title: Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the treatment of advanced malignant pleural mesothelioma: a Phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP).
abstract: BACKGROUND
  The cisplatin-doxorubicin combination has shown moderate activity in malignant pleural mesothelioma (MPM; objective response, 25%), and preclinical studies suggest that interferons (IFNs) may have an antiproliferative effect on mesothelioma cell lines with a marked increase in cisplatin cytotoxicity. Therefore, the combined chemoimmunotherapy regimen is an worthwhile approach to evaluate in a Phase II trial.
  
  
  METHODS
  From December 1995 to June 1999, 37 previously untreated patients with MPM were treated with cisplatin 60 mg/m(2) intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and IFN-alpha-2b, 3 x 10((6)) international units subcutaneously 3 times a week for a total of 6 courses or until progression. Inclusion criteria were histologic diagnosis of MPM and measurable disease defined by computed tomography scan or magnetic resonance imaging.
  
  
  RESULTS
  Thirty-four patients were assessable for toxicity and 35 for efficacy according to World Health Organization criteria. One hundred thirty-five courses were administered with a median of 4 cycles per patients. Seventy-six percent of patient presented at least 1 episode of severe myelosuppression (Grade 3 and 4). Severe anemia and thrombocytopenia occurred in 30% and 24% of patients, respectively. Sixty percent of patients presented constitutional symptoms. In the 35 patients assessable for response, the overall response rate was 29% (95% confidence interval, 15-47%). The median duration of response was 8.4 months. With a median follow-up of 19.6 months, the median survival was 9.3 months. One- and 2-year survival was 45% and 34%, respectively.
  
  
  CONCLUSIONS
  This combined regimen has definite activity in MPM. However, toxicity, particularly myelosuppression and fatigue, is not negligible and may limit its application.
authors.affiliation: Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Via Manzoni 56, 20089 Rozzano-Milano, Italy. hector.sotoparra@humanitas.it
authors.forename: H S
authors.initials: HS
authors.lastname: Parra
authors.forename: L
authors.initials: L
authors.lastname: Tixi
authors.forename: F
authors.initials: F
authors.lastname: Latteri
authors.forename: S
authors.initials: S
authors.lastname: Bretti
authors.forename: M
authors.initials: M
authors.lastname: Alloisio
authors.forename: A
authors.initials: A
authors.lastname: Gravina
authors.forename: R
authors.initials: R
authors.lastname: Lionetto
authors.forename: P
authors.initials: P
authors.lastname: Bruzzi
authors.forename: C
authors.initials: C
authors.lastname: Dani
authors.forename: R
authors.initials: R
authors.lastname: Rosso
authors.forename: M
authors.initials: M
authors.lastname: Cosso
authors.forename: L
authors.initials: L
authors.lastname: Balzarini
authors.forename: A
authors.initials: A
authors.lastname: Santoro
authors.forename: A
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D009367:Neoplasm Staging; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011994:Recombinant Proteins; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D004317:Doxorubicin; D002945:Cisplatin