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CONTINOUS INFUSION IL-2
Cancer J Sci Am 1997 Dec;3 Suppl 1:S85-91
Metastatic renal cell carcinoma: long-term survival after therapy with high-dose continuous-infusion interleukin-2.
Gold PJ, Thompson JA, Markowitz DR, Neumann S, Fefer A.
University of Washington School of Medicine, Seattle 98195-6043, USA.
PURPOSE: This article undertakes to define the response rate, long-term survival, and toxicity in patients with metastatic renal cell carcinoma (MRCC) treated with high-dose continuous intravenous infusion (CIV) recombinant interleukin-2 (rIL-2) with or without lymphokine-activated killer (LAK) cells. PATIENTS AND METHODS: One hundred twenty-three consecutive patients received CIV rIL-2 (18-22 MIU/m2/day on days 1-5, and 6-8 MIU/m2/day on days 10-19) on one of five sequential protocols at the University of Washington between 1988 and 1995. The first 76 patients received LAK cells. The median age was 55 years (range, 32-76 years), and 71% had undergone prior nephrectomy. RESULTS: Nine patients achieved a complete response (7.3%) and 14 patients achieved a partial response (11.4%) for an overall response rate of 19% (95% confidence interval, 12%-26%). The median survival was 19 months, and the 5-year survival was 20%. Seven of nine complete responders (78%) remain in continuing complete response at 43+ to 109+ months. Intensive care unit and vasopressor support were required in 42% and 23% of patients, respectively, who received rIL-2 + LAK cells, and in 18% and 4% of those who received rIL-2 alone. There was one treatment-related death. CONCLUSION: We report the largest single-institution experience and the longest survival for patients with MRCC treated with CIV rIL-2. The administration of rIL-2 by CIV is associated with less frequent intensive care unit and vasopressor support than with high-dose intravenous bolus regimens, and hence may enhance the therapeutic index in patients with MRCC
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HIGH-DOSE IL-2
IL-2 600,000 0r 720,000 IU/Kg administered by 15 minute IV infusion Q8 hours for as many as 14 consecutive doses during 5 days as clinically tolerated.
Follow by a second identical cycle after an approximate 10-day rest with courses repeated Q 6-12 weeks.
CR 7% PR 20% with median duration of response 54 months (3-107+)
REF:
Cancer J Sci Amer 3:S70, 1997.
J Clin Oncol; 13(3):688-96 1995
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IL-2 Subcutaneous (outpatient)
IL2 given QD, 5 days per week X 6 weeks.
During the first 5-day cycle: 18 x 10(6) IU given QD; in the following cycles, the doses in the first 2 days are reduced to 9 x 10(6) IU.
After a 3-week rest period, treatment is repeated in patients who had a response or stable disease (SD). Prophylaxis: Acetaminophen 250 to 500 mg given PO Q4-6 hours.
REF: J Clin Oncol; 10(7):1119-23 1992.
After 6 weeks, 26 patients were assessable for response. 2 patients (8%) had a CR, 4 (15%) had a PR, & 13 (50%) had SD. A second cycle of 6 weeks was given to 19 patients; 1 patient with a PR and 6 with SD showed progression. Duration of the CR was 17+ & 19+ months, & length of the PR was 2, 8, 11, and 11+ months. The median survival of the patients who were nonresponders & responders was 10 and 20+ months, respectively, & for all patients was 13 months. One patient died of MI & brain stem ischemia. Systemic side effects in the other patients were tolerated & accepted, & included transient inflammation & local induration at the injection sites, fever and chills, and nausea.
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IL2+INF+5FU Regimen (Atzpodien et al)
rIL-2 20 X 10(6) IU/m2 SC TIW weeks 1,4. 5X 10(6) IU/m2 SC TIW weeks 2,3,5,6
IFN-a 6 x 10(6) U/m2 SC Q week 1,4 & TIW weeks 2,3,5,6
5FU 750 mg/m2 IV bolus Q week 4,5,6,7,8
REF: Proc ASCO 1994:13:247 (Absr 773)
Important Note: This regimen remains contraversial. Some studies have shown RR as high as 47% and some have not been able to reproduce results. Expect high toxicity.
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Thalidomide
Start at 200 mg PO QD
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Non-myeloablative approach
NEJM 343(11): 750-758, 2000.
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Interferon vs Interferon + Thalidomide
ECOG study- active
IFN 1 MU BID
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