Phase II study of pemetrexed plus carboplatin in malignant pleural mesothelioma.
OBJECTIVE
This multicenter, phase II clinical study was conducted to evaluate the activity of the combination of pemetrexed and carboplatin in patients with malignant pleural mesothelioma (MPM).


METHODS
Chemotherapy-naive patients with measurable disease and adequate organ function, who were not eligible for curative surgery, received pemetrexed 500 mg/m2 and carboplatin area under the plasma concentration-time curve of 5 mg/mL/min, administered intravenously every 21 days. All patients received folic acid and vitamin B12 supplementation. Pemetrexed was provided within the Expanded Access Program.


RESULTS
A total of 102 patients were enrolled. An objective response was achieved in 19 patients (two complete and 17 partial responses), for a response rate of 18.6% (95% CI, 11.6% to 27.5%). Forty-eight patients (47.0%; 95% CI, 37.1% to 57.2%) had stable disease after treatment. Overall, 67 patients (65.7%) achieved disease control (95% CI, 55.6% to 74.8%). Median time to progression was 6.5 months; median overall survival time was 12.7 months. Compliance to treatment was excellent, with a relative dose-intensity of 97% for pemetrexed and 98% for carboplatin. Toxicity was mild, with grade 3 or 4 neutropenia occurring in 9.7% of total cycles and grade 3 or 4 anemia occurring in 3.5% of total cycles. Nonhematologic toxicity was negligible.


CONCLUSIONS
Treatment with pemetrexed and carboplatin was active and well tolerated in patients with MPM. Disease control rate, time to disease progression, and overall survival were similar to the results achieved with the standard regimen of pemetrexed and cisplatin, suggesting that the carboplatin combination could be an alternative option for these patients.
Ceresoli
Giovanni L
GL
Department of Medical Oncology and Hematology, Istituto Clinico Humanitas Istituto di Ricovero e Cura a Carattere Scientifico, Rozzano, Milan, Italy. giovanni_luca.ceresoli@humanitas.it
Zucali
Paolo A
PA
Favaretto
Adolfo G
AG
Grossi
Francesco
F
Bidoli
Paolo
P
Del Conte
Guido
G
Ceribelli
Anna
A
Bearz
Alessandra
A
Morenghi
Emanuela
E
Cavina
Raffaele
R
Marangolo
Maurizio
M
Parra
Hector J Soto
HJ
Santoro
Armando
A
D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D005971:Glutamates / Q000008:administration & dosage; D006147:Guanine / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome
D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine; D016190:Carboplatin