A multi-institutional phase II study of BMS-182248-01 (BR96-doxorubicin conjugate) administered every 21 days in patients with advanced gastric adenocarcinoma.
OBJECTIVE
High levels (> 200,000 molecules per carcinoma cell) of the LewisY antigen are expressed on the surface of most (> 75%) gastric carcinomas. The BMS-182248-01 is a chimeric variant of anti-LewisY monoclonal antibody that is conjugated with doxorubicin. In a phase I study, BMS-182248-01 resulted in a partial response in a patient with gastric carcinoma. We, therefore, conducted a multi-institutional phase II study of BMS-182248-01 in patients with advanced gastric carcinoma.


METHODS
Only patients with evidence of LewisY antigen by immunohistochemical method on their gastric carcinoma were treated. Patients with unresectable gastric adenocarcinoma were eligible. Patients had to have adequate liver, renal, and marrow functions. Written consent was obtained from all patients. All patients were hospitalized. BMS-182248-01 was administered at the starting dose of 700 mg/m2 i.v. over 24 hours on day 1 every 3 weeks.


RESULTS
Fifteen patients were enrolled. There were 10 men and 5 women. The median age at enrollment was 56 years, with ages ranging from 34 to 80 years. No objective responses were observed. Five patients had disease stabilization. The remaining 10 patients progressed on study. Rapidly reversible gastrointestinal toxicity, primarily nausea and emesis, was predominant. There was no neutropenia, thrombocytopenia, or cardiomyopathy.


CONCLUSIONS
Although BMS-182248-01 represents a novel approach of monoclonal antibody conjugated with an active chemotherapy agent, delivered intracellularly, it was ineffective in patients with gastric carcinoma whose tumors carried LewisY antigen.
Ajani
J A
JA
Department of Gastrointestinal Oncology and Digestive Diseases, University of Texas M.D. Anderson Cancer Center, Houston, USA.
Kelsen
D P
DP
Haller
D
D
Hargraves
K
K
Healey
D
D
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007167:Immunotherapy; D016256:Lewis X Antigen / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D009362:Neoplasm Metastasis; D012449:Safety; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016896:Treatment Outcome; D014839:Vomiting / Q000139:chemically induced
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; C092612:BR96-doxorubicin immunoconjugate; D016256:Lewis X Antigen; D004317:Doxorubicin