Results from a recent international clinical trial led by investigators at the Dana-Farber Cancer Institute showed that a medication developed 50 years ago and abandoned due to its toxicity, might extend metastatic colorectal cancer patients’ lives. The study results, which were recently published in the New England Journal of Medicine, show that the drug agent TAS-102 was also able to delay cancer progression with minor adverse side events.
The researchers mentioned that the results were particularly impressive as half the patients did not benefit from chemotherapy treatment with fluoropyrimidines but TAS-102 delayed disease progression, indicating the condition affects a biochemical pathway other than 5-FU, which might serve as an alternative to traditional treatments.
“Colorectal cancer is the second most common cause of cancer deaths [after lung cancer] in the United States and is an enormous health problem around the world,” said the study’s lead author, Robert J. Mayer, MD, faculty vice president for academic affairs, medical oncologist and colorectal cancer researcher at Dana-Farber in a news release . “To have a well-tolerated, effective new drug in a cancer that is so prevalent is good news for patients.”
The study was a Phase 3 international clinical trial conducted in institutions across the US, Japan, Europe and Australia involving 800 patients suffering from progressive metastatic colorectal cancer. Patients were assigned to receive treatment with TAS-102 or with a placebo.
Results revealed that patients who received TAS-102 had a median survival period of 7.1 months in comparison to 5.3 months for patients who received the placebo. Patients in the TAS-102 group had a median time of disease progression of 5.7 months in comparison with 4.0 months for patients who received the placebo.
The drug agent behind the efficacy of TAS-102 is a component called trifluridine, developed in the 1950s, at about the same period as 5-FU, with evidence indicating its capacity to block an enzyme called thymidylate synthase, which cells need for survival.
Trifluridine integrates cancer cells’ DNA but in the past was found to be toxic. Taiho Pharmaceutical began analyzing, about 15 years ago, treatments with trifluridine combined with tipiracil hydrochloride, a drug that blocks the metabolism of trifluridine. Upon this combination, trifluridine could exert only its beneficial effect without revealing its toxicity.
Evidence from studies conducted in Japan in colorectal cancer patients showed encouraging results, leading to small trials in the U.S. conducted by investigators at Dana-Farber and other research centers.
“When we first saw the data from the trial, they were unequivocally positive,” Dr. Mayer said. “The benefits of the drug were observed in patients regardless of age, ethnicity, sex, or the molecular make-up of their tumor.”
The next step will be to test TAS-102 in combination with other drugs that are customarily used in conjunction with 5-FU, and compare results, Dr. Mayer explained in the news release.