The CancerWeb Report, What's New In Cancer: February, 1997
Colorectal Cancer

• Aspirin, a further study on how it might reduce the incidence of colon cancer - A number of epidemiologic studies have indicated that aspirin, and perhaps some other NSAIDS, may reduce the incidence of colon cancer by between 10% and 80%, with most studies yielding a figure of around 50%. One study found, in contrast, a 50% increase in risk. A common feature in the studies reporting reduced risk has been fairly regular use, a minimum of twice weekly, for prolonged periods - 5 or 10 years have been indicated in different studies. How aspirin might have this protective effect is a mystery, although it is believed that it is related to effects on the production of certain substances characteristic of inflammation and pain. A report from researchers at Loyola University in Maywood, Illinois, in the February, 1997 issue of Clinical Cancer Research confirms this connection. They found that one aspirin tablet (325 mg) taken daily for 60 days reduced the concentrations of an inflammatory substance, prostaglandin E2, by 50% or more through its inhibition of the enzyme cyclooxygenase. Another 60-day treatment caused a further but not significant reduction, and doubling the dose also gave a greater reduction but at the cost of much more stomach upset. (Frommel, Clin Cancer Res 3:209, 1997)

  Editor's Comment: - This article does provide information on one link in the chain connecting aspirin with reduced colon cancer. The next link would be the known effect of prostaglandin E2 in suppressing the proliferation and activation of T-cells, macrophages and natural killer cells, types of white blood cells that are known to be responsible for immune attack on tumor cells. There is evidence that colon cancer cells have higher levels of aspirin's target enzyme, cyclooxygenase, which might make the early tumor cells more susceptible than normal colon. However, since other NSAIDS such as sulindac, which do not affect cyclooxygenase also have antitumor activity, it cannot yet be said that the cancer preventive action is explained. There may be other pathways that are affected, or different drugs may work in different ways.

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• A bimonthly treatment regimen more effective for advanced colorectal cancer - A French study from researchers in Dijon, Paris and Lille, published in the February, 1997 issue of the Journal of Clinical Oncology, concluded that a bimonthly regimen was better than a monthly one in terms of response rate and reduced toxicity. They compared monthly 5-day 5-fluorouracil (5-FU) injection and low-dose leucovorin with bimonthly high-dose leucovorin and 5-FU infusion. Response rates in 348 patients with advanced colorectal cancer were 14.4% for monthly versus 32.6% for bimonthly, and median survivals were 22 and 27.6 weeks, respectively. Overall survival was not increased significantly, however. The monthly treatment was more toxic. (De Gramont, J Clin Oncol 15:808, 1997)

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• Tomudex a little better than 5-fluorouracil plus leucovorin for advanced colorectal cancer - 5-fluorouracil (5-FU) has been the mainstay of chemotherapy for colorectal cancer for so long, without being a highly effective drug, that it is no surprise that there are continuous efforts to find a better replacement. One possible alternative is Tomudex (raltitrexel), but an article in the November, 1996 issue of Annals of Oncology concluded that the response rate with this drug was only slightly better than with 5-FU plus leucovorin (19% versus 14%). Tomudex also appeared to have a lower incidence of side-effects and a more convenient dose scheduling that required fewer hospital visits. The international Tomudex Colorectal Cancer Study Group concluded that Tomudex is a viable alternative whose use in combination should be explored. (Cunningham, Ann Oncol 7:961, 1996)