Phase II trial of subcutaneous interferon followed by intravenous hybrid bolus/continuous infusion interleukin-2 in the treatment of renal cell carcinoma: final results of Cancer Biotherapy Research Group 95-09.

OBJECTIVE: We conducted a phase II trial in metastatic renal cell cancer of outpatient subcutaneous (s.c.) interferon-alpha2b (IFN), followed by an inpatient hybrid schedule of bolus and continuous interleukin-2 (IL- 2). METHODS: Treatment consisted of monthly IFN 10 MU/m(2) s.c. for 4 consecutive days, followed by 36 MIU/m(2) bolus IL-2, then 72-hour continuous intravenous (i.v.) infusion of 18 MIU/m(2) IL-2 per day. Between May 1997 and June 2000, 25 men and 11 women enrolled, with a median age of 57 years (range, 42-77), including 9 patients over 65. Prior treatment included nephrectomy (31), radiation (8), biotherapy (7), and chemotherapy (4). Sites of disease included 26 lung, 13 lymph node, 9 bone, 8 liver, 4 kidney, and 4 adrenal locations. Patients received an average of 3.1 treatment cycles (range, 1-6). RESULTS: There was 1 complete and 3 partial responses, for a response rate of 11% (3% to 27%; 95% confidence interval [CI]); 40% had stable disease. Median failure-free survival was 2.5 months; median overall survival was 15.0 months. The 1-, 2-, and 5-year survival rates were 53%, 30%, and 12%, respectively. Only 8 patients required a reduction in IL-2 dose. The most frequent grade 3 or 4 toxicities were 11% fatigue, 9% renal insufficiency, and 7% hypotension. CONCLUSIONS: Response and survival rates were similar to those seen in other multicenter trials using inpatient high-dose IL-2.

Orbital MALT lymphoma in a patient with Graves' ophthalmopathy: a unique observation.

A 57-year-old woman with a six-year history of Graves' Disease with ophthalmopathy developed unilateral periorbital swelling. CT scan suggested a lacrimal mass. Biopsy revealed MALT lymphoma. Evaluation for other sites of lymphoma revealed no other evidence of disease. She was treated with radiation therapy only with complete disappearance of disease. This is the first known case of MALT lymphoma arising in Graves' ophthalmopathy.

Phase II trial of subcutaneous interleukin-2, subcutaneous interferon-alpha, 5-fluorouracil and cis-retinoic acid in the treatment of renal cell carcinoma: final results of cancer biotherapy research group 94-10.

BACKGROUND: The treatment of metastatic renal cell cancer remains unsatisfactory despite encouraging results with biotherapy. Pilot studies from other investigators have suggested that combining cis-retinoic acid and 5-fluorouracil (5FU) with interleukin-2 (IL-2) and interferon-alpha (IFN) may improve outcomes for such patients. METHODS: Eligible patients had metastatic renal cell cancer, were in good medical condition, and had not been treated previously with more than two of the study agents. A 56-day treatment cycle consisted of: interferon-alpha 2a 3.0 mu/m2 s.c. Monday, Wednesday, and Friday weeks 1-8, interleukin-2 11 mu/m2 s.c. Tuesday, Thursday and Saturday of weeks 1-4, cis-retinoic acid 1 mg/kg p.o. daily weeks 1-8, and 5-FU 750 mg/m2 i.v. weekly during weeks 5-8. Patients were evaluated for tumor response every 8 weeks, and in the absence of tumor progression, patients could receive treatment for up to one year. Survival was determined from the first date of treatment. RESULTS: The 58 renal cell carcinoma patients included 41 men and 17 women, with a median age of 57 years with a range of 28-85 who were enrolled between October 1994 and July 1997. Thirty-seven percent were asymptomatic when treatment was initiated. Sites of disease at study entry included 62% lung, 34% bone, 31% lymph node, 22% kidney, 16% liver and 10% adrenal. There were only three patients with significant tumor responses (one complete, two partial) for a response rate of 5% (0-11% 95% CI) based on intent-to-treat analysis, and 6% (0-12%, 95% CI) for the 53 patients who were evaluable for response. The response rate among evaluable nephrectomized patients who had received no prior radiation or systemic treatment was 3/25 (12%). The median failure-free survival was 2.8 months; median overall survival was 10.9 months. The 1-year survival rate was 50% and 2-year survival rate was 33%. The most frequent toxicities were fatigue-81% (26% grade 3 or 4), nausea/vomiting-59%, and leukopenia/neutropenia 57% (16% grade 3 or 4). CONCLUSION: Despite a disappointing objective response rate, survival in these patients who were treated entirely as outpatients was similar to that seen in our earlier trials of inpatient, intermediate dose continuous infusion IL-2-based therapy.