These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Phase I and pharmacokinetic study of the novel platinum analogue CI-973 on a 5-daily dose schedule.
    Author: O'Dwyer PJ, Hudes GR, Walczak J, Schilder R, LaCreta F, Rogers B, Cohen I, Kowal C, Whitfield L, Boyd RA.
    Journal: Cancer Res; 1992 Dec 15; 52(24):6746-53. PubMed ID: 1458462.
    Abstract:
    CI-973, a platinum(II) derivative with a 2-methyl-1,4-butanediamine carrier ligand, has activity in cisplatin-resistant tumor models in vitro and in vivo. In a Phase I pharmacokinetic study, 31 patients were treated with CI-973 (24 to 50 mg/m2/day for 5 days; 28-day cycles) given i.v. over 30 min without routine antiemetic prophylaxis or hydration. Of the 29 patients evaluable for maximum tolerated dose determination, most had a performance status of 0 or 1, and most had received prior chemotherapy. Neutropenia was dose limiting at 40 and 50 mg/m2/day. Recovery from neutropenia was generally rapid with nadir counts and recovery usually occurring by Days 15 and 22, respectively. Drug-associated thrombocytopenia was uncommon and never severe, even in patients with Grade 4 neutropenia. Anemia was common, but did not appear dose related. Drug-related nausea and vomiting and changes in renal function were relatively infrequent and mild. No clinically evident ototoxicity was reported, although changes in audiograms were noted in several patients. CI-973 concentrations were measured in plasma ultrafiltrate and urine by high-pressure liquid chromatography. The harmonic mean terminal half-life was 2.0 h. The mean CI-973 renal and nonrenal clearance values were 42.3 and 37.4 ml/min/m2, respectively. The mean recovery of CI-973 in urine was 53% of the administered dose. The mean ratio of CI-973 renal clearance to creatinine clearance was 0.92. Total clearance correlated with creatinine clearance (r2 = 0.63). A relationship between toxicity, expressed as the percentage of reduction in absolute granulocyte count, and area under the CI-973 plasma concentration-time curve was found in a subgroup of "good-risk" patients. This relationship, described well by a sigmoidal Emax pharmacodynamic model, did not hold for patients with extensive prior therapy or poor performance status. A model for toxicity prediction based on dose and creatinine clearance has been derived and will be validated in future studies. The recommended Phase II dose of CI-973 is 30 mg/m2/day for 5 days.
    [Abstract] [Full Text] [Related] [New Search]