European Journal of Cancer: Highlights of Issue 38:04

Raltitrexed or 5-FU
Toxicity - Response - Survival

Raltitrexed or 5-fluorouracil for the treatment of advanced colorectal cancer

Raltitrexed and 5-fluorouracil are both inhibitors of thymidylate synthase. However, they have differing mechanisms, pharmacokinetics and pharmacodynamics. Cunningham and colleagues review data from phase II and III trials of these two cytotoxics for the treatment of advanced colorectal cancer patients. For most of the studies, both survival and response rates were similar. Raltitrexed treatment did result in some increased toxicity and the authors suggest guidelines to minimise the incidence of serious side-effects. These included monitoring the renal function of the patient, as approximately 50% of raltitrexed is excreted unchanged in the urine, as well as the prompt treatment of symptoms, particularly diarrhoea and neutropenia.

A current perspective of muscle invasive bladder cancer

5-year survival for patients with muscle invasive bladder cancer is approximately 50% and can be as low as 25-35% for those considered high risk (pT3-pT4, pN+ M0). Dr. Sternberg therefore discusses in her Current Perspective the many challenges to be faced in this field. She outlines the importance of taking a multimodal approach with collaboration between the many disciplines involved. From the evidence in the literature, she states that it is not yet clear whether neoadjuvant or adjuvant chemotherapy should be given, although neoadjuvant chemotherapy may be useful in preserving the bladder and thereby maintaining a better quality of life. She concludes “the international adjuvant chemotherapy trial co-ordinated by the EORTC will hopefully clarify some of these unanswered questions”.

Increased matrilysin expression following preoperative radiotherapy treatment of rectal cancer patients

The overexpression of matrilysin (MMP-7), a matrix metalloproteinase, in colorectal cancer patients is thought to be associated with an increased metastatic potential and Dukes’ stage. Kumar and colleagues studied in this issue the effects of preoperative radiotherapy (25Gy, 5 fractions, 5 days), that is increasingly being given to patients with resectable rectal cancer as an adjuvant treatment, on MMP-7 gene expression. Using a quantitative Reverse Transcriptase Polymerase Chain Reaction (RT-PCR) technique, applied to 30 tumour samples derived from 15 patients, they showed that preoperative radiotherapy led to a 6-7-fold increase in MMP-7 expression in the tumour tissue. No change was observed in the control tissues (n=12). The authors suggest that therapies aimed at inhibiting MMP-7 expression may be useful.

Back . . .