Treatment of Metastatic Renal Cell Carcinoma with High-Dose Bolus IL-2 in a Non-Intensive Care Unit

ABSTRACT & COMMENTARY

Synopsis: Despite its well-recognized limitations, high-dose IL-2 remains a consideration for otherwise healthy patients with metastatic renal cell carcinoma who are minimally symptomatic. One limitation to making this treatment more available has been timely access to ICU beds. This report outlines a 7-year experience in giving this treatment in a non-ICU setting. However, regardless of the setting, a well-trained, experienced, and motivated staff is critical if the treatment is to be given safely.

Source: Gitlitz BJ, et al. Cancer J. 2001;7:112-121.

While low-dose subcutaneous il-2 is fre-quently used for the treatment of metastatic renal cell carcinoma (mRCC), high-dose IL-2, as approved by the FDA, remains the standard by which other therapies are judged. However, its toxicity and the need for intensive care unit (ICU) support have limited widespread use of this regimen. Patients with poor performance status or impaired cardiopulmonary function are not candidates due to the high rate of treatment-related complications and mortality. Implementation of the treatment is also limited by access to ICU beds. Gitlitz and colleagues at UCLA report the results of 124 patients treated from July 1992 to October 1999 with the standard high-dose IL-2 regimen (each course consisted of 2 cycles of 600,000 IU/kg q 8 hours IV bolus over 15 minutes for a maximum of 14 doses over a 5-day period separated by 10-14 days). Patients who tolerated the treatment regimen and did not develop progressive disease were treated again 4-6 weeks later with a second course. If reversible grade 3 toxicity occurred, injections were withheld until the toxicity decreased to grade 0 or 1. If grade 4 nonhematologic toxicity occurred, no further injections were administered for that cycle. Typical toxicities included fever, rash, and pruritus, nausea and vomiting, diarrhea, electrolyte imbalances, and hypotension. Management included standard medications used for these symptoms, electrolyte replacement therapies, and pressors. Standard response criteria were used to assess efficacy.

Of the 124 patients, 53 (42.7%) had a performance status of 0. The remaining 57.3% had a performance status of 1. All had normal cardiac and pulmonary function. Approximately three-fourths of the patients had undergone a nephrectomy, and almost all had not previously received treatment for metastatic disease. The number of IL-2 injections administered in the first course of treatment was comparable to that of regimens using ICU support that have been reported in the literature (median of 19 doses; range, 5-28).1 Approximately half of the patients received a second course of treatment and received a median of 13 doses (range, 2-20). Patients who responded did not, on average, receive more IL-2 than those who did not have an objective tumor regression. The complete and partial antitumor response rates (5.6% and 8.9%) and median response duration (18 months) were also comparable to those reported in the literature for high-dose IL-2.1,2 The response rates for patients with performance status of 0 and 1 were 17% and 13%, respectively. Three of 7 patients with complete remissions, and 6 of 11 patients with partial responses had not yet progressed at the time of the analysis.

Almost half of the patients developed hypotension requiring pressor support. Approximately one-fifth of the patients developed an arrhythmia, but only 2 patients (1.6%) had ventricular tachycardia or fibrillation. Hallucinations or other significant neurotoxicity occurred in 35% of patients. Elevations of the serum creatinine and bilirubin and thrombocytopenia were common but easily managed. However, despite the presence of a well-trained and experienced staff, 7% of patients required transfer to an ICU at some point in their treatment. There were no treatment-related deaths.

COMMENT BY MICHAEL J. HAWKINS, MD

The use of high-dose IL-2 remains problematic. While treatment-related mortality has decreased with greater experience, effective management of side effects to maximize the amount of IL-2 administered remains a daunting task. Patients must be carefully selected based upon cancer-related performance status and comorbid conditions. With experience, however, personnel who are well trained and capable of providing blood pressure support as needed can administer this aggressive regimen largely outside of an ICU. Nonetheless, most patients will not benefit from this treatment while experiencing severe, but reversible, morbidity. However, despite these sobering considerations, some patients will achieve durable and at times complete regressions of their metastatic disease. Since similar results have not yet been reported for other therapies in mRCC, high-dose IL-2 remains a consideration for otherwise healthy patients who are minimally symptomatic from their cancer. This report addresses 1 resource limitation to potentially make this treatment more readily available. Regardless of the venue in which high-dose IL-2 is administered, the importance of a dedicated and experienced staff cannot be underestimated.

References

1. Fyfe G, et al. J Clin Oncol. 1995;13:688-696.

2. Fisher RI, et al. Cancer J Sci Am. 2000;6(Suppl 1): S55-S57.