Influence of cisplatin-use, age, performance status and duration of chemotherapy on symptom control in advanced non-small cell lung cancer: detailed symptom analysis of a randomised study comparing cisplatin-vindesine to gemcitabine

doi:10.1016/S0169-5002(02)00515-9

Lung Cancer

Volume 40, Issue 2, May 2003, Pages 191-199

https://doi.org/10.1016/S0169-5002(02)00515-9 Get rights and content

Abstract

Background: We previously reported that treatment of patients with symptomatic advanced non-small cell lung cancer with single agent Gemcitabine (GEM) resulted in a superior clinical-benefit response rate (RR) compared to cisplatin-based combination chemotherapy. We now report the detailed individual symptom control analysis, and the influence of cisplatin-use, age, performance status (PS) and duration of treatment. Patients and methods: Patients received either GEM (1000 mg/m², days 1, 8 and 15) or cisplatin (100 mg/m², day 1) plus Vindesine (3 mg/m², days 1 and 15) (PV), both every 4 weeks. Scores of 9 symptoms were listed weekly by the patient on visual analogue scales. Improvement of a symptom was defined as 2 consecutive cycles of improvement over baseline. Results: Baseline symptoms in the 169 patients were well balanced between the 2 arms (84 GEM, 85 PV). Both patients with objective response and disease stabilisation had clearly better symptom control than those with disease progression. Symptom control in both arms was similar for ‘disease-specific’ symptoms such as cough, dyspnea, pain or haemoptysis. Compared to PV, a significantly larger number of GEM-patients had better scores for ‘constitutional’ items such as anorexia (P=0.007), ability to carry on with daily activities (P=0.04) and overall impression of quality-of-life (P=0.008). Symptom control was very similar in younger (<65 years) versus older (⩾65 years) patients, and only slightly better in those with a Karnofsky PS ⩾80% compared to those <80%. Most of the symptom improvement occurred in the first 3 cycles, with some further symptom improvement in the following cycles in the GEM-arm only. Conclusions: Both GEM and PV yield a symptom control rate much higher than expected by the objective tumour RR. GEM is equally effective in controlling ‘disease-specific’ symptoms, but superior in controlling ‘constitutional’ symptoms. Most of the symptom control was achieved during the first 3 cycles of treatment, with some further improvement thereafter in the GEM-arm only.

Introduction

Chemotherapy in advanced non-small cell lung cancer (NSCLC) results in a statistically significant, but clinically very moderate (6–8 weeks), improvement in median survival, when compared to best supportive care alone [1], [2], [3], [4]. Therefore, many other end-points besides survival have at least equal clinical interest, such as symptom control, clinical-benefit or multidimensional quality-of-life improvement.

In this regard, we have conducted a prospective, randomised, phase III study, comparing single agent Gemcitabine (GEM) to cisplatin-vindesine (PV) [5]. The primary end-point in the study was the clinical-benefit, a measurement of the patient's clinical improvement based on a combination of three very simple, but important, items: a symptom score performed by the patient, a Karnofsky performance status (PS) estimated by the physician, and the patients’ weight measured by the nurse [5]. This novel approach of measuring clinical-benefit in NSCLC did not have the ambition of becoming a full multidimensional quality-of-life instrument, but it nonetheless proved to be a very interesting tool, having the potential of avoiding laborious collection and analysis of multidimensional quality-of-life data in a multi-centre context. In this trial, GEM compared to PV was shown to result in a significantly longer lasting clinical-benefit in a significantly larger proportion of patients with symptomatic advanced NSCLC. On the other hand, there were no major differences across the 2 arms in response or survival, but GEM was characterised by significantly less grade 3 and 4 therapy-related toxicity.

We now report the detailed symptom score analysis from this randomised study. Each of the different symptoms are analysed individually, and also according to the objective tumour response rate (RR), to the treatment arm, to the patients’ age and Karnofsky PS at diagnosis, and to the duration of treatment.

Section snippets

Patients and methods

The eligibility criteria, randomisation procedure, treatment schedule, dose modifications, methods of analysis and statistics have been described in detail previously [5].

In short, eligible patients had stage IIIB (not amenable to surgery or radical radiotherapy) or stage IV NSCLC, with at least one bi-dimensionally measurable target lesion, a Karnofsky PS ⩾60%, a life expectancy ⩾3 months, and normal baseline organ functions. Patients also had to be symptomatic (see below). Exclusion criteria

Results

The overall results of the study have been reported previously [5]. In short, 84 patients were randomised to the GEM-arm, 85 to the PV-arm. The intent-to-treat objective RR was very similar in both arms: 20.2% (95%CI 11.4–29.0) for GEM versus 20.0% (95%CI 11.2–28.8) for PV. There were no significant differences between the 2 arms in time-to-progression (9.2 for GEM versus 13.7 weeks for PV, P=0.55) nor in median survival time (6.7 versus 5.5 months, P=0.13). Compared to PV, a significantly

Discussion

Detailed symptom score analysis in this randomised phase III study revealed that good symptom control was achieved both in patients with objective tumour response and disease stabilisation. GEM was equivalent to PV in ‘disease-specific’ symptom control but superior in ‘constitutional’ symptom control. Symptom improvement was not affected by age and only marginally by baseline Karnofsky PS. Most of the symptom improvement occurred in the first 3 cycles, with some further symptom improvement in

Acknowledgements

The authors want to thank Bea Anrijs and Danielle Strens, research nurses of the LLCG, for their dedicated assistance in the computer edits of the database. The authors also want to thank Nancy Dams, research nurse funded by Eli-Lilly during 3 years, for her never ending quality control of the data in the participating centres. Finally, the authors want to thank all co-investigators who entered patients in this LLCG study (in alphabetical order): J. Aumann, F. Baugnée, L. Bosquée, A. Delobbe,

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^☆: Data presented in part at the September 2000 Tokyo meeting of the International Association for the Study of Lung Cancer. PII of linked article S0169-5002(03)00074-6

¹: The other co-investigators in this LLCG trial are listed in the appendix.

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Influence of cisplatin-use, age, performance status and duration of chemotherapy on symptom control in advanced non-small cell lung cancer: detailed symptom analysis of a randomised study comparing cisplatin-vindesine to gemcitabine☆

Abstract

Introduction

Section snippets

Patients and methods

Results

Discussion

Acknowledgements

Chest

Ann. Oncol.

Eur. J. Cancer

Eur. J. Cancer

Lung Cancer

Lung Cancer

Ann. Oncol.

Lung Cancer

Lung Cancer

Lung Cancer

Polychemotherapy in advanced non-small cell lung cancer: a meta-analysis

Lancet

Chemotherapy for advanced non-small-cell lung cancer: how much benefit is enough?

J. Clin. Oncol.

Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 52 randomised clinical trials

Br. Med. J.

Reporting results of cancer treatment

Cancer

Single-agent activity of weekly gemcitabine in advanced non-small cell lung cancer: a phase II study

J. Clin. Oncol.

Effects of vinorelbine on quality of life and survival of elderly patients with advanced non-small cell lung cancer

J. Natl. Cancer Inst.

Gemcitabine and cisplatin versus mitomycin, ifosfamide, and cisplatin in advanced non-small-cell lung cancer: a randomized phase III study of the Italian lung cancer project

J. Clin. Oncol.