W. Testi

TREATMENT OF ADVANCED COLORECTAL CANCER WITH HIGH-DOSE INTENSITY FOLINIC ACID AND 5-FLUOROURACIL PLUS SUPPORTIVE CARE

This randomised clinical trial, involving patients with advanced colorectal cancer, was carried out to compare the effectiveness of accelerated folinic acid (FA) plus 5-fluorouracil (5-FU) with that of the conventional regimen of 5-FU alone. Both regimens were administered with simulataneous supportive care. 185 patients were eligible: 94 were randomly allocated to receive FA 200 mg/m2 i.v. plus 5-FU 400 mg/m2 i.v. on days 1-5 every 3 weeks; and 91 to receive 5-FU 400 mg/m2 i.v. on days 1-5 every 4 weeks. The response rate was 33.3% in the accelerated FA/5-FU and 18.6% in the 5-FU arm (P = 0.045). Median survival was 13.5 months in the FA/5-FU arm and 7.5 months in the 5-FU arm (P = 0.039). Toxicity was mild and slightly more pronounced in the FA/5-FU arm (P = 0.078). This study indicates that, in patients with advanced colorectal cancer, accelerated chemotherapy with FA and 5-FU and simultaneous supportive care is capable of achieving a higher response rate and longer survival than conventional 5-FU alone, without severe toxicity.

Behavior of Enzymes Involved in Purine Nucleotide Metabolism in Tumors

Alterations in nucleotide metabolism have been observed in all experimental tumors. The “biosynthetic enzymes” and, specifically, phosphoribosylamidotransferase, which is the “key biosynthetic enzyme”, are clearly enhanced in experimental tumors, whereas “catabolic enzymes”-adenylate deaminase, S’-nucleotidase, purine nucleoside-phosphorylase and, specifically, xanthine oxidase (the “key catabolic enzyme”) — are decreased. The phosphoribosylamidotransferase/xanthine oxidase ratio increases with a characteristic pattern and is related to the aggressivity and invasiveness of the tumor1, 2.

Pattern of Methylated Purine Bases in Urine of Cancer Patients. Analysis by Mass Spectrometry

Methylated purine bases are constituents of both RNA and DNA. tRNA contains the highest number of such compounds. The methyl groups play different roles: they avoid “base pairing”, they allow codon identification, they recognize the enzyme aminoacyl tRNA synthetase, and they participate in the aminoacid transfer from tRNA to ribosomes1.

Radioimmunoassay of Folic Acid and its Correlation with Age

Folic acid is a very well known coenzyme that acts as carrier of monocarbon units and has a great importance in the synthesis of purine nucleotides. It occurs in vegetables as triand hepta-glutamate derivatives. The human body is absolutely unable to synthesize it.