A phase 1, multicenter, open-label study of the safety of two dose levels of a human monoclonal antibody to human α(v) integrins, intetumumab, in combination with docetaxel and prednisone in patients with castrate-resistant metastatic prostate cancer.
OBJECTIVE
We evaluated the safety and efficacy of intetumumab in combination with docetaxel in patients with castrate-resistant metastatic prostate cancer. Patients and methods In this phase 1, open-label, multicenter, nonrandomized study, 75 mg/m² docetaxel was administered on Day 1 of each of nine 21-day treatment cycles and intetumumab 5 or 10 mg/kg was administered on Days 1, 8, and 15 of Cycles 2 and 3 and on Day 1 of all subsequent cycles. The primary endpoint was the incidence of dose-limiting toxicities (DLTs) during Cycles 2 and 3. Secondary endpoints included serum prostate-specific antigen (PSA) response and objective response based on Response Evaluation Criteria in Solid Tumors (RECIST).


RESULTS
Ten patients were treated (5 mg/kg n = 3, 10 mg/kg n = 7). No DLTs occurred. Most treatment-emergent adverse events (TEAEs) occurred in the 10-mg/kg intetumumab group. Common TEAEs were neutropenia (10 mg/kg n = 6) and nausea (5 mg/kg n = 1, 10 mg/kg n = 5). Four 10-mg/kg-treated patients reported serious TEAEs; of these, only febrile neutropenia was considered probably intetumumab-related. In the 10-mg/kg group, four patients had a serum PSA response (two of whom responded within 3 months of treatment), one patient demonstrated partial tumor response for 11 weeks, and none had progressive disease at Cycle 9. No PSA or tumor response was observed in the 5-mg/kg group.


CONCLUSIONS
Intetumumab was generally safe and well tolerated in combination with docetaxel, with a higher incidence of TEAEs in the 10 mg/kg dose cohort. The efficacy of 10 mg/kg intetumumab in combination with docetaxel appears to warrant further study.
Chu
Franklin M
FM
San Bernardino Urological Associates Medical Group, San Bernardino, CA, USA. FMCSBU@aol.com
Picus
Joel
J
Fracasso
Paula M
PM
Dreicer
Robert
R
Lang
Zhihui
Z
Foster
Brenda
B
D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D002369:Castration; D000077143:Docetaxel; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D039564:Integrin alphaV / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D011241:Prednisone / Q000008:administration & dosage / Q000627:therapeutic use*; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D039564:Integrin alphaV; D043823:Taxoids; D000077143:Docetaxel; C486839:intetumumab; D011241:Prednisone