Phase I evaluation and pharmacokinetic study of weekly iv thymidine and 5-FU in patients with advanced colorectal carcinoma Journal Article


Authors: Lynch, G.; Kemeny, N.; Chun, H.; Martin, D.; Young, C.
Article Title: Phase I evaluation and pharmacokinetic study of weekly iv thymidine and 5-FU in patients with advanced colorectal carcinoma
Abstract: A phase I study of weekly iv thymidine (TdR) and 5-FU was carried out in patients with advanced colorectal carcinoma using two dosage schedules. Schedule 1 employed a 3-hour infusion of TdR (6-8 g/m2/hour) followed immediately by a bolus of 5-FU (100-200 mg/m2). Schedule 2 used a slightly larger dose of TdR (18 g/m2/hour for 1.5 hours), with 5-FU given 30 minutes after the TdR infusion was started. Myelosuppression was observed erratically at the higher doses of 5-FU. Diarrhea and severe fatigue were seen frequently with Schedule 1. CNS side effects were the dose-limiting effects for both schedules. For long-term use the maximally tolerated 5-FU doses were 100 mg/m2/week for Schedule 1 and 175 mg/m2/week for Schedule 2. In pharmacokinetic studies in five patients, both schedules produced prolonged plasma beta-half-lives of 5-FU (96-189 minutes). Extensive formation of floxuridine was seen with both schedules. It appears likely that CNS toxic effects are characteristic of TdR-containing 5-FU regimens and would limit the therapeutic potential of this approach.
Keywords: adult; cancer chemotherapy; aged; middle aged; major clinical study; fatigue; fluorouracil; cancer combination chemotherapy; diarrhea; drug efficacy; neurotoxicity; mucosa inflammation; nausea; vomiting; antineoplastic combined chemotherapy protocols; drug administration schedule; colonic neoplasms; central nervous system; colorectal carcinoma; gastrointestinal toxicity; kinetics; neoplasm metastasis; drug blood level; phase 1 clinical trial; drug half life; drug therapy; toxicity; rectal neoplasms; ataxia; adverse drug reaction; therapy; infusions, parenteral; half-life; intravenous drug administration; thymidine; nervous system; vertigo; bone marrow depression; drug evaluation; intoxication; large intestine; cancer; humans; human; priority journal; blood and hemopoietic system
Journal Title: Cancer Treatment Reports
Volume: 69
Issue: 2
ISSN: 0361-5960
Publisher: National Cancer Institute  
Date Published: 1985-02-01
Start Page: 179
End Page: 184
Language: English
PUBMED: 3971391
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 26 October 2021 -- Source: Scopus
Citation Impact
MSK Authors
  1. Nancy Kemeny
    544 Kemeny
  2. Charles W Young
    82 Young