Publications (2)15.48 Total impact
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Article: A phase 2 study of rituximab in combination with recombinant interleukin-2 for rituximab-refractory indolent non-Hodgkin's lymphoma.
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ABSTRACT: The incidence of non-Hodgkin's lymphoma (NHL), the fifth most common malignancy in the United States, has increased over 70% in the last 30 years. Fifty percent to 75% of patients with low-grade or follicular NHL respond to rituximab therapy. However, responses are generally of limited duration, and complete responses are rare. Preclinical work suggests that human recombinant interleukin-2 (rIL-2; aldesleukin, Proleukin) enhances rituximab efficacy. Antibody-dependent cellular cytotoxicity (ADCC) is an important mechanism of action of rituximab. rIL-2 induces expansion and activation of Fc receptor (FcR)-bearing cells, thereby enhancing ADCC. Therefore, a large, multicenter phase 2 trial to assess the effects of rIL-2 on rituximab therapy in patients with rituxumab-refractory low-grade NHL was conducted. The combination of rituximab and rIL-2 was studied in 57 patients with rituximab-refractory low-grade NHL (i.e., patients must have received a single-agent course of rituximab and showed no tumor response, or had a response lasting <6 months). I.V. rituximab was given at 375 mg/m(2) (weeks 1-4). S.C. rIL-2 was given thrice a week at 14 MIU (weeks 2-5) and at 10 MIU (weeks 6-9). Rituximab plus rIL-2 combination therapy was safe and generally well tolerated, but responses were low. Fifty-seven patients were enrolled with 54 evaluable for response; however, only five responses (one complete and four partial) were observed. Correlative data indicate that rIL-2 expanded FcR-bearing cells and enhanced ADCC. However, other factors, such as FcgammaR polymorphisms in patients refractory to single-agent rituxumab and heterogeneous tumor biology, may have influenced the lack of clinical efficacy seen with this combination therapy. rIL-2 expands FcR-bearing cellular subsets in vivo and enhances in vitro ADCC of rituxumab. However, these findings do not directly translate into meaningful clinical benefit for patients with rituxumab-refractory NHL.Clinical Cancer Research 01/2007; 12(23):7046-53. · 7.74 Impact Factor -
Article: Maintenance biotherapy for metastatic melanoma with interleukin-2 and granulocyte macrophage-colony stimulating factor improves survival for patients responding to induction concurrent biochemotherapy.
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ABSTRACT: A prospective Phase II study of a novel maintenance biotherapy regimen after induction biochemotherapy was conducted in patients with metastatic melanoma in efforts to maintain responses and improve survival. Thirty-three patients with poor prognosis metastatic melanoma who achieved a partial response (PR) or stable disease (SD) to induction concurrent biochemotherapy were treated with chronic low-dose interleukin (IL)-2 and granulocyte macrophage-colony stimulating factor, and intermittent pulses of intermediate/high-dose decrescendo IL-2 over a 12-month period. The outcome of these patients was compared with a control group of patients at our institution who were treated recently with induction biochemotherapy and achieved a PR or SD. Five patients (15%) achieved a complete response, and 4 patients (12%) maintained SD for at least 6 months on maintenance biotherapy. The median progression-free survival (PFS) and overall survival (OS) were 8.1 months and 18.5 months, respectively, compared with historical controls, which were PFS 5.9 months (P = 0.0015) and OS 9.3 months (P = 0.0004). Administration of maintenance biotherapy was a significant predictor of PFS (P = 0.0008) and OS (P = 0.0001) in multivariate and matched-pair analyses (P = 0.002). The maintenance biotherapy regimen was well tolerated with no dose-limiting acute or cumulative toxicities. In this single institution study, maintenance biotherapy with IL-2 and granulocyte macrophage colony-stimulating factor in patients achieving PR or SD to induction biochemotherapy improved PFS and OS compared with historical controls. A larger multicenter Phase II trial has been initiated in an effort to confirm these results.Clinical Cancer Research 10/2002; 8(9):2775-81. · 7.74 Impact Factor
