Abstract |
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.
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Authors | I F Dennis, J R Ramsay, P Workman, N M Bleehen |
Journal | Cancer chemotherapy and pharmacology
(Cancer Chemother Pharmacol)
Vol. 32
Issue 1
Pg. 67-72
( 1993)
ISSN: 0344-5704 [Print] Germany |
PMID | 8462126
(Publication Type: Clinical Trial, Journal Article)
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Chemical References |
- Benzaldehydes
- Drug Combinations
- Mitomycin
- 5-(2-formyl-3-hydroxyphenoxy)pentanoic acid
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Topics |
- Benzaldehydes
(pharmacokinetics, pharmacology)
- Drug Combinations
- Drug Evaluation
- Gastrointestinal Neoplasms
(drug therapy)
- Half-Life
- Humans
- Metabolic Clearance Rate
- Mitomycin
(pharmacokinetics)
- Neoplasm Metastasis
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