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.
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
Giovanni L
GL
Ceresoli
Paolo A
PA
Zucali
Adolfo G
AG
Favaretto
Francesco
F
Grossi
Paolo
P
Bidoli
Guido
G
Del Conte
Anna
A
Ceribelli
Alessandra
A
Bearz
Emanuela
E
Morenghi
Raffaele
R
Cavina
Maurizio
M
Marangolo
Hector J Soto
HJ
Parra
Armando
A
Santoro
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