S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma

RATIONALE: Interferon alfa may interfere with the growth of cancer cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Interleukin-2 may stimulate a person's white blood cells to kill melanoma cells. It is not yet known whether interferon alfa is more effective with or without combination chemotherapy and interleukin-2 for melanoma.

PURPOSE: Randomized phase III trial to compare the effectiveness of interferon alfa with or without combination chemotherapy consisting of cisplatin, vinblastine, and dacarbazine, plus interleukin-2, in treating patients who have melanoma.

OBJECTIVES:

* Compare the overall survival and disease-free survival of patients with high-risk melanoma treated with interferon alfa vs cisplatin, vinblastine, and dacarbazine plus interferon alfa and interleukin-2.
* Compare the toxic effects of these treatment regimens in these patients.
* Determine the relationship between minimal residual disease (MRD) status at 12 weeks and 52 weeks and overall survival of patients treated with these regimens.
* Compare the effects of these treatment regimens on the MRD status of these patients.
* Determine the relationship between clinical characteristics (number of involved lymph nodes, ulcerated primary, and extracapsular extension) and MRD in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to nodal status (N1 or N2 vs N3), degree of lymph node involvement (micrometastases only vs any macrometastases, including satellite/in-transit metastases), and ulceration of the primary tumor (yes vs no vs unknown primary). Patients are randomized to 1 of 2 treatment arms.

* Arm I: Patients receive interferon alfa IV on days 1-5 of weeks 1-4 followed by interferon alfa subcutaneously (SC) on days 1, 3, and 5 of weeks 5-52 in the absence of disease progression or unacceptable toxicity.
* Arm II: Patients receive cisplatin IV over 30 minutes followed by vinblastine IV on days 1-4. Patients also receive dacarbazine IV over 1 hour on day 1, interleukin-2 IV over 96 hours on days 1-4, and interferon alfa SC on days 1-5, 8, 10, and 12. In addition, patients receive filgrastim (G-CSF) SC on days 6-15. Treatment repeats every 3 weeks for 3 courses in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually for 5 years.

PROJECTED ACCRUAL: A total of 410 patients (205 per treatment arm) will be accrued for this study within 3 years.

Eligibility Criteria:
DISEASE CHARACTERISTICS:

* Histologically proven melanoma of cutaneous origin or from unknown primary at initial presentation of primary or first clinically detected nodal or satellite/in-transit recurrence

  * No distant metastases
  * No melanoma of ocular, mucosal, or other non-cutaneous origin
* One of the following criteria must apply for patients with newly diagnosed melanoma OR a previously diagnosed primary with current subsequent, clinical, regional nodal disease and/or satellite/in-transit disease:

  * Ulcerated primary melanoma with 1 or more involved lymph nodes (micro/occult or macro/clinically overt)
  * Non-ulcerated or unknown primary melanoma with one macro/clinically overt lymph node metastasis, including a single matted nodal mass

    * No non-ulcerated or unknown primary tumor and a single micrometastatic lymph node
  * Non-ulcerated melanoma with two or more lymph node metastases (micro/occult or macro/clinically overt) and/or matted nodes
  * Any satellite/in transit metastasis with or without lymph node involvement
* Patients with recurrent disease must have recurrent disease in the regional nodal basin of a prior complete lymphadenectomy
* Multiple regional nodal basin involvement allowed if they are appropriate anatomic drainage basins for primary site
* Patients must be disease free at time of enrollment based on the following surgical criteria:

  * Patients at initial presentation of melanoma must undergo adequate wide excision of primary lesion
  * Patients with previously diagnosed melanoma must have all disease resected with pathologically negative margins and no disease at primary site or second resection of primary
  * Full lymphadenectomy required of all patients including those with positive sentinel nodes or positive satellite/in-transit metastasis
* No more than 56 days since prior lymphadenectomy OR surgery to remove recurrent disease after prior complete lymphadenectomy
* Must be willing to participate in minimal residual disease studies if registered on the study on 3/1/2003 or later

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Zubrod 0-1

Life expectancy:

* Not specified

Hematopoietic:

* Absolute granulocyte count at least 1,500/mm\^3
* Platelet count at least 100,000/mm\^3

Hepatic:

* Bilirubin no greater than 1.5 times upper limit of normal (ULN)
* SGOT or SGPT no greater than 2 times ULN
* LDH and alkaline phosphatase no greater than 2 times ULN (above normal value requires a contrast-enhanced CT scan or MRI of liver)
* No known recent hepatitis positivity by PCR

Renal:

* Creatinine no greater than 1.5 mg/dL OR
* Creatinine clearance at least 75 mL/min

Cardiovascular:

* No congestive heart failure
* No coronary artery disease
* No serious cardiac arrhythmia
* No prior myocardial infarction
* Normal cardiac stress test required if any of the following are present:

  * Over age 50
  * Abnormal EKG
  * History of cardiac disease

Pulmonary:

* No symptomatic pulmonary disease

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No autoimmune disorders or conditions of immunosuppression
* No other prior malignancy within the past 5 years except the following:

  * Adequately treated basal cell or squamous cell skin cancer
  * Carcinoma in situ of the cervix
  * Adequately treated stage I or II cancer in remission
* HIV negative
* No known AIDS or HIV-1 associated complex

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* No prior immunotherapy, including interferon, interleukin, levamisole, or other biologic response modifiers
* No other concurrent biologic therapy

Chemotherapy:

* No prior chemotherapy (including infusion or perfusion therapy)
* No other concurrent chemotherapy

Endocrine therapy:

* No concurrent systemic corticosteroids or topical steroid creams
* Concurrent steroid antihistamines allowed if no alternative
* No concurrent hormonal therapy

Radiotherapy:

* No prior radiotherapy

  * Prior postlumpectomy radiotherapy for breast cancer allowed
* No concurrent radiotherapy

Surgery:

* See Disease Characteristics
* No concurrent surgery

Other:

* No concurrent anti-hypertensive medications (arm II only)
* No concurrent immunosuppressive agents
* No other concurrent anticancer therapy
* Antihistamines allowed if no alternative medication suitable