Sequential chemotherapy with cisplatin/gemcitabine (CG) followed by mitoxantrone/methotrexate/mitomycin (MMM) in patients with malignant pleural mesothelioma. A multicenter Italian Phase II Study (SITMP1).
OBJECTIVE
We performed a multicenter phase II trial to evaluate the impact on the activity, efficacy, symptom control and safety of using two active regimens in a sequential schedule (cisplatin/gemcitabine followed by mitoxantrone/methotrexate/mitomycin) as first-line chemotherapy for unresectable malignant pleural mesothelioma (MPM).


METHODS
A total of 54 patients received cisplatin 75 mg/m(2) on day 1 and gemcitabine 1,200 mg/m(2) on days 1 and 8, every 3 weeks for four courses (CG regimen) followed by mitoxantrone 10 mg/m(2) on day 1, methotrexate 35 mg/m(2) on day 1 and mitomycin 7 mg/m(2) on day 1, every 3 weeks with mitomycin in alternate cycles for four courses (MMM regimen).


RESULTS
We observed 3 complete responses (CRs) (5.6%) and 13 partial responses (PRs) (24.0%), with an overall response rate (ORR) of 29.6% (95% confidence interval, 17-42%), 33 stable disease (SD) (61.1%) and 5 progressive disease (PD) (9.2%). Median time to progression (TTP) was 9.5 months (range, 2-23). Median overall survival (OS) was 13 months (range, 3-33); 1-year survival rate was 63%. The treatment produced a good symptom control, with an improvement during chemotherapy in dyspnea and pain in 52.9 and 48.3% of patients, respectively. The major toxicity observed was hematological. Grades 3-4 NCI-CTC v 2.0 toxicity with the CG regimen included: neutropenia (11.1%), anemia (1.9%), thrombocytopenia (7.4%), vomiting (11.1%) and with the MMM regimen: neutropenia (35.2%), anemia (5.5%), thrombocytopenia (7.4%) and stomatitis (1.9%).


CONCLUSIONS
This phase II study with the sequential approach of two active regimens showed a good disease control in MPM, with symptom improvement and only mild toxicity.
Pinto
Carmine
C
Unit of Medical Oncology, S. Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna, Italy. cpinto@aosp.bo.it
Marino
Antonella
A
De Pangher Manzini
Vincenzo
V
Benedetti
Giovanni
G
Galetta
Domenico
D
Mazzanti
Paola
P
Del Conte
Guido
G
dell'Amore
Davide
D
Piana
Edera
E
Giaquinta
Stefania
S
Lopez
Massimo
M
Martoni
Andrea
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007558:Italy; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000473:pathology; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D016685:Mitomycin / Q000627:therapeutic use; D008942:Mitoxantrone / Q000627:therapeutic use; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000473:pathology; D012189:Retrospective Studies; D016896:Treatment Outcome; D000093542:Gemcitabine
D003841:Deoxycytidine; D016685:Mitomycin; D008942:Mitoxantrone; D002945:Cisplatin; D008727:Methotrexate; D000093542:Gemcitabine