The role of drug sequence in therapeutic selectivity of the combination of 5-fluorouracil and cis-platin

S Palmeri; F Trave; O Russello; Y M Rustum

doi:10.1089/sct.1989.5.169

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The role of drug sequence in therapeutic selectivity of the combination of 5-fluorouracil and cis-platin

Journal article

Peer reviewed

The role of drug sequence in therapeutic selectivity of the combination of 5-fluorouracil and cis-platin

S Palmeri, F Trave, O Russello and Y M Rustum

Selective cancer therapeutics, Vol.5(4), pp.169-177

1989

DOI: 10.1089/sct.1989.5.169

PMID: 2623382

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Abstract

The therapeutic efficacy of 5-fluorouracil (FUra) and cis-dichlorodiamine-platinum (cis-DDP) in mice bearing transplantable leukemia and solid tumors was evaluated using different sequences of combination of these agents. The optimal sequence was cis-DDP administered 24 h after FUra. The administration of FUra at its maximally tolerated dose (MTD) followed 24 h later by low doses of cis-DDP yielded less toxicity and higher response rate against L1210 and colon 26 than the administration of these two agents in the opposite sequence or concurrently at the MTD. The sequence of administration of these two agents was not therapeutically important when the antitumor activity was evaluated against mice bearing lymphoma P388. These results indicate that the importance of sequencing of FUra and cis-DDP varies among different tumors. The biochemical basis for the therapeutic importance of sequencing in treatments with cis-DDP and FUra was investigated in mice bearing leukemia L1210 cells. While cis-DDP has no significant effects on the activity of thymidylate synthase (dTMP-S), the target enzyme for FUra action, recovery of dTMP-S inhibition following pretreatment with FUra was significantly delayed when cis-DDP was administered 12-24 h after the initial dose of FUra.

Animals

Antineoplastic Combined Chemotherapy Protocols - therapeutic use

Cisplatin - administration & dosage

Cisplatin - therapeutic use

Colonic Neoplasms - drug therapy

Dose-Response Relationship, Drug

Drug Administration Schedule

Fluorouracil - administration & dosage

Fluorouracil - therapeutic use

Leukemia L1210 - drug therapy

Lymphoma - drug therapy

Mice

Mice, Inbred DBA

Thymidylate Synthase - metabolism

Tumor Cells, Cultured - drug effects

Details

Title: Subtitle: The role of drug sequence in therapeutic selectivity of the combination of 5-fluorouracil and cis-platin
Creators: S Palmeri - University of Palermo
F Trave
O Russello
Y M Rustum
Resource Type: Journal article
Publication Details: Selective cancer therapeutics, Vol.5(4), pp.169-177
DOI: 10.1089/sct.1989.5.169
PMID: 2623382
ISSN: 1043-0733
eISSN: 2332-4988
Grant note: CA18420 / NCI NIH HHS
Language: English
Date published: 1989
Academic Unit: Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
Record Identifier: 9984359667702771

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