Phase I study of BW12C in combination with mitomycin C in patients with advanced gastrointestinal cancer.
The effect of combining the oxyhemoglobin-modifying drug BW12C with mitomycin C was investigated in a Phase I study of 18 patients with advanced gastrointestinal cancer. The dose of BW12C was increased from 20 mg/kg to 50 mg/kg to modify the hemoglobin-oxygen saturation curve by up to 48%. The period of maximum modification was then prolonged for up to 3 hr by a maintenance infusion of 4-6 mg/kg/hr. Pharmacokinetics of BW12C and mitomycin C were performed in all patients. Peak levels of BW12C increased from 139 micrograms/ml to 378 micrograms/ml. Plasma half life was independent of dose, with an average of 3.3 hr. BW12C was well tolerated with no severe side effects. Three patients had objective tumour responses.
Ramsay
J R
JR
Medical Research Council Unit, Cambridge, UK.
Bleehen
N M
NM
Dennis
I
I
Workman
P
P
Ward
R
R
Falk
S J
SJ
Bedford
P
P
Wootton
R
R
Nethersell
A B
AB
D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001547:Benzaldehydes / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004341:Drug Evaluation; D005770:Gastrointestinal Neoplasms / Q000188:drug therapy*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010100:Oxygen / Q000097:blood
D001547:Benzaldehydes; D006454:Hemoglobins; D016685:Mitomycin; C039599:5-(2-formyl-3-hydroxyphenoxy)pentanoic acid; D010100:Oxygen