Gemcitabine plus best supportive care (BSC) vs BSC in inoperable non-small cell lung cancer – a randomized trial with quality of life as the primary outcome

Abstract

Three hundred patients with symptomatic, locally advanced or metastatic NSCLC not requiring immediate radiotherapy were enrolled into this randomized multicentre trial comparing gemcitabine + BSC vs BSC alone. Patients allocated gemcitabine received 1000 mg/m2on days 1, 8 and 15 of a 28-day cycle, for a maximum of six cycles. The main aim of this trial was to compare patient assessment of a predefined subset of commonly reported symptoms (SS14) from the EORTC QLQ-C30 and LC13 scales. The primary end-points were defined as (1) the percentage change in mean SS14 score between baseline and 2 months and (2) the proportion of patients with a marked (≥ 25%) improvement in SS14 score between baseline and 2 months sustained for ≥4 weeks. The secondary objectives were to compare treatments with respect to overall survival, and multidimensional QL parameters.The treatment groups were balanced with regard to age, gender, Karnofsky performance status (KPS) and disease stage (40% had metastatic disease). The percentage change in mean SS14 score from baseline to 2 months was a 10% decrease (i.e. improvement) for gemcitabine plus BSC and a 1% increase (i.e. deterioration) for BSC alone (P = 0.113, two-sample t -test). A sustained (≥ 4 weeks) improvement (≥25%) on SS14 was recorded in a significantly higher proportion of gemcitabine + BSC patients (22%) than in BSC alone patients (9%) (P = 0.0014, Pearson’s chi-squared test). The QLQ-C30 and L13 subscales showed greater improvement in the gemcitabine plus BSC arm (in 11 domains) than in the BSC arm (one symptom item). There was greater deterioration in the BSC alone arm (six domains/items) than in the gemcitabine + BSC arm (three QL domains). Tumour response occurred in 19% (95% CI 13–27) of gemcitabine patients. There was no difference in overall survival: median 5.7 months (95% CI 4.6–7.6) for gemcitabine + BSC patients and 5.9 months (95% CI 5.0–7.9) (log-rank, P = 0.84) for BSC patients, and 1-year survival was 25% for gemcitabine + BSC and 22% for BSC. Overall, 74 (49%) gemcitabine + BSC patients and 119 (79%) BSC patients received palliative radiotherapy. The median time to radiotherapy was 29 weeks for gemcitabine + BSC patients and 3.8 weeks for BSC. Patients treated with gemcitabine + BSC reported better QL and reduced disease-related symptoms compared with those receiving BSC alone. These improvements in patient-assessed QL were significant in magnitude and were sustained. © 2000 Cancer Research Campaign

Gemcitabine with either paclitaxel or vinorelbine vs paclitaxel or gemcitabine alone for elderly or unfit advanced non-small-cell lung cancer patients

“…Single agent paclitaxel was also demonstrated to produce a 2-month longer MST (6.8 vs 4.8 months) in comparison with supportive care in a randomised trial with no upper limit of age for accrual (Ranson, 2000), and this drug appeared highly attractive for treating elderly patients, in view of the increasing evidence that a weekly schedule may improve its toxicity profile (Alberola et al, 2002). Furthermore, retrospective (Martin et al, 1997;Shepherd et al, 1997) and prospective studies (Altavilla et al, 2000;Anderson et al, 2000;Ricci et al, 2000) have also supported the use of gemcitabine in elderly NSCLC patients, given its good tolerability and activity regardless of age.…”

Chemotherapy and quality of life in advanced NSCLC

“…The chemotherapy regimens were single agent gemcitabine, paclitaxel, vinorelbine in a selected elderly population, the combination mitomycin C, ifosfamide and cisplatin (MIC) and single agent docetaxel (Cullen et al, 1999; the Elderly Lung Cancer Vinorelbine Italian Study Group, 1999;Anderson et al, …”

“…The study reported by Anderson et al (2000) in the August issue of the BJC demonstrated a sustained improvement in symptom score with corresponding improvement in QOL, when gemcitabine (GC) was combined with best supportive care (BSC) vs BSC alone in advanced NSCLC. Although GC produced an objective response rate of 19%, with fewer patients requiring radiotherapy (RT); and the time to RT salvage was longer with GC, there was no difference in survival.…”

Meta-analysis of single agents in the chemotherapy of NSCLC: what do we want to know?

“…Clinical benefit is evidenced from phase III randomized trials showing survival, symptomatic and quality of life benefits (Non-small Cell Lung Cancer Collaborative Group, 1995;Cullen et al, 1999;Anderson et al, 2000). The optimal chemotherapeutic regimen and the magnitude of benefit in day-to-day clinical practice however remains controversial.…”

“…These have shown an economic advantage for patients treated with chemotherapy over the cost of patients who received supportive care alone (Jaakkimainen et al, 1990;Anderson et al, 2000). More recent work has shown significant differences in the costs associated with different regimens (Berthelot et al, 2000).…”