cisplatin, interferon alfa, surgery, and radiation therapy in treating patients with malignant pleural mesothelioma

Conditions: Malignant Mesothelioma

Summary: rationale: drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. radiation therapy uses high-energy x-rays to damage tumor cells. interferon alfa may interfere with the growth of cancer cells. combining chemotherapy, radiation therapy, and interferon alfa may kill more tumor cells. purpose: phase i trial to study the effectiveness of cisplatin plus interferon alfa followed by surgery and interferon alfa plus 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.

Eligibility criteria:
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

Keywords: localized malignant mesothelioma