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5-Fluorouracil (5-FU) has been widely used for over 30 years. Recently, investigators have described interactions between toxicity with 5-FU and age and gender. Pharmacokinetics of infusional 5-FU are known to be gender dependent, with drug clearance being lower in females. The full impact of age and gender on both toxicity and response has not been fully explored and is worthy of further investigation. 439 patients were entered into a phase III trial comparing a novel thymidylate synthase (TS) inhibitor Tomudex (raltitrexed, formerly ZD1694) with 5-FU and leucovorin (LV) for the treatment of advanced colorectal cancer. Approximately 20-24% of patients in each treatment group were aged 70 years or older and 41% of the patients were female. In a multiple regression analysis, female patients receiving 5-FU + LV experienced significantly more grade 3/4 leucopenia, whilst those receiving raltitrexed had more rises in transaminase levels. Grade 3/4 leucopenia and mucositis were significantly correlated with age (especially > 70 years) only in patients receiving 5-FU + LV. Patients receiving 5-FU + LV were significantly more at risk of experiencing grade 3/4 haematological and non-haematological toxicity in the first three cycles than patients receiving raltitrexed. Female gender and increased age predict for increased grade 3/4 toxicity in patients receiving modulated 5-FU. Further studies with modulated 5-FU which utilise a modified dose reduction schema for female patients, or patients aged 70 years or over, may be appropriate.

Original publication

DOI

10.1016/s0959-8049(98)00259-7

Type

Journal article

Journal

Eur J Cancer

Publication Date

11/1998

Volume

34

Pages

1871 - 1875

Keywords

Adult, Age Factors, Aged, Antidotes, Antineoplastic Combined Chemotherapy Protocols, Colorectal Neoplasms, Female, Fluorouracil, Hematologic Diseases, Humans, Leucovorin, Male, Middle Aged, Quinazolines, Sex Factors, Thiophenes