The evidence supporting this protocol is provided by a phase III, multicentre, randomised control trial. The trial involved 451 patients comparing doublet therapy (carboplatin and paclitaxel) with monotherapy (vinorelbine or gemcitabine) in elderly patients (over 70 years) with unresectable stage IV NSCLC or stage III disease unsuitable for radical radiation therapy and ECOG performance status 0-2.
Between April 2006 and December 2009, 451 patients from 61 centres in France were randomised to receive first line chemotherapy with either 4 cycles of doublet chemotherapy with carboplatin AUC 6 day 1 and 90mg/m2 paclitaxel on days 1, 8 and 15 every 4 weeks; or single agent chemotherapy with either 5 cycles of vinorelbine 25mg/m2 or gemcitabine 1150mg/m2 on days 1 and 8 every 3 weeks. The institution made the decision at the commencement of the study as to which single agent patients received.
Most patients were fit, with only 27% recorded with an ECOG status of 2. 80% of participants had an activities of daily living score of 6 and 75%, had Charlson comorbidity index scores of 2 or lower, thus the results cannot be extrapolated to non-fit elderly patients with poor geriatric indices.r
The primary endpoint was overall survival (OS) with secondary endpoints being progression free survival (PFS), response to first-line therapy at 6 weeks and grade 3-4 toxicities.
Patients who progressed or who were intolerant of treatment were withdrawn from the study and prescribed Erlotinib as second-line treatment if appropriate.
Platinum-based doublet chemotherapy showed a significant improvement in 1 year survival and a reduction in risk of death in comparison to single agent chemotherapy with vinorelbine or gemcitabine in elderly patients with NSCLC.r
The results of carboplatin/ paclitaxel versus monotherapy among 451 patients evaluable for response are summarised below. Subgroup analysis showed that all histological subtypes benefitted from doublet chemotherapy over monotherapy.
© The Lancet 2011
Myelosuppression is the dose limiting toxicity of carboplatin. There were significantly more grade 3-4 haematological toxicities among the patients in the doublet chemotherapy than those in the monotherapy group.r
There were 10 treatment related deaths in the doublet chemotherapy group and 3 in the monotherapy group. Primary prophylaxis with GCSF was not recommended on the study, but was authorised as secondary prophylaxis for patients who had developed grade 3-4 neutropenia. Dose reductions of carboplatin and paclitaxel should be considered if there is clinical concern about the patients' ability to tolerate the full dose.
© The Lancet 2011