Topics:

High-Dose Interleukin-2 in Metastatic Disease: Renal Cell Carcinoma and Melanoma

High-Dose Interleukin-2 in Metastatic Disease: Renal Cell Carcinoma and Melanoma

Despite significant advances in the treatment of a
variety of malignancies, highly effective therapies for most patients with
metastatic renal cell carcinoma or metastatic melanoma are rare. Traditional
oncologic treatment methods, such as chemotherapy, surgery, and radiation
therapy, are marginally effective in these diseases, except in special
circumstances.[1-3] Systemic immunotherapy with cytokines, such as interferon
alfa (IFN-a, Intron A, Roferon-A) and interleukin 2
(IL-2, Proleukin), produces the highest response rates (10% to 27% [renal cell
carcinoma] and 15% to 20% [melanoma]), but the search for more effective
therapies continues.[2,4,5]

Efficacy of High-Dose IL-2

Since the first National Cancer Institute reports of the effectiveness of
high-dose IL-2 (administered as an IV bolus) and lymphokine-activated killer (LAK)
cells in patients with advanced malignancies, research has focused on
establishing effective IL-2-based therapies, primarily for patients with
metastatic renal cell carcinoma and metastatic melanoma.[6,7] The addition of
LAK cells to high-dose IL-2 therapy was eventually abandoned, but high-dose IL-2
therapy remains the treatment of choice for these two advanced malignancies,
producing overall response rates of approximately 15%.[1,7,8]

The use of high-dose IL-2 therapy for metastatic renal cell carcinoma and
metastatic melanoma, however, is associated with significant toxicity, including
hypotension requiring vasopressor support, oliguria, pulmonary congestion,
arrhythmias, and neurologic toxicity. To reduce toxicity and maintain or improve
efficacy, researchers have investigated several other regimens, such as those
using lower IL-2 doses or alternative methods of administration (eg, continuous
IV infusion, subcutaneous). Unfortunately, none of these alternative regimens
have proven superior to high-dose IL-2 therapy in patients with metastatic renal
cell carcinoma or metastatic melanoma.[2,4] Additionally, combining IL-2 with
IFN-a, chemotherapy agents, or both has not
significantly improved the outcome in patients with metastatic renal cell
carcinoma.[7] In metastatic melanoma patients, the use of IL-2-based
biochemotherapy has been quite promising, producing overall response rates as
high as 64%, but recent preliminary data from a large, randomized, multicenter
study comparing biochemotherapy with chemotherapy alone suggest that
biochemotherapy is not significantly better than chemotherapy (M.B. Atkins, oral
communication, June 2002).[2] Therefore, high-dose IL-2 therapy is likely to
remain one of the most logical therapies for patients with metastatic renal cell
carcinoma and metastatic melanoma.

Review of Clinical Trials

The first article in this supplement provides
a comprehensive review of the available results of clinical trials evaluating
IL-2-based therapy for metastatic renal cell carcinoma and melanoma.

Managing Toxicities

The second article focuses on the safe administration
of high-dose IL-2 and appropriate techniques for managing toxicities. My coauthors,
Rowena Schwartz, PharmD, BCOP, and Lori Stover, RN, BSN, are both experienced
health-care practitioners at the University of Pittsburgh Cancer Institute,
which treats more than 400 new melanoma patients each year and is a cancer center
with many years of experience in the administration of high-dose IL-2.

Pages

 
Loading comments...

By clicking Accept, you agree to become a member of the UBM Medica Community.