RESUMEN
The cytotoxic activity of Iso(thio)cyanate derivatives and some new organophosphorus compounds were determined,using MTT assay against human hepatocellular carcinoma (HepG2) and adenocarcinoma breast (MCF-7) incomparison with the reference drug 5-flurouracil. All the selected products have been tested and showed concentrationdependent increase in the growth inhibition percentage against HepG2 and MCF-7. Where, the thietane derivativesrevealed anticancer activity with IC50 (20, 8.9 µg/ml) against HepG2 and (20, 10.3 µg/ml) against MCF-7; while,thiazinane compounds showed IC50 (12.7, 32.5 µg/ml) against HepG2 and (20 and 20 µg/ml) against MCF7. The newly synthesized azetidines showed anticancer activity with IC50 (13.5 and 32.5 µg/ml) against HepG2and IC50 (10 and 25.9 µg/ml) against MCF-7 cancer. Moreover, azetidinedione compound exhibited more potentactivity than the azetidinone with both types of cancer cell lines. In addition, the cytotoxic activity of the iso(thio)cyanates, and malonamic acid methyl ester compound were also investigated. 4-Methoxyphenyl isothiocyanate andmethylisothiocyanate, with IC50 (25.9, 12.3 and 40, 20 µg/ml), respectively, against HepG2 and MCF-7 cancer cells.1, 2-Dichloro-4-isocyanato-benzene was similar in potency to the known anticancer drug 5-flurouracil with IC50 (5.3µg/ml) versus 5 µg/ml for 5-flurouracil against MCF-7. While, malonamic acid methyl ester compound had no effecton both types of cancer cell lines.
RESUMEN
PURPOSE: Fluorouracil (5-FU) and leucovorin combination therapy have shown synergistic or additive effect against advanced colorectal cancer, but the frequency of mucositis and diarrhea is increased. Most previous studies have used high dose leucovorin (300~500 mg/m2). However, some studies of oxaliplatin and 5-FU with low-dose or high-dose leucovorin in Korea have shown similar response rates. Therefore, we studied the necessity of leucovorin and evaluated the objective tumor response rates and toxicities of a regimen of oxaliplatin and 5-FU without leucovorin every 2 weeks in metastatic colorectal cancer patients. MATERIALS AND METHODS: Twenty-four patients with metastatic colorectal cancer were enrolled between January 2002 and March 2003. Patients received 85 mg/ m2 of oxaliplatin on day 1, a bolus 5-FU 400 mg/m2 on day 1 and a continuous 5-FU infusion at 600 mg/m2/ 22 hours days 1 and 2, every 2 weeks. RESULTS: Of the 24 patients treated, 17 patients received previous 5FU with leucovorin and/or other chemotherapy. Three patients could not be evaluated. Five partial responses were observed with overall response rate of 21% (n=24). Of the previous chemotherapy group (n= 17), 4 partial responses were observed with response rate of 24%. Median overall survival was 18 months (range 4~32 months) and median progression free survival was 4 months (range 2~6 months). This regimen was well tolerated and only 1 grade 3 anemia was observed. CONCLUSION: Oxaliplatin/5-FU combination therapy without leucovorin achieved a relatively high response rate even in patients resistant to the previous 5-FU chemotherapy, and toxicity was minimal.