A phase II trial of low-dose gemcitabine in a prolonged infusion and cisplatin for malignant pleural mesothelioma

Abstract

After a favorable experience with gemcitabine at a low dose in a prolonged infusion in combination with cisplatin for advanced non-small-cell lung cancer, here, we present the results from a phase II trial for patients with malignant pleural mesothelioma. Eligible patients had biopsy-proven malignant pleural mesothelioma, were chemo-naive, Eastern Cooperative Oncology Group performance status 0-2, had normal hematopoietic liver and renal function, and gave informed consent. Treatment consisted of gemcitabine 250 mg/m in a 6-h infusion on days 1 and 8 and cisplatin at 75 mg/m on day 2 of a 3-week cycle for four cycles, followed by two additional cycles without cisplatin. Seventy-eight patients (58 men, 20 women; age 33-82 years, median 58) were recruited into the trial. The histologic types were as follows: epitheloid 56 (71.8%); four sarcomatoid (5.1%); mixed 15 (19.2%); and mesothelioma, three not otherwise specified (3.8%). Grades 3-4 toxicity included two (2.6%) patients with anemia, 18 (23.1%) with neutropenia, and one with nausea/vomiting. Reversible thrombocytosis with platelets over 1000-10/l was recorded in 10 (12.8%) patients and grade 2 alopecia in 60 (76.9%). Four (5.1%) patients showed a complete response and 35 (44.9%) showed a partial response with a response rate of 39/78 (50%). Minimal response or stable disease was seen in 35 (44.9%), whereas only four (5.1%) patients progressed during treatment. Most patients reported symptomatic improvement with a higher or a stable quality of life score in 70 (89.7%) cases. The median progression-free survival was 8.0 months (confidence interval 6.9-9.0). The median overall survival was 17.0 months (confidence interval 14.7-19.2). One-year, two-year, and three-year survival rates were 67.3, 32.7, and 19.8%, respectively. Epitheloid histological type was the only statistically significant favorable prognostic factor for progression-free survival and overall survival. Because of the acceptable toxicity, remarkable activity, and reasonable cost, this treatment should be further explored.

Polymorphisms in folate pathway and pemetrexed treatment outcome in patients with malignant pleural mesothelioma

“…Studies have shown that chemotherapy significantly improves survival of patients with MPM. Randomized clinical trial has shown that treatment with combination of PMX and cisplatin improves outcome in patients with MPM7–9 and comparable results were obtained for treatment with gemcitabine and cisplatin 3,4,10…”

The influence of gemcitabine pathway polymorphisms on treatment outcome in patients with malignant mesothelioma

“…Patients were treated with gemcitabine in combination with a platinum agent according to one of the two following regimens: gemcitabine in prolonged infusion of 250 mg/m 2 over 6 h on days 1 and 8 in combination with cisplatin of 75 mg/m 2 over 1 h or carboplatin area under the curve (AUC) of 5 mg/ml/min on day 2 every 3 weeks for four cycles, followed by two cycles of gemcitabine monotherapy [32]; or gemcitabine in standard infusion of 1250 mg/m 2 over 30 min on days 1 and 8 in combination with cisplatin of 75 mg/m 2 over 1 h on day 2 every 3 weeks for four cycles, followed by two cycles of gemcitabine monotherapy. We also included patients who received gemcitabine-platinum combination chemotherapy as a part of multimodality treatment with surgery and/or palliative radiotherapy.…”

Clinical-pharmacogenetic models for personalized cancer treatment: application to malignant mesothelioma

“…3). Studies consistently show that treatment with gemcitabine/cisplatin doublet achieves comparable results67828. In Slovenian randomized phase II trial comparing pemetrexed/cisplatin and gemcitabine/cisplatin, overall median OS reached 18.6 months and there were no significant differences between groups treatment29.…”

“…A randomized clinical trial has shown that treatment with pemetrexed/cisplatin combination improved outcome in MM patients, therefore, it became the standard treatment5. Comparable results were obtained for gemcitabine/cisplatin doublet3678.…”