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 interferon alfa-2b
(Intron A) in patients with metastatic renal cell carcinoma. The results were
presented by Michael Atkins, MD, director of the cutaneous oncology and biologic
therapy programs at Beth Israel Deaconess Medical Center in Boston at the 37th
annual 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-approved
treatment for this disease, and, according to these preliminary results, appears
to induce significantly more and higher quality responses than low-dose
Proleukin in combination with interferon. High-dose Proleukin remains the gold
standard for metastatic kidney cancer."
High-Dose IL-2 Shows Stronger Relative Response Rates
The randomized phase III study in 193 patients with metastatic renal cell
carcinoma was conducted by the Cytokine Working Group to determine the effect of
inpatient high-dose bolus IL-2 compared to outpatient subcutaneous IL-2 in
conjunction with interferon alfa-2b. High-dose IL-2 was administered
intravenously at 600,000 IU/kg every 8 hours to 99 patients on days 1 through 5
and 15 through 19 (maximum of 28 doses) every 12 weeks. Low-dose IL-2 was
administered subcutaneously to 94 patients at 5 mIU/m² every 8 hours for 3 doses
on day 1, then once daily 5 days a week for 4 weeks in conjunction with
interferon 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 weeks
thereafter. The patients’ ages ranged from 21 to 75 years (median age: 54
years). Overall, 25% of patients had primary metastases; 19% and 32% had liver
and bone metastases, respectively.
In the high-dose IL-2 group, a tumor response was seen in 25 of 99 patients
treated, or 25% (95% confidence interval: 17.1%-35%). Complete responses were
seen in 8 patients, and partial responses in 17. Among patients treated with
low-dose IL-2 in combination with interferon alfa-2b, a tumor response was seen
in 12 of 94 patients, or 12% (6.8%-21.2%). Two patients achieved a complete
response and 10 had a partial response.
The median duration of response in the patients receiving high-dose IL-2 was
10 months, compared with 7 months for patients receiving low-dose IL-2 and