RATIONALE: Biological therapies use different ways to stimulate the immune system and stop tumor cells from growing. Combining biological therapies with indomethacin and cyclophosphamide may kill more tumor cells.

PURPOSE: Phase II trial to compare the effectiveness of indomethacin and biological therapy with or without cyclophosphamide in treating patients who have advanced melanoma that has not responded to previous therapy.

OBJECTIVES: I. Determine whether indomethacin given prior to tumor removal can increase the number of tumor infiltrating lymphocytes (TIL) obtained from the tumor specimen of patients with advanced melanoma.

II. Determine the efficacy of administering concurrent indomethacin to maximize immune effector cell function in situ during interleukin-2/TIL therapy in these patients.

III. Determine the relationship between the phenotypic character of TIL (generated in culture from the patient's tumor) and the response to therapy.

IV. Correlate the lytic activity or lymphokine production of TIL (generated in culture from the patient's tumor) with clinical response to therapy.

V. Generate and use lymphokine-activated killer (LAK) cells in those patients who do not have TIL available for therapy and evaluate LAK cells in the same manner as TIL.

PROTOCOL OUTLINE: Patients with resectable tumors and with adequate generation of TIL are treated on Regimen A; those with unresectable tumors or insufficient TIL are treated on Regimen B.

The following acronyms are used: CTX Cyclophosphamide, NSC-26271 IL-2 Interleukin-2 (Cetus), NSC-373364 LAK Lymphokine-Activated Killer Cells TIL Tumor Infiltrating Lymphocytes

Regimen A: Prostaglandin Inhibition Therapy plus Biological Response Modifier Therapy. Indomethacin; plus CTX; IL-2-activated TIL; IL-2.

Regimen B: Prostaglandin Inhibition Therapy plus Biological Response Modifier Therapy. Indomethacin; plus IL-2-activated LAK; IL-2.

PROJECTED ACCRUAL: Up to 30 patients will be accrued over 3 years. If 0 of the first 10 patients, no more than 1 of the first 15 patients, or no more than 2 of the first 20 patients respond, accrual will cease.

Ages Eligible for Study:  17 Years and above

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically documented melanoma that is metastatic or unresectable and unresponsive to conventional chemotherapy and/or radiotherapy
• Measurable or evaluable disease required; Measurable disease defined as bidimensionally measurable lesion on physical exam, x-ray, or MRI; Evaluable disease defined as: Unidimensionally measurable lesion on x-ray, scan, or photograph; Disease assessable by serial chemistries, tumor markers, or nonspecific scans; Disease assessable by functional manifestations (e.g., change in performance status, 10% or greater change in weight); Previously irradiated lesion with subsequent disease progression documented; Bone-only lesions may be considered evaluable (lytic lesion on x-ray or bone scan should be followed)
• No metastases on CT or MRI involving more than 50% of the liver
• No uncontrolled or untreated CNS metastases

--Prior/Concurrent Therapy--

• Biologic therapy: More than 4 weeks since immunotherapy
• Chemotherapy: Prior anthracyclines allowed provided no symptomatic heart disease is present; More than 4 weeks since chemotherapy (at least 2 weeks, with recovery, if disease progression is documented); More than 6 weeks since nitrosoureas, melphalan, or mitomycin
• Endocrine therapy: More than 1 week since corticosteroids (except physiological doses for respiratory ailments or adrenal insufficiency)
• Radiotherapy: More than 4 weeks since radiotherapy (at least 2 weeks, with recovery, if disease progression is documented)
• Surgery: More than 3 weeks since major surgery (excluding surgery for tumor collection)

--Patient Characteristics--

• Age: Over 16
• Performance status: ECOG 0 or 1
• Life expectancy: At least 3 months
• Hematopoietic: (unless tumor involvement of bone marrow or spleen is documented); WBC at least 3,500/mm3; Absolute granulocyte count at least 1,500/mm3; Platelet count at least 100,000/mm3; Hemoglobin at least 11.5 g/dL; No significant hematologic abnormalities
• Hepatic: (unless tumor involvement of liver is documented); Bilirubin no greater than 1.6 mg/dL; SGOT no greater than 150 U/L; PT at least 1.5 times control; PTT less than 1.5 times control
• Renal: (unless tumor involvement of kidney is documented); Creatinine no greater than 2.0 mg/dL; Creatinine clearance at least 50 mL/min; Calcium no greater than 12 mg/dL; No symptomatic hypercalcemia
• Cardiovascular: No myocardial infarction within 6 months; No congestive heart failure; No edema; No hypotension or hypertension; No coronary artery disease; No history of arrhythmia; No contraindication to the use of pressor agents
• Pulmonary: FEV1 at least 65% of predicted
• Other: No significant organ dysfunction; No uncontrolled bacterial, viral, or fungal infection; No active peptic or duodenal ulcer; No psychiatric or seizure disorder; No prior solid organ allograft; HIV and hepatitis B surface antigen seronegative within 6 months of study entry; No second malignancy within 5 years except: Inactive nonmelanomatous skin cancer; Carcinoma in situ of the cervix; No other serious illness that would limit survival to less than 2 years; Negative pregnancy test