| Abstract: |
Purpose: Blockade of the T-cell inhibitory receptor CTL-associated antigen-4 (CTLA-4) augments and prolongs T-cell responses and is a strategy to elicit antitumor immunity. The objectives of this pilot study were to establish the pharmacokinetic and safety profile for a single dose of 3 mg/kg of the anti-CTLA-4a ntibody Ipilimumab (MDX-010, BMS-734016) and to assess if this therapy resulted in prostate-specific antigen (PSA) modulation and the development of polyclonal T-cell activation and/or clinical autoimmunity in patients with hormone-refractory prostate cancer treated with Ipilimumab. Experimental Design: Patients with metastatic hormone-refractory prostate cancer received a single 3 mg/kg i.v. dose of Ipilimumab. Serologic measures of autoimmunity were obtained, and T-cell activation was evaluated by flow cytometry. Pharmacokinetic sampling of plasma for MDX-CTLA-4, PSA measurement, and diagnostic imaging were also undertaken. Results: Fourteen patients were treated: 12 patients received a single dose of Ipilimumab, and 2 patients were re-treated with a second dose upon PSA progression. Two patients showed PSA declines of ≥50%. Treatment was well tolerated with clinical autoimmunity limited to one patient who developed grade 3 rash/pruritis requiring systemic corticosteroids. The mean ± SD Ipilimumab terminal elimination half-life was 12.5 ± 5.3 days. Conclusions: A single dose of 3 mg/kg Ipilimumab, an anti-CTLA-4 antibody, given to patients with prostate cancer is safe and does not result in significant clinical autoimmunity. PSA-modulating effects observed warrant further investigation. © 2007 American Association for Cancer Research. |
| Keywords: |
adult; clinical article; controlled study; aged; middle aged; unclassified drug; prednisone; clinical trial; constipation; drug tolerability; fatigue; diarrhea; drug safety; side effect; antineoplastic agents; cancer patient; flow cytometry; antineoplastic agent; adenocarcinoma; prostate specific antigen; cytotoxic t lymphocyte antigen 4 antibody; ipilimumab; immune system; controlled clinical trial; nausea; bone pain; antineoplastic activity; drug effect; drug resistance; drug resistance, neoplasm; diagnostic imaging; cancer therapy; monoclonal antibody; abdominal pain; arthralgia; asthenia; backache; dizziness; prostate cancer; pruritus; rash; prostate-specific antigen; prostatic neoplasms; malaise; immunology; antibodies, monoclonal; rigor; pilot study; pilot projects; ibuprofen; prostate tumor; measurement; limb pain; single drug dose; autoimmunity; antigens, cd; antineoplastic agents, hormonal; drug half life; cytotoxic t lymphocyte antigen 4; serology; leukocyte antigen; antineoplastic hormone agonists and antagonists; t lymphocyte activation; antigens, differentiation; rhinopharyngitis; differentiation antigen; diphenhydramine; cimetidine; decreased appetite; wheezing; cytotoxic t-lymphocyte antigen 4; gait disorder; heart rate; hydroxyzine; pallor
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