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COLORECTAL CANCER (CRC)
Colorectal cancer is a cancer that starts in the colon or the rectum. These cancers can also be named colon cancer or rectal cancer, depending on where they start. Colon cancer and rectal cancer are often grouped together because they have many features in common. Most colorectal cancers are due to old age and lifestyle factors with only a small number of cases due to underlying genetic disorders. Colorectal cancer is the third most common cancer to affect both men and women, and the third-leading cause of cancer-related mortality.
ALL CURRENT FOLATE-BASED THERAPIES USED IN CANCER TREATMENT ARE PRODRUGS THAT REQUIRE MULTIPLE ACTIVATION STEPS
The chemotherapy drug 5-fluorouracil (5-FU) in combination with leucovorin/levoleucovorin is used in large quantities as the core treatment for colorectal cancer. 5-FU works by inhibiting an enzyme needed for making DNA. By adding folates like leucovorin or levoleucovorin to the 5-FU treatment, response rates are increased from around 10% to 30%. Folates are incorporated in almost all CRC treatment regimes (Among them are: FOLFOX, 5-FU and FOLFIRI regimes).
ARFOLITIXORIN – DOES NOT REQUIRE METABOLIC ACTIVATION TO EXERT ITS ACTION
As arfolitixorin is given as the active metabolite, it has the potential to enable all patients to benefit more fully from the core 5-FU and folate treatment, and significantly improve the treatment outcome in patients with colorectal cancer.
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Pharmacokinetic and pharmacodynamic data from clinical trial ISO-CC-002
Pharmacokinetics and pharmacodynamics investigation of arfolitixorin (Modufolin®) in Plasma, Tumor and Adjacent Mucosa in Patients With Colon Cancer’ provide strong rationale for the potential benefits and so the further development of [6R]-MTHF.
[one_half]Methylene THF ([6R]-MTHF) levels in Mucosa
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[one_half_last]Methylene THF ([6R]-MTHF) levels in Tumor
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Significantly higher Methylene THF ([6R]-MTHF) concentrations were seen in tumor tissue after two equimolar dose levels of arfolitixorin (Modufolin®) or leucovorin, accross all dosages trialed, (analysis of variance; P = 0.0017)
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[one_half_last]All folate drugs used today, including, leucovorin and levoleucovorin, need a multi-step activation to MTHF. These results, from a gene expression study, clearly show the correlation between the expression level of certain genes involved in this multi-step activation and the survival of mCRC patients after treatment with 5-FU and leucovorin, a commercially available reduced folate.[/one_half_last]
After six months, there is 50% chance of survival for patients with low expression levels and 67% for those with high expression levels, or a 1/3 (33%) better chance of survival in patients with high expression levels.
After eighteen months there is 15% chance of survival for patients in low expression levels and 35% for those with high expression levels or more than a 100% better chance of survival in patients with high expression levels.
[one_half]These results show that the probability of three year survival is 30% higher among patients with high expression levels of the identified folate relevant genes.
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Last updated 03-01-2019
