Elsevier

European Journal of Cancer

Volume 46, Issue 12, August 2010, Pages 2225-2234
European Journal of Cancer

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

https://doi.org/10.1016/j.ejca.2010.04.009Get rights and content

Abstract

Aim of the study

To investigate whether patients with severe comorbidity receiving platinum-based chemotherapy for advanced non-small-cell lung cancer (NSCLC) have a shorter overall survival, experience more toxicity or more deterioration of health-related quality of life (HRQoL) than other patients during treatment.

Patients and methods

Patients enrolled onto a phase III trial comparing pemetrexed/carboplatin with gemcitabine/carboplatin as first-line therapy of stage IIIB/IV NSCLC were analysed. Eligible patients had performance status 0–2 and adequate kidney/liver/bone-marrow function. Comorbidity was assessed from hospital medical records using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G). Toxicity was graded using the CTCAE v3.0 and the patients reported HRQoL on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30/LC13.

Results

Data from 402 of the 436 of the patients enrolled onto the phase III trial were analysed. The patients with severe comorbidity had similar survival as other patients (6.9 versus 8.1 months; p = .34), similar frequency of neutropenia (48% versus 42%; p = .16), but experienced more neutropenic fevers (12% versus 5%; p = .012) and deaths from neutropenic infections (3% versus 0%; p = .027). They had more thrombocytopenia (46% versus 36%; p = .03), but not more thrombocytopenic bleedings (3% versus 4%; p = .65). In general, the patients with severe comorbidity reported poorer HRQoL, but not significantly more deterioration of HRQoL.

Conclusions

The results from our study suggest that patients with advanced NSCLC who have severe co-existing disorders benefit from and tolerate platinum-doublet chemotherapy as well as other patients. They do, however, appear to have a higher risk of acquiring infections when neutropenic.

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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