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