Gemcitabine combined with carboplatin in patients with malignant pleural mesothelioma: a multicentric phase II study.
BACKGROUND
Malignant pleural mesothelioma (MPM) is increasing rapidly worldwide. Currently, pemetrexed plus cisplatin chemotherapy showed a survival advantage versus cisplatin alone. No impact on patient survival of surgery, radiotherapy, or their combination has been demonstrated.


METHODS
Eight centers in northeastern Italy participated in a Phase II multicenter study. Chemotherapy was comprised of carboplatin area under the concentration-time curve 5 on Day 1 and gemcitabine 1000 mg/m(2) on Days 1, 8, and 15. This cycle was repeated every 4 weeks.


RESULTS
Between July 1996 and September 2000, 50 patients were treated. Of the sample, 68% were males, 88% had a Eastern Cooperative Oncology Group performance status score of 0-1, 56% had Stage I-II disease, 68% had epithelioid histology, and 62% had no previous treatments. The delivered dose intensity of gemcitabine was 617 mg/m(2) per week, which was 82% of the planned dose (750 mg/m(2) per week). For carboplatin, the delivered dose intensity was 80 mg/m(2) per week. Overall, 44% of 15th day doses were omitted or reduced. Twenty-six percent of the patients had partial responses (95% confidence interval: 15-40%) and 24% had disease progression. None of the patients had complete responses. The median response duration was 55 weeks (range, 13-113 weeks). Patients had good clinical benefit. For example, 46% had improved dyspnea, 40% improved in weight, and 26% experienced pain reduction. Patients developed Grade 3-4 leukopenia during 18 cycles (11%) of chemotherapy. Grade 3-4 thrombocytopenia occurred more frequently, i.e., there were 24 episodes (15%) among 17 patients. Grade 3 anemia developed among patients during eight cycles (5%). None of the patients developed Grade 3-4 nonhematologic toxicity. The median survival of this sample of patients was 66 weeks with 53%, 30%, and 20% of patients alive at 1, 2, and 3 years, respectively. The median progression-free survival period was 40 weeks.


CONCLUSIONS
The gemcitabine/carboplatin combination is a valid option in the treatment of MPM due to its acceptable toxicity profile, the good response rate, and the clinical benefit to patients. Minor adjustments in schedule (3-week cycles instead of 4-week cycles) would permit a more optimal treatment administration.
Favaretto
Adolfo G
AG
Department of Medical Oncology, University Hospital, Padova, Italy. agfavaretto@yahoo.it
Aversa
Savina M L
SM
Paccagnella
Adriano
A
Manzini
Vincenzo De Pangher
Vde P
Palmisano
Valentina
V
Oniga
Francesco
F
Stefani
Micaela
M
Rea
Federico
F
Bortolotti
Luigi
L
Loreggian
Lucio
L
Monfardini
Silvio
S
D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D000093542:Gemcitabine
D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D016190:Carboplatin; D000093542:Gemcitabine