Influence of comorbidity on survival, toxicity and health-related quality of life in patients with advanced non-small-cell lung cancer receiving platinum-doublet chemotherapy
Introduction
Lung cancer is one of the most common malignant diseases and the leading cause of cancer-deaths worldwide. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of the cases and about half of the patients are diagnosed with advanced disease. Platinum-based chemotherapy is the recommended palliative therapy for these patients as it prolongs survival and improves health-related quality of life (HRQoL).1, 2 Such treatment is, however, often withheld from patients with significant comorbidity – especially elderly.3 One reason may be concerns about negative side-effects in terms of toxicity and deterioration of HRQoL,2, 4 although the documentation for this is scarce: in clinical trials, comorbidity is seldom systematically assessed and reported, and elderly and patients with significant comorbidity are often underrepresented.5, 6
Comorbidity increases with age,7 and due to a growing population of elderly cancer patients, there is a need to define how patients with co-existing disorders should be treated. This is particularly true for lung cancer patients; the median age is approximately 70 years,8 and as a majority have been tobacco-smokers – a well-known risk factor for a wide range of diseases – co-existing diseases are frequent.7, 9, 10
Comorbidity has been identified as an independent prognostic factor for survival in several cancers.11, 12 The results from studies of NSCLC are, however, not consistent. Whereas a negative association between the presence of comorbidity and survival has been demonstrated in studies of stage I9 and stage III10 and cohorts of mixed stages,13, 14 this has not been confirmed in advanced disease.12, 15, 16 Only a few have studied whether NSCLC-patients with severe comorbidity experience more treatment related toxicity than other patients,13, 17 and no studies have investigated the impact on HRQoL during chemotherapy in this population.
The Norwegian Lung Cancer Study Group conducted a phase III trial comparing pemetrexed plus carboplatin with gemcitabine plus carboplatin as first-line chemotherapy of advanced NSCLC.18 The aim of the present, exploratory subset analyses was to investigate whether the patients with severe comorbidity enrolled onto the study had a shorter median overall survival, experienced more toxicity or more deterioration of HRQoL during the study treatment than the patients with a better general health.
Section snippets
Approvals
The study was approved by the Regional Committee for Medical Research Ethics in Central Norway, the Norwegian Medicines Agency, the Norwegian Social Science Data Services and the Norwegian Directorate for Health and Social Affairs.
Methods and results from the main study
The methods and results of the randomised phase III trial, upon which the present subset analyses are based, have been reported previously.18 The study was designed to compare two platinum-doublet chemotherapy regimens as first-line therapy of advanced NSCLC. The
Patients
Patients who completed the baseline QLQ, received at least one cycle of chemotherapy and had copies of their hospital medical records sent to the study office (402 of the 436 patients enrolled onto the phase III trial) were analysed in the present study (Fig. 1). Age distribution and the proportion of new cases of NSCLC in Norway accrued in each age group are shown in Fig. 2A; 23% of patients <70 years and 12% of patients ⩾70 years were enrolled (p < .001).
Baseline characteristics for all patients
Discussion
None of the comorbidity-scores were significant prognostic factors for survival in our study population. This contrasts the results from previous studies of patients with localised disease and mixed cohorts of NSCLC-patients,9, 10, 12, 13, 14 but are consistent with studies of patients with metastatic disease12, elderly (⩾70 years) receiving non-platinum-chemotherapy15 and elderly (⩾65 years) receiving platinum-chemotherapy.16
A possible explanation why comorbidity does not appear to be a
Funding
The study was supported by an unrestricted grant from Eli Lilly and Company.
Role of funding source
The funding source has not influenced study design, collection of data, interpretation of data, manuscript writing or decision to submit the manuscript for publication.
Conflict of interest statement
None declared.
Writing assistance
The authors have not had any assistance in writing this manuscript.
Acknowledgements
The authors thank all the patients; the investigators within the Norwegian Lung Cancer Study Group at the following hospitals: Aker Universitetssykehus, Akershus Universitetssykehus, Ålesund Sjukehus, Hålogalandssykehuset Harstad, Hålogalandssykehuset Stokmarknes, Haugesund Sjukehus, Haukeland Universitetssykehus, Helgelandssykehuset Mosjøen, Helgelandssykehuset Sandnessjøen, Helse Finnmark – Hammerfest, Helse Finnmark – Kirkenes, Kristiansund Sykehus, Lovisenberg Diakonale Sykehus, Molde
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