High-Dose IL-2 Associated With Improved Response in Renal Cell Carcinoma Patients

September 1, 2001

Preliminary results of a phase III trial of high-dose recombinant human interleukin-2 (IL-2, Proleu kin) demonstrated increased response rates with a longer median duration, compared to outpatient subcutaneous IL-2 in conjunction with

Preliminary results of a phase III trial of high-dose recombinant human interleukin-2 (IL-2, Proleukin) demonstrated increased response rates with a longer median duration,compared to outpatient subcutaneous IL-2 in conjunction with interferon alfa-2b(Intron A) in patients with metastatic renal cell carcinoma. The results werepresented by Michael Atkins, MD, director of the cutaneous oncology and biologictherapy programs at Beth Israel Deaconess Medical Center in Boston at the 37thannual meeting of the American Society of Clinical Oncology (ASCO).

"Metastatic renal cell carcinoma is typically difficult to treat,"said Dr. Atkins. "High-dose Proleukin continues to be the only FDA-approvedtreatment for this disease, and, according to these preliminary results, appearsto induce significantly more and higher quality responses than low-doseProleukin in combination with interferon. High-dose Proleukin remains the goldstandard for metastatic kidney cancer."

High-Dose IL-2 Shows StrongerRelative Response Rates

The randomized phase III study in 193 patients with metastatic renal cellcarcinoma was conducted by the Cytokine Working Group to determine the effect ofinpatient high-dose bolus IL-2 compared to outpatient subcutaneous IL-2 inconjunction with interferon alfa-2b. High-dose IL-2 was administeredintravenously at 600,000 IU/kg every 8 hours to 99 patients on days 1 through 5and 15 through 19 (maximum of 28 doses) every 12 weeks. Low-dose IL-2 wasadministered subcutaneously to 94 patients at 5 mIU/m² every 8 hours for 3 doseson day 1, then once daily 5 days a week for 4 weeks in conjunction withinterferon alfa-2b (subcutaneously, 5 mIU/m² three times a week for 4 weeks)every 6 weeks.

Tumor responses were assessed at weeks 6 and 12, and every 12 weeksthereafter. The patients’ ages ranged from 21 to 75 years (median age: 54years). Overall, 25% of patients had primary metastases; 19% and 32% had liverand bone metastases, respectively.

In the high-dose IL-2 group, a tumor response was seen in 25 of 99 patientstreated, or 25% (95% confidence interval: 17.1%-35%). Complete responses wereseen in 8 patients, and partial responses in 17. Among patients treated withlow-dose IL-2 in combination with interferon alfa-2b, a tumor response was seenin 12 of 94 patients, or 12% (6.8%-21.2%). Two patients achieved a completeresponse and 10 had a partial response.

The median duration of response in the patients receiving high-dose IL-2 was10 months, compared with 7 months for patients receiving low-dose IL-2 andinterferon alfa-2b.

Primary End Points Still Being Assessed

These patients have not been followed long enough to determine overallsurvival and progression-free survival (the study’s primary end points). Thesedata will be made available upon completion of the study, which was supported byChiron.

Observed toxicities were typical for these regimens, including onetreatment-related death in the high-dose bolus IL-2 group from capillary leaksyndrome.

Historically, the median survival of patients with metastatic kidney canceris 6 to 12 months. Previous studies with high-dose bolus IL-2 demonstrated a 15%response rate, with a median response duration of 54 months. Some patients havesurvived beyond 10 years at last analysis