Cisplatin, Interferon Alfa, Surgery, and Radiation Therapy in Treating Patients With Malignant Pleural Mesothelioma

OBJECTIVES: I. Determine the maximum tolerated dose (MTD) of neoadjuvant interferon alfa 2b (IFN-A2b) administered with cisplatin in patients with malignant pleural mesothelioma. II. Determine the MTD of IFN-A2b administered with radiation therapy and cisplatin after surgery in these patients. III. Determine the response rate and toxicity of induction therapy with IFN-A2b and cisplatin in these patients. IV. Determine the toxicity of concurrent radiation therapy, cisplatin, and IFN-A2b after surgery in these patients. V. Determine the local control rate, freedom from progression, median survival, and long term survival of these patients after combined modality therapy.

OUTLINE: This is a dose escalation study. Patients receive induction therapy consisting of cisplatin IV weekly and interferon alfa 2b (IFN-A2b) subcutaneously three times a week for 6 weeks. Patients who experience at least 25% tumor shrinkage receive another 4 weeks of therapy. Patients then undergo debulking surgery to remove all gross tumor, if possible. If this resection is performed, then patients begin radiation therapy 2-6 weeks after surgery. Patients with unresectable tumors begin radiation therapy 2-4 weeks after the last course of induction chemotherapy. Patients undergo radiation therapy 5 days a week for 6 weeks. Concurrently, patients receive cisplatin IV weekly and IFN-A2b subcutaneously three times a week. Cohorts of 4 patients each receive escalated doses of IFN-A2b during induction chemotherapy. Once the maximum tolerated dose (MTD) of IFN-A2b is established, one dose level below this dose is used for the beginning doses of IFN-A2b during adjuvant chemotherapy. If no unacceptable toxic effects occur, then the dose of IFN-A2b is escalated to the induction MTD. Patients are followed at 3-6 weeks after completing radiochemotherapy, then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 25 patients will be accrued for this study within 2-3 years.

DISEASE CHARACTERISTICS:

• Histologically proven ipsilateral malignant pleural mesothelioma
• No contralateral thoracic or intra-abdominal involvement
• No distant metastases

PATIENT CHARACTERISTICS:

• Age: 18 and over
• Performance status: ECOG 0 or 1
• Life expectancy: Not specified
• Hematopoietic:

• Absolute neutrophil count greater than 2,000/mm3
• Platelet count greater than 100,000/mm3
• No symptomatic anemia requiring transfusion
• Hepatic:

• Bilirubin less than 2.0 mg/dL
• No autoimmune hepatitis
• No history of decompensated liver disease; e.g. esophageal varices
• Ascites
• Albumin at least 2.5 mg/dL
• Increasing prothrombin time of at least 2.0
• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular:

• No symptomatic or debilitating cardiovascular disease,
• No concurrent thrombophlebitic or embolic disorders
• Pulmonary:

• No symptomatic or debilitating pulmonary disease,
• Pretreatment diffusion capacity greater than 30% of predicted normal
• Projected post-treatment FEV1 at least 1.0 L
• Other:

• No prior malignancy within 3 years, except nonmelanomatous skin cancer
• Carcinoma in situ of the cervix
• Ductal carcinoma in situ of the breast
• Not pregnant
• Fertile patients must use effective contraception
• No history of hypersensitivity to interferon or any component of the injection
• No uncontrolled diabetes (blood sugars consistently at least 300 mg/dL)
• No insulin dependent diabetes mellitus with history of ketoacidosis within 1 year
• No psychosis
• No uncontrolled thyroid abnormalities
• No active infection requiring intravenous antibiotics

PRIOR CONCURRENT THERAPY:

• Biologic therapy: No prior biologic therapy
• Chemotherapy: No prior chemotherapy
• Endocrine therapy: Not specified
• Radiotherapy: No prior radiotherapy
• Surgery:

• No prior debulking surgery
• No prior chest tube drainage with sclerosis if tumor resectable
• Prior thoracentesis allowed