Phase IB trial for malignant melanoma using R24 monoclonal antibody, interleukin-2/α-interferon |
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Authors: | R Katherine Alpaugh PhD Margaret von Mehren Irma Palazzo Michael B Atkins Joseph A Sparano Lynn Schuchter Louis M Weiner Janice P Dutcher |
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Institution: | (1) Fox Chase Cancer Center, 7701 Burholme Avenue, 19111 Philadelphia, PA, USA;(2) Jeanes Hospital, Philadelphia;(3) Tufts University/New England Medical Center, Boston, MA;(4) Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, New York;(5) University of Pennsylvania, Philadelphia, MA, USA |
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Abstract: | The inflammatory tumor lymphocytic infiltrates and spontaneous tumor regressions seen in patients with metastatic malignant
melanomas suggest a cellular immune involvement. Enhancement of such responses has been the goal of R24 (GD3 ganglioside-specific)
monoclonal antibody trials, alone and in combination with other agents. This study reports the results of 21 patients treated
in a phase IB trial employing R24 (0, 5, 25, 50 mg/m2) administered by continuous i.v. infusion on days 1–5 followed by 3mU each of interleukin-2 (IL-2) and alpha interferon (α-IFN) given subcutaneously on days 8–12, 15–19 and 22–26. R24-related
toxicities occurred pre-dominantly at the 25 and 50 mg/m2 doses. One patient (50 mg/m2 R24) exhibited a dose-limiting Grade 4 anaphylaxis. Cytokine-related toxicities required IL-2/α-IFN dose reduction in two
patients and early termination of treatment in five additional patients. Nine of 20 baseline biopsies showed chronic inflammation;
six with lymphocytic tumor infiltration and three where inflammation was confined to the perivascular/ peritumoral spaces.
No day 8 or 29 biopsies in the R24-treated groups demonstrated treatment-induced tumor lymphocytic infiltrates. However, one
patient randomized to no R24 treatment, showed a significant inflammatory tumor lymphocytic infiltration at days 8 and 29.
Eighteen of 21 treated patients were evaluable for response. One (5%) patient receiving IL-2/α-IFN alone had stable disease
lasting 1.5 years. Five (28%) R24, IL-2/α-IFN-treated patients had stable disease ranging from 6 to 32 weeks, with one patient
remaining alive 2.5 years post-treatment. Although this combined treatment program was generally well tolerated, no objective
responses were seen and significant R24-induced tumor lymphocytic infiltrates were not demonstrated. |
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Keywords: | monoclonal antibody R24 IL-2 α -IFN melanoma |
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