Guideline question: Is there a role for the use of gemcitabine in the treatment of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC)?
Objective: To make recommendations about the use of gemcitabine in the management of medically appropriate patients with stage IIIB-IV NSCLC.
Outcomes: The outcomes of interest were survival, response rate, symptomatic response, response duration and toxicity.
Perspective (values): Evidence was selected and reviewed by 2 members of the Provincial Lung Cancer Disease Site Group (DSG) of the Cancer Care Ontario Practice Guidelines Initiative. The practice guideline report was reviewed by the Provincial Lung Cancer DSG and by the Systemic Treatment Disease Site Group. These committees comprise medical and radiation oncologists, surgeons, pathologists, nurses, a psychologist, a medical sociologist and administrators. One community representative participated in the development of this practice guideline.
Quality of evidence: Five phase II studies of single-agent gemcitabine in advanced NSCLC were reviewed. Four of these are published as full reports. Two randomized phase II studies comparing single-agent gemcitabine with etoposide plus cisplatin were also reviewed. One of these studies is fully published. Seven phase II studies of gemcitabine in combination with cisplatin and I phase II study of gemcitabine in combination with ifosfamide were reviewed. Three randomized controlled trials (RCTs) and 1 randomized phase II study, published in abstract form, compared gemcitabine combination chemotherapy with cisplatin combination chemotherapy. An additional phase II study, published in abstract form, of gemcitabine as salvage therapy in previously treated patients was also included.
Benefits: Four phase II studies of single-agent gemcitabine at a dose of 1000 mg/m2 or more showed a combined response rate of 19% (intention-to-treat analysis; 95% confidence interval [CI] 15% to 24%) or 21% (efficacy analysis; 95% CI 17% to 26%) in advanced NSCLC. Median survival ranged from 7 to 9 months. Improvement from baseline in cough, hemoptysis and dyspnea was comparable to what would be expected with radiation therapy and with standard combination chemotherapy regimens. Improvement from baseline in their performance status was reported in 52% of treated patients. The 2 randomized phase II studies reported equivalent response rates for gemcitabine compared with etoposide plus cisplatin; the response data were pooled, which resulted in a nonsignificant benefit for gemcitabine (common odds ratio [OR] 0.90; 95% CI 0.43 to 1.90; p = 0.78). Gemcitabine has most frequently been combined with cisplatin, yielding a combined response rate of 44% (intention-to-treat; 95% CI 36% to 47%) or 45% (efficacy; 95% CI 39% to 51%) from 7 phase II studies. Median survival times ranged from 10