Single-agent gemcitabine in pretreated patients with non-small-cell lung cancer: results of an Argentinean multicentre phase II trial

Abstract

The activity and mild toxicity profile of single-agent gemcitabine therapy in untreated (chemonaive) patients with non-small-cell lung cancer (NSCLC) is well documented. This phase II trial was conducted to determine the objective tumour response rate and toxicity profile of single-agent gemcitabine in pretreated patients with NSCLC. Patients with histological evidence of advanced NCSLC stage IIIB or IV; at least one prior chemotherapy regimen including a platinum or taxane analogue; an Eastern Cooperative Oncology Group (ECOG) performance status of 0–2; clinically measurable disease; adequate bone marrow reserve; and adequate renal function; received 1000 mg m –2 gemcitabine administered over 30 min on days 1, 8 and 15 of a 28-day cycle defined as 3 weekly treatments followed by 1 week of rest. Twenty-nine patients were evaluated for efficacy and 32 for toxicity. One patient achieved a complete response and five patients had a partial response resulting in a total response rate of 20.6% (95% confidence interval (CI) 6–34). Median response duration was 7 months (range 4–11 months). Twelve (41%) patients reached stable disease after two cycles of therapy and 11 (38%) patients had disease progression. Median progression-free survival time was 3 months and median overall survival time was 5.5 months. Toxicity was generally mild (grades 0–2). Severe (grade 3 or 4) haematological toxicities included grade 3 anaemia in one patient and grade 3 thrombocytopenia in two patients. Severe non-haematological toxicities included one patient each with grade 3 liver transaminase elevations, nausea/vomiting and diarrhoea. This study confirms the activity and safety of single-agent gemcitabine in pretreated patients with advanced NSCLC who are refractory or sensitive to first-line therapy. © 1999 Cancer Research Campaign

Clinical Experience with Single-Agent Gemcitabine Chemotherapy in Patients with Non-Small-Cell Lung Cancer in Whom Previous Chemotherapy Has Failed

“…In phase II trials, the response rate to single-agent gemcitabine as second-line therapy for NSCLC has ranged from 6.0-20.6%; median survival has ranged from 4-7.9 months. [6][7][8][9][10] The present study revealed a response rate of 12.5% and a median survival of 7.5 months; these values are within the aforementioned ranges. The toxicity of single-agent gemcitabine therapy has been minimal and mild in severity, both in the present and previous studies.…”

“…The toxicity of single-agent gemcitabine therapy has been minimal and mild in severity, both in the present and previous studies. [6][7][8][9][10] The present trial also identified a median survival time of 4.5 months, together with very mild toxicity, in the 17 patients receiving gemcitabine as third-line therapy. This finding warrants further clinical study, even though median survival was shorter than that reported for daily, oral gefitinib therapy in the Iressa ® Dose Evaluation in Advanced Lung Cancer (IDEAL)-2 study, in which previous platinumbased combination chemotherapy and docetaxel regimens had also failed.…”

“…Gemcitabine probably also has activity in the secondline treatment of NSCLC, with a response rate to single-agent therapy ranging from 6.0-20.6% in phase II studies, [6][7][8][9][10] response rates in phase III trials of gemcitabine plus cisplatin versus cisplatin alone (or versus other cisplatinbased conventional regimens). 5 However, the potential roles of gemcitabine as second-and third-line chemotherapy have not been well defined.…”

Single agent gemcitabine in the second-line treatment of advanced non-small cell lung cancer after treatment with taxane + platinum regimens

“…The good results shown in our and Cho's and Crino's studies [10,11] would suggest selection of patients with good performance status is an important predictive factor of second-line gemcitabine therapy for response and longer survival. Beside performance status, it was suggested that there are also some poor prognostic factors which may affect response to second-line therapy including metastatic disease, number of metastatic sites and previous response to first-line chemotherapy [11][12][13]. In our study, although not statistically significant due to small number of patients, there was no objective response and only one stable disease in patients with more than two metastatic sites (Table 1).…”

“…Although there was no randomized study comparing single agent gemcitabine with best supportive care or other agents known to be effective in the second-line setting, its activity has been investigated in several small studies and discordant ratios of objective response ranging from 6% to 20%, 6% have been reported [10][11][12][13][14][15].…”