A combination therapy with copper nicotinate complex reduces the adverse effects of 5-fluorouracil on patients with hepatocellular carcinoma
Muhammad A.M. El-Saadani
5-Fluorouracil (5-FU) as chemotherapy in cases of hepatocellular carcinoma (HCC), was found to initiate hepatotoxic injuries, ascites, leucopenia, thrombocytopenia and myelosupression that limit its use. Therefore, this work was conducted to investigate whether the combination of copper (I)–nicotinate complex [CuCl (HNA)2] with 5-FU may overcome such a drug resistance. Forty-eight patients with HCC were therapy-naïve and treated with 5-FU (12 mg/kg/day) for 5 days in 2 cycles with 4 weeks in between. Twenty-four of them were simultaneously given oral doses of copper (I)–nicotinate complex (0.8 mg/kg/day) started with the 5-FU treatment. The combined therapy of CuCl (HNA)2 with 5-FU could improve the prognosis of HCCpatients. Improvement of liver function was presented by significant reduction of serum bilirubin (p<0.001), transaminases and alkaline phoshatase (p<0.05). The copper complex prevented hypoproteinaemic and hypoalbuminaemic effects of 5-FU and rendered the prothrombin time to its normal value (p<0.001). Superoxide dismutase, ceruloplasmin and immunoglobulins IgG showed significant increases (p<0.001), while serum copper and lipid peroxides were reduced (p<0.001). Thrombocytopenia, leucopenia and other myelosuppressive effects of 5-FU were reduced by the co-administration of CuCl (HNA)2. In conclusion the combination with CuCl (HNA)2 given in such a dosage schedule mitigated the most frequent toxicities associating 5-FU administration and enhanced defense mechanisms against oxidative stress.