Pilot Trial of Infusional 5-Fluorouracil, Interleukin-2, and Subcutaneous Interferon-α for Advanced Renal Cell Carcinoma

Abstract

The authors developed an outpatient, three-drug combination regimen for advanced renal cell carcinoma. Treatment was administered for 5 days each week for 4 weeks, followed by 2-week rests. Each weekly treatment consisted of 5-fluorouracil 1,750 mg/m2 continuous intravenous infusion for 24 hours followed by interleukin-2 6 mIU/m2 per day continuous intravenous infusion for 4 days, and interferon-alpha2b 6 mU/m2 subcutaneously on days 1, 2, and 5. This trial was undertaken to assess tolerability to this regimen and obtain a preliminary assessment of its effectiveness. Most patients required some dose adjustments (especially of cytokines), treatment interruptions, or both. Toxicities were as would be expected from individual drug profiles with only mild to moderate hematologic toxicities. Among 16 patients with renal cell carcinoma treated, four had major (clinical partial response) responses, one of which was demonstrated to be a pathologic clinical response after surgical resection of a residual mass. Estimated median survival time of all patients was 93 weeks. Response and survival were correlated with known clinical risk factors. Responding patients were noted to be significantly older in age (X = 61.75 years) than nonresponders (X = 48.92 years). There was no correlation between age and other clinical risk factors, treatment tolerance, or survival. The authors conclude that this three-drug regimen is a practical, tolerable, and promising regimen for further study in renal cell carcinoma.

Adjuvant treatment with interleukin-2- and interferon-alpha2a-based chemoimmunotherapy in renal cell carcinoma post tumour nephrectomy: Results of a prospectively randomised Trial of the German Cooperative Renal Carcinoma Chemoimmunotherapy Group (DGCIN)

“…The lack of sc-rIL-2/sc-rIFN-a2a/iv-5-FU-related survival benefit in the adjuvant renal carcinoma therapy was disappointing, particularly when compared to the established efficacy in metastatic renal cell carcinoma patients (Lopez-Hänninen et al, 1996;Elias et al, 1999;Atzpodien et al, 2001Atzpodien et al, , 2004.…”

A Literature Analysis of Prognostic Factors for Response and Quality of Response of Patients with Renal Cell Carcinoma to Interleukin-2-Based Therapy

“…The initial rationale for performing this literature analysis was based upon our clinical observations of increased responsiveness of older patients with RCCa to IL-2-based therapy [12]. Although there have been many excellent analyses of RCCa prognostic factors, these have generally focused upon survival rather than response [6, 7, 8, 9, 10, 11].…”

“…This is a statistical literature analysis based upon 80 publications of treatment of RCCa with IL-2 alone, in combination with other agents, or with LAK cells [12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92]. Reports were identified from citations in recent complete publications and from a Medline search through July 1999.…”

“…Reports with the following characteristics were included: (1) IL-2-protein-based treatments, (2) data pertaining specifically to RCCa, and (3) clinical details of the overall study population and/or individual patients are available. Some unpublished details from our own trial [12]were included. Treatments were classified as using LAK cells, intravenously or subcutaneously applied single agent IL-2 and IL-2 delivered by any route in combination with other agents (usually an interferon and/or chemotherapy).…”

“…Age was of special interest since we found this to be associated with response in a previous trial [12]. We focused upon those studies which provided patient-specific data of responders.…”