Malignant Mesothelioma
Conditions
Keywords
localized malignant mesothelioma
Brief 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.
Detailed description
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.
Interventions
BIOLOGICALrecombinant interferon alfa
vaccine
DRUGcisplatin
PROCEDUREsurgical procedure
RADIATIONradiation therapy
Sponsors
National Cancer Institute (NCI)
Fox Chase Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Countries
United States
Outcome results
None listed