Sorafenib is the only approved targeted agent as the first line systemic therapy for treatment of advanced hepatocellular carcinoma (HCC). However, the improvement of survival duration under 3 months is far from clinical satisfactory and most patients experience disease progression within 6 months after sorafenib therapy. Unfortunately, second line systemic therapy after treatment failure of sorafenib was not established and there were no clear guidelines for salvage treatment modalities. Recently, studies suggests that combination of sorafenib and single cytotoxic agent can be relatively effective and safe strategy that achieves promising rates of local and systemic control in advanced HCC patients. Based on above suggestions, we herein offer our experience of a case achieved complete remission by combination therapy of sorafenib and tegafur in the patient with progressed disease after sorafenib therapy.
Carcinoma, Hepatocellular* ; Disease Progression ; Humans ; Salvage Therapy ; Tegafur* ; Treatment Failure

The second-generation oral anticancer agent UFT is a combination of uracil, which has fluorouracil's (5-FU) degradation-inhibitory effect, and tegafur, which is slowly converted to 5-FU in vivo, and UFT shows a higher 5-FU concentration in the tumor tissues than is achieved by tegafur alone or with comparable doses of intravenous 5-FU. Mucocutaneous side reactions induced by UFT are rare and these include photosensitivity of the lichenoid and eczematous types, acral erythema, hyperpigmentation, palmoplantar keratoderma and scleroderma-like reactions, and discoid lupus erythematosus (DLE)-like eruption. However, there has been no report in the Korean medical literature on patients presenting with a DLE-like eruption associated with UFT. So, we report here a case of DLE-like eruption induced by oral UFT.
Erythema ; Fluorouracil ; Humans ; Hyperpigmentation ; Keratoderma, Palmoplantar ; Lupus Erythematosus, Discoid ; Tegafur ; Uracil

Tegafur is a fluoropyrimidine structurally similar to 5-fluorouracil, used in the treatment of advanced gastrointestinal neoplasms. Mucocutaneous side reactions induced by this agent are rare and include photosensitivity of lichenoid and eczematous types, acral erythema, hyperpigmentation and palmoplantar keratoderma. However, to our knowledge, there has been no report of concurrent development of eruptions of two types in a patient. We describe a female patient with breast cancer, presented with combined features of acral erythema and hyperpigmentation due to oral tegafur.
Breast Neoplasms ; Erythema* ; Female ; Fluorouracil ; Gastrointestinal Neoplasms ; Humans ; Hyperpigmentation* ; Keratoderma, Palmoplantar ; Tegafur*

PURPOSE: Tegafur, an oral prodrug of 5-fluorouracil (5-FU), has been used in the treatment of gastric cancers. UFT (tegafur + uracil) has been developed to enhance the efficacy of tegafur. This study was conducted to assess the pharmacokinetics (PK) of tegafur in gastric cancer patients given the ECU-E regimen (epirubicin, cisplatin, UFT-E, an enteric-coated formula of UFT). A preliminary evaluation of antitumor efficacy and toxicity of ECU-E regimen was also performed. MATERIALS AND METHODS: Of the 32 gastric cancer patients registered for the ECU-E regimen, 8 participated in the PK study. The plasma concentration of tegafur was determined using HPLC. RESULTS: Seven out of the 8 patients were evaluable for response after 2 cycles, and showed 3 partial responses, 1 stable disease and 3 progressive diseases. No major toxicities were observed. Plasma profiles of the tegafur after the first dose showed significant differences in the amount and rate of absorption, i.e., rapid absorption group vs. slow absorption group. The level of C(max) in the rapid absorption group was 1.8 fold higher, and the AUC(0-5h) 4 fold greater, than those in the slow absorption group, nonetheless, the steady state concentrations showed no significant difference. These data indicate that the different absorption rates may not affect the overall exposure to tegafur. The patients with low Cp(ss, peak) showed poor efficacy compared to those with high Cp(ss, peak), suggesting that the concentration of tegafur may be one of the pharmacodynamic determinants in patients administered with ECU-E. CONCLUSION: This study evaluated the pharmacokinetics of tegafur in gastric patients given the ECU-E regimen, and provides preliminary data on the relationship between the plasma tegafur level and the efficacy, which warrants further evaluation.
Absorption ; Chromatography, High Pressure Liquid ; Cisplatin* ; Epirubicin* ; Fluorouracil ; Humans ; Pharmacokinetics* ; Plasma ; Stomach Neoplasms* ; Tegafur* ; Uracil

A mixture of tegafur and uracil (TEGASIL) is a common antineoplastic agent. Tegafur is a fluoropyrimidine structurally similar to 5-fluorouracil (5-FU); uracil slows the degradation of 5-FU by dihydropyrimidine dehydrogenase, which results in higher 5-FU concentrations in tumors. Mucocutaneous side effects induced by this agent are rare and include photosensitivity of lichenoid and eczematous types, acral erythema, hyperpigmentation and palmoplantar keratoderma. However, there have been no reports of fixed drug eruption associated with TEGASIL. We report here on a case of fixed drug eruption due to oral TEGASIL.
Dihydrouracil Dehydrogenase (NADP) ; Drug Eruptions ; Erythema ; Fluorouracil ; Hyperpigmentation ; Keratoderma, Palmoplantar ; Tegafur ; Uracil

Tegafur [1-(tetrahydro-2-furyl)-5-fluorouracil], the prodrug of 5-fluorouracil, is an anticancer agent. Several cutaneous reactions have been reported following systemic 5-fluorouracil for the treatment of malignancies. We report a patient with marked inflammation of the actinic keratosis following the use of tegafur for stomach carcinoma. The side-effect with 5-fluorouracil was beneficial as most actinic keratosis cleared following the inflammatory reaction. Dermatologists and oncologists should be aware of this potential side-effect, not only because it may become more prevalent but, most importantly, because it is not an allergic reaction to 5-fluorouracil but a dose-dependent response, and the chemotherapy may be continued in most patients.
Actins* ; Drug Therapy ; Fluorouracil* ; Humans ; Hypersensitivity ; Inflammation ; Keratosis, Actinic* ; Stomach ; Tegafur

BACKGROUND: UFT/oral leucovorin (LV) provided a safer, more convenient oral alternative to bolus i.v. 5-Fluorouracil/LV regimen for advanced colorectal cancer while producing equivalent survival. We evaluated the efficacy and safety of a combination of oxaliplatin and UFT/LV in patients with advanced colorectal cancer. METHODS: From January 1999 to December 2001, a total 28 patient with metastatic or relapsed colorectal cancer were enrolled in this study. Treatment was consisted of oxaliplatin 130 mg/m2 i.v. for 2 hours on day 1, and UFT 300 mg/m2 p.o. and LV 30 mg p.o. on day 1-21. Chemotherapy repeated every three weeks until disease progression. RESULTS: Of the 28 patients, 1 complete response and 10 partial responses were observed. The overall response rate was 39.3%. The estimated median time to progression and survival were 6.0 months and 18.2 months, respectively. Peripheral neuropathy was the most common adverse effect. But, peripheral neuropathy was mild (grade 1, 2) and reversible. From the 129 cycles analyzed, grade 3, 4 adverse effects were observed only 3% included neutropenia (1.5%), and thrombocytopenia (1.5%). There were no treatment-related deaths. CONCLUSION: This combination of oxaliplatin and UFT/oral leucovorin is active and feasible in patients with advanced colorectal cancer. The regimen deserve further evaluation in a phase III prospective study.
Colorectal Neoplasms* ; Disease Progression ; Drug Therapy ; Drug Therapy, Combination* ; Humans ; Leucovorin* ; Neutropenia ; Peripheral Nervous System Diseases ; Tegafur ; Thrombocytopenia ; Uracil

AIMA new proliposomal technology was used to trap several drugs, such as tegafur, silymarin, cistanosides, oleanolic acid. And then these proliposomal characters were studied.

METHODSThese proliposomes formed liposomes after mixing with water. And then the liposomal morphology was determined by electron microscope, and the liposomal particle size determined by particle sizes instrument. The trap efficiency was determined by the column chromatography, and then the influence factors on the trap efficiency were investigated.

RESULTSThe liposomes looked round, some with multiply layers, the particle was small, and the xi potential was about - 30 mV. The trap efficiency changed with the partition coefficient and pH. When the partition coefficient and pH increased, the trap efficiency increased. Furthermore, the trap efficiency was not influenced by the molecular weight.

CONCLUSIONThis kind of liposomal technology trapped the drugs efficiently, and the lipophilic drugs were trapped more easily. Some Chinese traditional drugs could be trapped too.

Hydrogen-Ion Concentration ; Liposomes ; chemistry ; Oleanolic Acid ; administration & dosage ; Particle Size ; Silymarin ; administration & dosage ; Technology, Pharmaceutical ; Tegafur ; administration & dosage

AIMTo evaluate in vivo distribution characteristics of a novel proliposomal preparation of tegafur in rats.

METHODSConcentrations of tegafur in tissues and plasma were measured by HPLC following intragastric gavage of the proliposomal preparation of tegafur (PL-FT207) or aqueous suspension of tegafur tablet (T-FT207) to rats. And the pharmacokinetic parameters including the area under the concentration-time curve (AUC), relative tissue efficiency and the maximum drug concentration were calculated.

RESULTSFollowing intragastric gavage of PL-FT207 or T-FT207 to rats, AUC was significantly increased in plasma, liver, kidney, colon and lung (P < 0.01) of PL-FT207 group in contrast to that of T-FT207 group, the relative tissue efficiencies of these tissues were 1.36-1.57, the maximum drug concentrations of brain and lung of PL-FT207 group were significantly declined (P < 0.005).

CONCLUSIONThe novel proliposomal preparation of tegafur is able to promote drug absorption in gastro-intestine, increase drug distribution in kidney, liver, colon and lung, and decrease the maximum drug concentration in brain and heart, thus providing scientific basis for further studies on this preparation.

Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; pharmacokinetics ; Area Under Curve ; Drug Carriers ; Drug Stability ; Female ; Liposomes ; Male ; Random Allocation ; Rats ; Rats, Wistar ; Tegafur ; administration & dosage ; pharmacokinetics ; Tissue Distribution

OBJECTIVEThis study was to investigate the molecular biomarkers of apoptosis induced by BH3 mimetic S1 in human primary AML cells.

METHODSMononuclear cells were isolated from 27 newly diagnosed AML samples. Apoptosis was analyzed by flow cytometry. IC(50) value of S1 on these samples was determined by XTT assay. The expression level of BCL-2 family members and phosphorylated BCL-2 were assessed by Western blot with subsequent semi-quantitatively densitometric analysis. XTT assay was performed to determine the cell viability of the combined use of S1 and MEK/ERK inhibitor PD98059. The interactions between BCL-2 and pro-apoptosis proteins were tested by co-immunoprecipitation.

RESULTSThe flow-cytometry detection showed that S1 induced the apoptosis of primary AML cells. Based on the responses, 27 primary samples could be classified into three groups: (1) a sensitive group (12 of 27 cases) with IC(50)<14 µmol/L, (2) an intermediate group (8 of 27 cases) with IC(50) of 14-30 µmol/L and (3) a resistant group (7 of 27 cases) with IC(50)>30 µmol/L. The ratio of pBCL-2/(BCL-2+MCL-1) showed a good linear correlation with the IC(50) values. (R(2) = 0.71, P < 0.0001). PD98059 suppressed BCL-2 phosphorylation. When PD98059 suppressed BCL-2 phosphorylation, the apoptotic rate of drug-resistant cells induced by S1 increased from 9.8% to 64.5% (combination index, CI = 0.4), accompanied by more dissociation of BCL-2 heterodimers.

CONCLUSIONThe combination of S1 with PD98059 decrease pBCL-2 level of AML patients and inhibits of the anti-apoptotic function of BCL-2 through enhancing the dissociation of BCL-2 heterodimers.

Antimetabolites, Antineoplastic ; Apoptosis ; Cell Line, Tumor ; Drug Combinations ; Humans ; Leukemia, Myeloid, Acute ; Molecular Mimicry ; Oxonic Acid ; Phosphorylation ; Proto-Oncogene Proteins c-bcl-2 ; Tegafur