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 |
