Combined cisplatin, doxorubicin, and mitomycin for the treatment of advanced pleural mesothelioma: a phase II FONICAP trial. Italian Lung Cancer Task Force.
BACKGROUND
In a previous FONICAP trial, the combination of doxorubicin (D) and cisplatin (P) yielded an objective response rate of 25% and a subjective response rate of 50% in patients with mesothelioma. In human mesothelioma cell lines, mitomycin (M) showed a synergic activity with P and in a recent randomized study, the combination of M and P showed slightly superior activity when compared with the PD regimen.


METHODS
The authors tested the activity and toxicity of a combination chemotherapy regimen including P, 60 mg/m2, D, 60 mg/m2, and M, 10 mg/m2, all by intravenous infusion on Day 1 every 28 days in a Phase II study.


RESULTS
Twenty-four chemotherapy-naive mesothelioma patients were enrolled in the study. Patient characteristics were the following: the median age was 58 years; the median performance status was 1; there were 6 Stage I patients, 15 Stage II patients, 2 Stage III patients, and 1 Stage IV patient; and 10 patients had previous asbestos exposure. All patients had pretreatment symptoms: 13 had chest pain, 9 had pleural effusion, and 7 had dyspnea. A total of 78 cycles of chemotherapy were administered. The only significant side effect was myelosuppression, with only 9.5% of patients having Grade 4 toxicity. Among 23 patients evaluable for response, 5 achieved a partial response (20.8%; 95% confidence interval, 7.1-42.1%), 9 had stable disease, and 9 had progressive disease (including 1 early death). One patient was not evaluable because of treatment refusal. A clinical improvement was observed in 7 of 24 patients (29%).


CONCLUSIONS
The combination of PDM in patients with pleural mesothelioma is feasible and moderately active. However, the observed level of activity is similar to that obtained with other two-drug regimens.
Pennucci
M C
MC
Division of Medical Oncology I, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
Ardizzoni
A
A
Pronzato
P
P
Fioretti
M
M
Lanfranco
C
C
Verna
A
A
Giorgi
G
G
Vigani
A
A
Frola
C
C
Rosso
R
R
D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001853:Bone Marrow / Q000187:drug effects; D002637:Chest Pain / Q000473:pathology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D018450:Disease Progression; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D004417:Dyspnea / Q000473:pathology; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy*; D008875:Middle Aged; D008937:Mitomycins / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D016066:Pleural Effusion, Malignant / Q000473:pathology; D010997:Pleural Neoplasms / Q000188:drug therapy*; D012074:Remission Induction
D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D008937:Mitomycins; D004317:Doxorubicin; D002945:Cisplatin