A phase II trial of low-dose gemcitabine in a prolonged infusion and cisplatin for malignant pleural mesothelioma.
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.
Institute of Oncology Ljubljana, Zaloska, Ljubljana. vkovac@onko-i.si
Viljem
V
Kovac
Matjaz
M
Zwitter
Mirjana
M
Rajer
Aleksander
A
Marin
Andrej
A
Debeljak
Uros
U
Smrdel
Martina
M
Vrankar
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D011788:Quality of Life; D017524:Slovenia / Q000453:epidemiology; D000093542:Gemcitabine
D003841:Deoxycytidine; D002945:Cisplatin; D000093542:Gemcitabine