Interferon Alfa With or Without Combination Chemotherapy Plus Interleukin-2 in Treating Patients With Melanoma
Interferon Alfa With or Without Combination Chemotherapy Plus Interleukin-2 in Treating Patients With Melanoma
RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Interleukin-2 may
 stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether
 interferon alfa plus combination chemotherapy and interleukin-2 is more effective than
 interferon alfa alone in treating patients with melanoma.

 PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa with or
 without combination chemotherapy plus interleukin-2 in treating patients with melanoma.
OBJECTIVES:

 -  Compare the efficacy of postoperative adjuvant therapy with interferon alfa-2b (IFN-A)
 administered subcutaneously with or without IV induction vs concurrent biochemotherapy
 including cisplatin, vinblastine, DTIC, IFN-A and IL-2 and in melanoma patients with
 regional lymph node metastases that have been surgically resected.

 -  Determine the relative toxic effects associated with adjuvant therapy with IFN-A and
 concurrent biochemotherapy including cisplatin, vinblastine, DTIC, IFN-A, and IL-2 and
 their effect on the quality of life.

 -  Determine the prognostic value of detection of melanoma cells in the peripheral blood
 using RT/PCR for tyrosinase mRNA.

 OUTLINE: This is a randomized study. All patients are stratified according to prognostic
 factors.

 Patients are randomly allocated to 1 of 2 treatment options. Treatment 1 uses interferon
 alfa-2b (IFN-A) therapy, and treatment 2 includes adjuvant biochemotherapy.

 Patients who are randomized to IFN-A will be further stratified and randomized to one of two
 interferon schedules.

 -  Schedule A: IV IFN-A induction 5 times a week for 4 weeks followed by subcutaneous IFN-A
 maintenance 3 times a week for 48 weeks.

 -  Schedule B: Subcutaneous IFN-A 3 times a week for 52 weeks. Adjuvant biochemotherapy
 begins immediately after registration on the study. Cisplatin is given IV on days 1-4;
 vinblastine is given IVPB on days 1-4; dacarbazine (DTIC) is given IVPB on day 1; IFN-A
 is given subcutaneously on days 1-5; IL-2 is given by continuous infusion for a total of
 96 hours on days 1-4. Each course of therapy is repeated every 21 days for 4 courses.
 Patients receiving adjuvant radiotherapy will start adjuvant systemic therapy within 8
 weeks from lymphadenectomy and a week after completion of and recovery from
 radiotherapy.

 PROJECTED ACCRUAL: A total of 200 patients (100 patients in each arm) will be entered.
DISEASE CHARACTERISTICS:

 -  Histologically diagnosed malignant melanoma with regional lymph node metastases

 -  Undergone complete lymph node dissection and free of any residual tumor

 -  No greater than 90 days from diagnosis of regional lymph nodes metastases

 -  No distant or resected in-transit metastases

 PATIENT CHARACTERISTICS:

 Age:

 -  10 to 66

 -  66 to 70 if in excellent physical condition

 Performance status:

 -  0-2

 Life expectancy:

 -  At least 12 months

 Hematopoietic:

 -  Hemoglobin greater than 10 g/dL

 -  WBC greater than 3,000/mm^3

 -  Platelet count greater than 100,000/mm^3

 Hepatic:

 -  Bilirubin no greater than 1.2 mg/dL

 Renal:

 -  Creatinine no greater than 1.5 mg/dL

 Other:

 -  No serious intercurrent illness that would compromise tolerance of therapy and long
 term survival

 -  Must be able to participate in follow up for minimum of 5 years

 -  No second malignancy except:

 -  In situ cervical cancer

 -  Basal or squamous skin cancer

 -  Must be able to physically and emotionally tolerate biochemotherapy

 -  No history of pulmonary or cardiac dysfunction, e.g., cardiac rhythm disturbance,
 congestive heart failure, coronary bypass, or impaired cardiac ejection fraction

 PRIOR CONCURRENT THERAPY:

 Biologic therapy:

 -  No prior immunotherapy with interferon or IL-2

 -  No concurrent immunomodulators

 Chemotherapy:

 -  No prior chemotherapy

 Endocrine therapy:

 -  No concurrent steroids

 Radiotherapy:

 -  Prior adjuvant local radiotherapy allowed for head and neck

 Surgery:

 -  No greater than 8 weeks after definitive surgery for lymph node metastases

 Other:

 -  No concurrent nonsteroid anti-inflammatory drugs, or other prostaglandin synthetase
 inhibitors