07; 95% CI = 0.91–1.26; P = 0.41).[3] An increased risk of grade 3/4 toxicities for patients receiving carboplatin-based chemotherapy was demonstrated.[3]

Evidence summary and recommendations

Evidence summary Level References
Platinum-based doublet 3G chemotherapy is associated with a higher response rate and slightly higher one-year survival than non-platinum doublet chemotherapy.

Last reviewed September 2017

I [1], [2], [3]
Platinum-based doublet 3G chemotherapy is associated with greater risk of anaemia and thrombocytopaenia than non-platinum combination therapy.

Last reviewed September 2017

I [1], [2], [3]
Gemcitabine and paclitaxel improves response ratio without added toxicity, compared with gemcitabine or paclitexel and carboplatin combinations.

Last reviewed September 2017

I [3]
Evidence-based recommendationQuestion mark transparent.png Grade
Non-platinum 3G doublet chemotherapy is an effective alternative option for patients unsuitable for platinum-based therapy.

Last reviewed September 2017


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  1. 1.0 1.1 1.2 1.3 1.4 1.5 D'Addario G, Pintilie M, Leighl NB, Feld R, Cerny T, Shepherd FA. Platinum-based versus non-platinum-based chemotherapy in advanced non-small-cell lung cancer: a meta-analysis of the published literature. J Clin Oncol 2005 May 1;23(13):2926-36 Abstract available at
  2. 2.0 2.1 2.2 2.3 2.4 2.5 Rajeswaran A, Trojan A, Burnand B, Giannelli M. Efficacy and side effects of cisplatin- and carboplatin-based doublet chemotherapeutic regimens versus non-platinum-based doublet chemotherapeutic regimens as first line treatment of metastatic non-small cell lung carcinoma: a systematic review of randomized controlled trials. Lung Cancer 2008 Jan;59(1):1-11 Abstract available at
  3. 3.0 3.1 3.2 3.3 3.4 3.5 Li C, Sun Y, Pan Y, Wang Q, Yang S, Chen H. Gemcitabine plus paclitaxel versus carboplatin plus either gemcitabine or paclitaxel in advanced non-small-cell lung cancer: a literature-based meta-analysis. Lung 2010 Oct;188(5):359-64 Abstract available at

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Further resources

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