title: A phase II study of the bispecific antibody MDX-H210 (anti-HER2 x CD64) with GM-CSF in HER2+ advanced prostate cancer.
abstract: The proto-oncogene HER2 presents a novel therapeutic target. We report results in 25 patients with HER2+ advanced prostate cancer treated with the bispecific antibody MDX-H210 15 microg m(-2)by intravenous infusion plus GM-CSF 5 microg kg(-1)day(-1)by subcutaneous injection for 4 days repeated weekly for 6 weeks. Patients with stable disease or better received further cycles of treatment until disease progression or study withdrawal. 1 patient received no treatment and 4 received less than 1 cycle and are included in the toxicity analysis only. Median duration of follow up was 105+ (range 21-188) days. Toxicity was generally NCI-CTG 0-2. There were 2 grade 4 adverse events (heart failure and dyspnoea) and 1 grade 3 event (allergic reaction) resulting in discontinuation of the study medication. There were 9 further grade 3 events not resulting in trial withdrawal. There were no treatment-related deaths. 7/20 (35%) evaluable patients had a >50% PSA response of median duration 128 (range 71-184+) days. 7/12 (58%) patients with evaluable pain had improvements in pain scores. The PSA relative velocity on therapy decreased in 15/18 (83%) assessable patients compared to pre-study. GM-CSF and MDX-H210 is active in hormone refractory prostate carcinoma with acceptable toxicity; further studies are warranted.
authors.affiliation: CRC Institute for Cancer Studies, University of Birmingham, Birmingham, B15 2TA, UK.
authors.forename: N D
authors.initials: ND
authors.lastname: James
authors.forename: P J
authors.initials: PJ
authors.lastname: Atherton
authors.forename: J
authors.initials: J
authors.lastname: Jones
authors.forename: A J
authors.initials: AJ
authors.lastname: Howie
authors.forename: S
authors.initials: S
authors.lastname: Tchekmedyian
authors.forename: R T
authors.initials: RT
authors.lastname: Curnow
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000368:Aged; D018033:Antibodies, Bispecific / Q000009:adverse effects / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms / Q000628:therapy*; D000090063:Proto-Oncogene Mas; D016896:Treatment Outcome
chemical_list: D018033:Antibodies, Bispecific; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C000715470:MAS1 protein, human; C121360:MDX-H210 antibody; D000090063:Proto-Oncogene Mas; D016178:Granulocyte-Macrophage Colony-Stimulating Factor