Effect of oral adjuvant therapy with Carmofur (HCFU) for distant metastasis of colorectal cancer

Abstract

Background. The effectiveness of adjuvant chemotherapy for colorectal cancers after curative resection has been reported recently; this study was performed to clarify the reasons of for this effectiveness, which have been unclear. Methods. Two joint prospective clinical randomized studies were performed. In the first study, of patients operated on between July 1, 1981 and June 30, 1983, at 41 Centers in the Tokai district, 172 patients with colorectal cancer were allocated to two groups. In the control group, mitomycin C (MMC) was given eight times intravenously in the 4 weeks after surgery. The other group, in addition to receiving the same regimen as the controls, received oral administration of 1-hexylcarbamoyl-5-fluorouracil (HCFU) at 600 mg/day for at least 6 months after the 4-week MMC treatment. In the second study of patients operated at 7 Centers in the Tokai district between October 1, 1987 and September 30, 1990, 173 patients with colorectal cancer were allocated to two groups after surgery, a control group receiving no HCFU, the other group receiving HCFU at 0.8 mg/kg per day orally, for 1 year, beginning 4 weeks after the operation. Results. In the first study, the cumulative 10-year survival rate of the MMC + HCFU group was higher than that of the MMC-alone group (P < 0.05). In the second study, the cumulative 5-year disease-free survival rate of the HCFU group was higher than that of the control group (surgery alone; P < 0.05). In patients with colon cancers, the rate of distant metastases for all evaluable patients was lower in the MMC + HCFU group than in the MMC-alone group in the first study (P < 0.05), and the rate was lower in the HCFU group than in the surgery-alone group in the second study (P < 0.02). Conclusion. The effectiveness of HCFU in reducing the disease-free survival rate appeared to be mainly due to its preventive effect on distant metastases.

Randomized trial of the efficacy of adjuvant chemotherapy for colon cancer with combination therapy incorporating the oral pyrimidine 1-hexylcarbamoyl-5-fluorouracil

“…The greatest factor affecting the prognosis of colon cancer is hepatic recurrence, whose control is considered to be the most important factor in improving the prognosis [17]. The results of the present study, which demonstrated control of hepatic recurrence, were consistent with the results obtained with HCFU by other various investigators [9,11,17], and the efficacy of HCFU in the prevention of hepatic recurrence was demonstrated.…”

“…The greatest factor affecting the prognosis of colon cancer is hepatic recurrence, whose control is considered to be the most important factor in improving the prognosis [17]. The results of the present study, which demonstrated control of hepatic recurrence, were consistent with the results obtained with HCFU by other various investigators [9,11,17], and the efficacy of HCFU in the prevention of hepatic recurrence was demonstrated. In the stratification analysis of DFS using Dukes' classification, the results for the chemotherapy group were good, with statistical significance in Dukes' B and a tendency to significance in Dukes' C. Also, the chemotherapy group had significantly better RFI in Dukes' B and C. Not only Dukes' C patients but also those in Dukes' B were considered to have a high risk of postoperative hepatic recurrence, and combination chemotherapy incorporating HCFU was thought to have potent effectiveness against hepatic recurrence in these patients.…”

Light-driven liquid metal nanotransformers for biomedical theranostics

“…We therefore expected the destruction of nanocapsules by NIR laser light to be useful for the controlled release of drugs at targeted locations. To test this hypothesis, we encapsulated carmofur, a pyrimidine analogue used as an antineoplastic agent 51 , into LM nanocapsules. Ultraviolet–visible–NIR spectra showed a characteristic peak from carmofur at ∼266 nm after encapsulation; this corresponded to a slight shift to the red compared to the original carmofur solution (peak at 259 nm), caused by interaction of the drug with the LM and lipid shell ( Supplementary Fig.…”

Sphingolipid Metabolism in Glioblastoma and Metastatic Brain Tumors: A Review of Sphingomyelinases and Sphingosine-1-Phosphate

“…A study in TNBC found that a nanoparticle containing docetaxel and fingolimod could abrogate lymphopenia while still blocking progression [ 183 ]. Carmofur, a derivative of 5′ fluorouracil and an inhibitor of acid CDase, has been used as adjuvant therapy in colorectal cancer patients to prevent metastasis [ 184 ]. The drug, which is known to cross the BBB, has been used for years in Japan as maintenance therapy following standard of care but has not been subjected to FDA approval in the United States [ 185 ].…”