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)

Lung Cancer. 2006 Mar 14; [Epub ahead of print] [Link]

Carmine Pintoa, Antonella Marinoa, Vincenzo De Pangher Manzinib, Giovanni Benedettic, Domenico Galettad, Paola Mazzantie, Guido Del Contef, Davide dell’Amoreg, Edera Pianaa, Stefania Giaquintaa, Massimo Lopezh and Andrea Martonia

aUnit of Medical Oncology, S. Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna, Italy
bUnit of Medical Oncology, Civic Hospital, Monfalcone and Gorizia, Italy
cUnit of Medical Oncology, Bellaria Hospital, Bologna, Italy
dUnit of Medical and Experimental Oncology, IRCCS, Bari, Italy
eUnit of Medical Oncology, Torrette Hospital, Ancona, Italy
fUnit of Medical Oncology, Maggiore Hospital, Trieste, Italy
gUnit of Thoracic Surgery, Morgagni-Pierantoni Hospital, Forlì, Italy
hUnit of Medical Oncology, Regina Elena Institute, Rome, Italy

Received 12 October 2005;  revised 11 January 2006;  accepted 17 January 2006.  Available online 20 March 2006.


Purpose:  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).

Patients and methods: A total of 54 patients received cisplatin 75 mg/m2 on day 1 and gemcitabine 1200 mg/m2 on days 1 and 8, every 3 weeks for four courses (CG regimen) followed by mitoxantrone 10 mg/m2 on day 1, methotrexate 35 mg/m2 on day 1 and mitomycin 7 mg/m2 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%).

Conclusion: 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.

Keywords: Cisplatin/gemcitabine; Mitoxantrone/methotrexate/mitomycin; Phase II study