Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer.

Abstract

We performed an escalating dose study of the combined administration of interleukin-2 (IL-2) and alpha-interferon (alpha-IFN) in 94 patients with metastatic cancer. Patients received alpha-IFN at a dose of 3 x 10(6) U/m2 in conjunction with IL-2 at doses of either 1 x 10(6) U/m2 (six patients), 3 x 10(6) U/m2 (32 patients), or 4.5 x 10(6) U/m2 (26 patients). Thirty patients received alpha-IFN at 6 x 10(6) U/m2 plus IL-2 at 4.5 x 10(6) U/m2. Patients each received cytokine as an intravenous bolus infusion every 8 hours for up to 5 consecutive days and after a 10-day rest received a second cycle of combination cytokines. Of the 91 patients evaluable for response, seven patients had a complete regression of cancer, and 18 had a partial regression. At the four increasing dose levels used in patients with renal cell cancer (35 patients) or melanoma (39 patients), objective responses were seen in 17% (of six patients), 24% (of 25 patients), 38% (of 16 patients), and 41% (of 27 patients), respectively. Of the 25 total responding patients, 16 are still responding 5 to 14 months after treatment. The toxicities associated with the combined administration of IL-2 and alpha-IFN were similar to those expected from each agent alone. There was one treatment-related death in the 94 patients treated in this study. Thus, using increasing doses of the combination of IL-2 and alpha-IFN, it appears that response rates may be related to the doses of the cytokines used, and that at the highest doses of these combination cytokines, response rates may be higher than those for either cytokine alone. A prospective randomized trial comparing the cytokine combinations with each cytokine administered alone is necessary as is the extension of this combination cytokine treatment to patients with other types of solid cancer.

Randomized phase II trial of BCDT [carmustine (BCNU), cisplatin, dacarbazine (DTIC) and tamoxifen] with or without interferon alpha (IFN-α) and interleukin (IL-2) in patients with metastatic melanoma

“…Biological therapy with combined IEN-a and IL-2 may result in synergistic interactions, with enhanced antigen presentation due to IFN-a-mediated up-regulation of class 1 MHC molecules and consequent improvement in tumour recognition by IL-2-stimulated cytotoxic T cells. In early non-randomized trials, the combination of both agents as sole therapy for metastatic melanoma appeared to be superior to either agent alone (Rosenberg et al, 1989), although this was not confirmed in a subsequent randomized phase III trial of high-dose intravenous IL-2 with or without IFN-a (Sparano et al, 1993). The addition of biological therapy with both IL-2 and IFN-a to chemotherapy may prove effective because of the lack of cross-resistance, as the mechanisms of resistance are different between these modes of therapy.…”

Lung metastasectomy following kidney tumors: outcomes and prognostic factors from a single-center experience

“…About 20% to 40% of patients develops a metastatic disease after nephrectomy (3) and lung is one of the sites most frequently affected by RCC metastases (second after liver) (4). Patients that receive no treatment for metastatic RCC (mRCC) have a 0-18% 5-year survival (5). Nonsurgical therapy for mRCC has limited efficacy, with a median overall survival (OS) reported between 26.4 and 32.0 months (6,7) for mRCC patients receiving several agents targeting angiogenesis or the mTOR pathway, in addition to traditional chemotherapeutic regimens and immunotherapy (8).…”

Thyroid dysfunction can predict response to immunotherapy with interleukin-2 and interferon-2α

“…Its main role at present is in the treatment of metastatic renal cell carcinoma and malignant melanoma, where IL-2 has been used alone and also in combination with other agents such as interferon, lymphokine-activated killer (LAK) cells or tumour-infiltrating lymphocytes (TIL). Documented response rates in renal cell carcinoma and malignant melanoma in patients treated with IL-2, or with combinations of IL-2 and one of the above agents, range from 20-40% Rosenberg et al, 1989). Treatment with IL-2 is associated with a well-documented range of side-effects (Lotze et al, 1986b;Parkinson, 1988;Lotze et al, 1986a Statistical analysis Differences in survival between groups were analysed using a log-rank test.…”