5FU treatment

The protective effect of CVS against indigenous bacterial infection caused by 5FU treatment [50,51] has been examined. At 5 days after 5FU... 

Thus, CVS induced some CSF, contributing to the accelerated hematopoiesis and early recovery of the number of viable colonies, which resulted in the protection of mice against indigenous infection by 5FU treatment. 

In normal mice, an intraperitoneal 250 mg/kg 5FU treatment is not lethal, but 100% mortality was observed within 2 weeks after the same dose of 5FU treatment in mice bearing Meth A tumors. The mean survival time of Meth A-inoculated, 5FU-treated mice (23.1 1.2 days) is significantly shorter than that of 5FU-untreated tumor-bearing mice (29.0 3.5 days). In CVS-administered tumor-bearing mice, the mean survival time is 48.5 8.7 or 37.6 6.2 days with or without 5FU treatment, respectively. With respect to the antitumor effect as determined by tumor growth, 5FU was... 

First generation of topi inhibitors were developed as drugs from camptothecins, a family of compounds derived from wood and bark of the Chinese tree Camptotheca acuminata) [9, 10], Many of these are already in clinical use or clinical trials, including irinotecan, topotecan, exatecan, rubitecan, and lurtotecan. Irinotecan (CPT-11) is bioactivated in liver by carboxylesterase to the active metabolite SN-38, 1000-fold more active [11]. Irinotecan received in 1998 FDA approval for treatment of metastatic colorectal cancer after failure of treatment with 5FU [12],... 

Most of the normal CDF1 mice died between 11 and 17 days after the intraperitoneal treatment with 500 mg/kg of 5FU. The 50% lethal dose (LD50) of 5FU was 400 mg/kg, whereas the LD50 was increased to 520 mg/kg or 700 mg/kg when CVS was pre-injected with 50 mg/kg or 500 mg/kg, respectively (data not shown). Thus, CVS reduced the adverse effect of 5FU. 

The number of leukocytes after treatment with a sub-lethal dose of 5FU decreased and reached its lowest level on day 7, followed by gradual recovery (data not shown). In the CVS group, the overall kinetics were almost the same, but the levels of leukopenia on day 4 were weaker and a rapid recovery was observed. CVS administration did not influence the total leukocyte counts or the differential counts in untreated normal mice (data not shown). 

Introduced about 40 years ago, Fluorouracil 177 (5-fluorouracil, also called 5FU) is used for treatment of various types of cancer, including bowel, breast, stomach, and gullet (esophagus) cancer. Numerous methods of synthesis of 177 are reported. The 2-fluoroenals, -enones, and -enesters may serve as building blocks for the... 

LA. Infusion For the treatment of colorectal metastases to liver, systemic 5- fluorouracil (5FU) yielded a 20% response rate. FUDR infused through a catheter placed surgically or percutaneously into the hepatic artery, had response rates ranging from 32% to 88% depending upon the criteria utilized. Despite effective control of hepatic disease, extrahepatic metastases were usually the major cause of death. At MDACC, the intraarterial infusion of FUDR (100 mg/m /day-h5) and mitomycin C (10 mg/m ) yielded a response rate of 61% in previously untreated patients, and 45% in patients who failed to respond to previous intravenous 5FU. A response rate of 52% was found with the intraarterial infusion of FUDR and cisplatin (100 mg/m ). The median survival time for the responders was 16 months. 

Chemoembolization Chemoembolization with the combination of Ivalon and FUDR (800 mg), mitomycin C (10 mg), or cisplatin (150 mg) for colorectal hepatic metastases led to no significant improvement in response or survival. Yamashita et al. (1993), who treated 68 patients with various hepatic metastases using iodized oil and chemotherapeutic agents,noted a response rate of 22% and a median survival of 10 months. A similar result was observed by Inoue et al. (1989), i.e., a partial response rate of 16% and a median survival period of 11 months. We currently do not perform chemoembolization in patients with metastatic colorectal carcinoma because the survival rates have not improved compared to the less aggressive approach of intraarterial chemotherapy. However, Lang and Brown (1993) and Pentecost et al. (1992) are encouraged by their results for chemoembolization of hepatic metastases from colorectal cancer and they believe that the technique can be recommended as palliative treatment. More recently, Pajkos et al. (1998) treated 41 patients with metastatic colorectal carcinoma to the liver with chemoembolization consisting of Adriamycin (50 mg), mitomycin C (8 mg), cisplatin (50 mg), or carboplatin (150 mg), Lipiodol (10 ml), and starch microspheres every 6 weeks, as well as systemic 5FU (425 mg/m ) and leucovorin 20 mg/m for 5 days every 28 days. The response rate was 68% with a median survival time of 15 months. 

At MDACC, of the 100 patients with RCC treated by renal artery embofization and reported by Wallace et al. (1981), 49 patients with metastases from renal carcinoma were treated by renal artery embolization of the primary neoplasm to debulk the tumor in preparation for systemic treatment with 5FU, mitomycin C, and interferon-a. Embolization proved to be as effective in reducing tumor cell population as nephrectomy. This regimen had a 35% response rate (Sella et al. 1992). 

---