Patient case: 69-year-old female with melanoma; genetic feature: high serum LDH levels

Clinical trial: S0008: Chemotherapy Plus Biological Therapy in Treating Patients With Melanoma

Summary: 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.

Detailed description: 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: 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

Relevance to patient case: not relevant