ISSN:
1569-8041
Keywords:
antibody
;
calicheamicin
;
CMB-401
;
immunotherap/kwd〉
;
ovarian cancer
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Purpose:We have performed a phase I study of the cytotoxicimmunoconjugate CMB-401 in women with epithelial ovarian cancer (EOC). CMB-401is a directed chemotherapy that comprises a genetically engineered humanantibody against polymorphic epithelial mucin, to which is attached covalentlytwo to three molecules, on average, of the cytotoxic antibiotic calicheamicin.The primary objectives of this two-centre study were to identify end-organtoxicities and to establish the maximum tolerated dose (MTD). Patients and methods:Thirty-four patients aged 37–75 yearswith progressive EOC not amenable to platinum/standard therapy, and withsatisfactory WHO performance status (0–2) were recruited. Patients hadreceived a mean of 3.2 previous chemotherapeutic regimens with a medianinterval since last chemotherapy of 182 days (range 34–1217). Patientsreceived up to four cycles of a dual infusion of 35 mg/m2 hCTMO1`pre-dose' followed by doses of CMB-401 which were increased for each cohort– a regimen which minimises drug uptake in normal tissues whilstenhancing delivery to the ovarian tumour. CMB-401 dosing commenced at 2mg/m2 and progressed via seven cohorts to 16 mg/m2. Results:CMB-401 was generally well tolerated. However, transientfever and emesis occurred, necessitating routine prophylaxis, and increasinglysignificant malaise was reported as the dose increased. WHO grade 3–4toxicities, irrespective of causality, included: anaemia 21%,granulocytopenia 9%, thrombocytopenia 9%, liver transaminases3%, sepsis 3%, haemorrhage 6%, nausea/vomiting76%; pulmonary 6%, and conscious state/somnolence 6%. TheMTD was reached at 16 mg/m2. During the study four patients had agreater than 50% reduction in CA125, and three patients hadradiological evidence of reduction in tumour bulk. Conclusions:CMB-401 appears to have an acceptable toxicityprofile with demonstrable activity against EOC.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1023/A:1008349300781
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