Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer

doi:10.1016/S0169-5002(99)00067-7

Lung Cancer

Volume 26, Issue 2, November 1999, Pages 85-94

https://doi.org/10.1016/S0169-5002(99)00067-7 Get rights and content

Abstract

This randomized study was designed to determine the response rates, survival and toxicities of single-agent gemcitabine (GEMZAR™) and a combination of cisplatin/etoposide in chemonaive patients with non-resectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Gemcitabine 1000 mg/m² was given as a 30-min intravenous infusion on days 1, 8, 15 of a 28-day cycle, cisplatin 100 mg/m² on day 1, and etoposide 100 mg/m² on days 1 (following cisplatin), 2 and 3. Major eligibility criteria included histologically confirmed non-small cell lung cancer, measurable disease, Zubrod performance status 0–2, no prior chemotherapy, no prior radiation of the measured lesion, and no CNS metastases. One hundred and forty-seven patients were enrolled, 72 in the gemcitabine and 75 in the cisplatin/etoposide arm. Patient characteristics were well-matched across both arms. Sixty-seven gemcitabine and 72 cisplatin/etoposide patients were qualified for efficacy analysis. There were no complete responses, but 12 partial responses in the gemcitabine arm and 11 in the cisplatin/etoposide arm, for protocol-qualified response rates of 17.9% (95% CI: 9.6–29.2%) and 15.3% (95% CI: 7.9–25.7%), respectively. Median survival times were 6.6 months (95% CI: 4.9–7.3 months) for gemcitabine and 7.6 months (95% CI: 5.4–9.3 months) for cisplatin/etoposide. The 1-year survival probability estimate was 26% for gemcitabine and 24% for cisplatin/etoposide. There were no statistically significant between-group differences in time-to-event measures, but patients in the gemcitabine arm had a greater probability of achieving a tumour response after 2 months (probability estimate: 8 vs. 0%) and of the response lasting at least 6 months (73 vs. 45%). Clinical and haematologic toxicity was more pronounced in the cisplatin/etoposide arm. Quality-of-life measures indicated a significant worsening of symptomatology in the cisplatin/etoposide arm for hair loss, nausea and vomiting, and appetite loss. This randomized study provides further evidence that single-agent gemcitabine is an active and effective therapy for patients with non-resectable, locally advanced or metastatic NSCLC and good performance status, and that it is better tolerated than the combination cisplatin/etoposide.

Introduction

This paper presents the final analyses from a randomized, Phase II study designed to compare the response rate, survival and toxicity of single-agent gemcitabine (GEMZAR™) with a combination of cisplatin/etoposide, in chemonaive patients with non-resectable, locally advanced or metastatic non-small cell lung cancer (NSCLC). Cisplatin/etoposide was chosen as the comparator because it is frequently used, and is a recommended cisplatin-based treatment for patients with this disease [16].

The results update previously published interim data [15].

The rationale for the study is based on evidence from Phase II studies [1], [2], [11] showing that gemcitabine produces comparable response rates (around 20%—verified by external review) and median survival (8.9 months) to cisplatin/etoposide (response range: 20%–30%, median survival of 4–10.5 months [18], [19], [8], [9], [12], [13], [22]), but a better toxicity profile, particularly with respect to dose-limiting haematologic toxicity.

By providing an active and better tolerated therapy to current cisplatin-based combinations, gemcitabine may satisfy the needs of oncologists who believe that the small gains in survival conferred by chemotherapy do not warrant the considerable toxicity burden and reduction in quality of life suffered by patients with advanced NSCLC. Further, the increased practicality and potential for outpatient treatment with less need for supportive care offered by a single-agent therapy should meet the needs of cash-limited healthcare agencies, while further enhancing patient quality of life.

Section snippets

Study and design

This was an open-label, multicentre, randomized Phase II study designed to make a simultaneous evaluation of the efficacy and tolerability of single-agent gemcitabine and cisplatin/etoposide combination therapy in chemonaive patients with locally advanced or metastatic NSCLC. Secondary objectives included an evaluation of changes in quality of life, disease-related symptoms, and time-to-event efficacy parameters such as overall patient survival, duration of response, time to progressive disease

Patient demographics and baseline characteristics

A total of 147 patients were enrolled between June and December 1995. Of these, 72 (53 male, 19 female) were randomized to the gemcitabine treatment arm and 75 (61 male, 14 female) to the cisplatin/etoposide arm. Patient demographics and baseline disease characteristics were well-matched across treatment arms (Table 1), although there were slightly more (16.7 vs. 9.3%) patients in the gemcitabine arm with a Zubrod performance status of 2. The majority of patients enrolled had a performance

Discussion

The goal of chemotherapy for the treatment of locally advanced or metastatic NSCLC is to maximize survival while maintaining an acceptable standard of patient quality of life. The current recommended treatment for NSCLC is cisplatin-based combination therapy.This recommendation is based on studies suggesting that this therapy produces a higher response rate and slightly longer survival compared to single-agent therapy [16]. However, cisplatin-based chemotherapy is associated with high levels of

Acknowledgements

This study was supported by Eli Lilly and Company.

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Single-agent gemcitabine: an active and better tolerated alternative to standard cisplatin-based chemotherapy in locally advanced or metastatic non-small cell lung cancer

Abstract

Introduction

Section snippets

Study and design

Patient demographics and baseline characteristics

Discussion

Acknowledgements

Eur. J. Cancer.

Eur. J. Cancer. Clin. Oncol.

Eur. J. Cancer

Efficacy and safety profile of gemcitabine in non-small cell lung cancer: a phase II study

J. Clin. Oncol.

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

J. Clin. Oncol.

Phase II trial of acivicin versus etoposide-cisplatin in non-small cell lung cancer. An Eastern Cooperative Oncology Group study

Am. J. Clin. Oncol.

Combination chemotherapy versus single agents followed by combination chemotherapy in stage IV non-small cell lung cancer: a study of the Eastern Oncology Group

J. Clin. Oncol.

Randomized trial of three combinations of cisplatin with vindesine and/or VP-16 in the treatment of advanced NSCLC

J. Clin. Oncol.

Random prospective study of vindesine versus vindesine plus cisplatin, plus mitomycin in advanced non-small cell lung cancer

J. Clin. Oncol.