Quantitative estimation of the thermal dose-modifying factor for cis-diamminedichloroplatinum (CDDP) in tumour-bearing dogs.
A statistical method for estimating clinical toxicity was used to determine a theoretical isoeffect dose-modifying factor for dogs with disseminated or refractory neoplasia treated with cis-diammine dichloroplatinum (II) plus whole-body hyperthermia or CDDP alone. CDDP was administered every 3 weeks with vigorous saline hydration to 54 dogs (CDDP alone n = 21, CDDP/WBH n = 33) that were eligible for entry into this non-randomized study. CDDP was administered during the plateau phase of WBH in dogs receiving combined therapy. Acute toxicity included myelosuppression (CDDP n = 7; CDDP/WBH n = 5), nephrotoxicity (CDDP n = 1, CDDP/WBH n = 1) and respiratory distress (CDDP/WBH n = 2). Eight dogs experienced chronic renal dysfunction as a result of CDDP (n = 2) or CDDP/WBH (n = 6). A theoretical thermal dose-modifying factor was determined for both acute and cumulative toxicity by comparing the maximum tolerated dose of each treatment group. The maximum tolerated dose (MTD) of CDDP +/- WBH was defined as that dose producing a 50% incidence of moderate acute toxicity or acute plus mild chronic toxicity as estimated from logistic regression analysis of the toxicity data. The MTD (+/- .standard error) of CDDP/WBH for acute toxicity only was 54.6 (4.3) mg/M2 and for CDDP alone the MTD was 73.6 (40) mg/M2. Thus, the isoeffect dose-modifying factor for acute toxicity was 1.35 (0.12). The MTD (SE) of CDDP/WBH for cumulative toxicity (acute plus chronic toxicity) was 46.4 (2.7) mg/M2 and for CDDP alone waas 70.0 (2.9) mg/M2. The isoeffect dose-modifying factor for total cumulative toxicity was 1.5 (0.1).(ABSTRACT TRUNCATED AT 250 WORDS)
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College of Veterinary Medicine, North Carolina State University, Raleigh 27606.
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D000818:Animals; D001853:Bone Marrow / Q000187:drug effects; D003131:Combined Modality Therapy; D004283:Dog Diseases / Q000188:drug therapy* / Q000628:therapy*; D004285:Dogs; D004361:Drug Tolerance; D005260:Female; D006979:Hyperthermia, Induced / Q000379:methods / Q000662:veterinary*; D007668:Kidney / Q000187:drug effects; D008297:Male; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy / Q000662:veterinary*; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects
D009944:Organoplatinum Compounds; C055423:didimethylsulfoxide dichloroplatinum(II)