Pharmacokinetics of BW12C and mitomycin C, given in combination in a phase 1 study in patients with advanced gastrointestinal cancer

• Published in: Cancer chemotherapy and pharmacology Vol. 32; no. 1; p. 67
• Main Authors: Dennis, I F, Ramsay, J R, Workman, P, Bleehen, N M
• Format: Journal Article
• Language: English
• Published: Germany 01.01.1993
• Subjects: Benzaldehydes - pharmacokinetics; Benzaldehydes - pharmacology; Drug Combinations; Drug Evaluation; Gastrointestinal Neoplasms - drug therapy; Half-Life; Humans; Metabolic Clearance Rate; Mitomycin - pharmacokinetics; Neoplasm Metastasis
• ISSN: 0344-5704
• DOI: 10.1007/BF00685879

The effect of combining the oxygen-transport-modifying drug BW12C with mitomycin C was investigated in a phase 1 study of 26 patients with advanced gastrointestinal cancer. The dose of BW12C was increased from 20 mg/kg to 60 mg/kg. Dose-limiting toxicity of vomiting was experienced at doses greater than 50 mg/kg. This corresponded to whole blood levels > or = 700 micrograms/ml and to > 50% haemoglobin modification. Whole blood concentrations of BW12C and modification of the haemoglobin oxygen saturation curve were linearly dependent on dose. BW12C whole blood pharmacokinetics were best described by a one-compartment model and were clearly dose-dependent. The half-life increased from 2.1 h at a dose of 20 mg/kg to 7.2 h at a dose of 60 mg/kg. The AUC increased in a similar non-linear fashion with increasing dose. Mitomycin C was given at a fixed dose of 20 mg/m2 at the end of the BW12C infusion. Mitomycin C plasma pharmacokinetics fitted a two-compartment model, giving a mean beta half-life of 50 +/- 7 min and AUC of 1.1 +/- 0.08 micrograms/ml h, and were unaffected by the combined treatment. There was no evidence of increased mitomycin C toxicity.