No abstract available.
Administration, Intravenous* ; Cervix Uteri* ; Cisplatin* ; Female ; Fluorouracil*

The aim of this work was to investigate guar gum/ethylcellulose mix coated pellets for potential colon-specific drug delivery. The coated pellets, containing 5-fluorouracil as a model drug, were prepared in a fluidized bed coater by spraying the aqueous/ethanol dispersion mixture of guar gum and ethylcellulose. The lag time of drug release and release rate were adjustable by changing the ratio of guar gum to ethylcellulose and coat weight gain. In order to find the optimal coating formulation that was able to achieve drug targeting to the colon, the effect of two independent variables (the ratio of guar gum to ethylcellulose and the coat weight gain) on drug release characteristics was studied using 3 x 4 factorial design and response surface methodology. Results indicated that drug release rate decreased as the proportion of ethylcellulose in the hybrid coat and the coat weight gain increased. When the ratio of guar gum to ethylcellulose was kept in the range of 0.2 to 0.7, and the coat weight gain in the range of 250% to 500%, the coated pellets can keep intact for about 5 h in upper gastrointestine and achieve colon-specific drug delivery. The pellets prepared under optimal conditions resulted in delayed-release sigmoidal patterns with T(5%) (time for 5% drug release) of 5.1 - 7.8 h and T(90%) (time for 90% drug release) of 9.8 - 16.3 h. Further more, drug release was accelerated and T(90%) of the optimum formulation pellets decreased to 9.0 - 14.5 h in pH 6.5 phosphate buffer with hydrolase. It is concluded that mixed coating of guar gum and ethylcellulose is able to provide protection of the drug load in the upper gastrointestinal tract, while allowing enzymatic breakdown of the hybrid coat to release the drug load in the colon.
Cellulose ; administration & dosage ; analogs & derivatives ; Colon ; metabolism ; Drug Delivery Systems ; Fluorouracil ; administration & dosage ; chemistry ; Galactans ; administration & dosage ; Mannans ; administration & dosage ; Plant Gums ; administration & dosage

OBJECTIVETo investigate the level of occupational exposure to 5-fluorouracil (5-Fu) in the pharmacy intravenous admixture service (PIVAS) of a hospital, and identify the sources of 5-Fu contamination.

METHODSThe 5-Fu concentrations in air, on the surface of different areas in PIVAS and personal protective equipments were detected using UV-vis spectrophotometry.

RESULTSThe 5-Fu in air could not be detected. The 5-Fu concentrations on five different surfaces of biological safety cabinets were (22.00 +/- 6.35), (13.99 +/- 2.46), (14.13 +/- 0.72), (7.25 +/- 1.19) and (9.87 +/- 1.23) ng/cm2, respectively, which were significantly higher than those [(3.14 +/- 0.04), (5.43 +/- 0.65), (2.26 +/- 0.17), (2.26 +/- 0.17) and (3.63 +/- 0.46) ng/cm2] of corresponding controls (P < 0.05 or P < 0.01). The 5-Fu concentrations of the floor under cabinets [(18.19 +/- 5.22) ng/cm2], the floor in front of cabinets [(10.25 +/- 2.57)ng/cm2], the office floor [(11.64 +/- 2.53) ng/cm2], the terrace floor [(99.89 +/- 14.06 ) ng/cm2], the floor beside trash can in dressing room [(24.54 +/- 0.23) ng/cm2] were significantly higher than those of control [(3.36 +/- 0.11 ) ng/cm2] (P < 0.05 or P < 0.01). The 5-Fu concentrations of the tables in preparation room [(7.22 +/- l.04) ng/cm2] and the tables in office [(11.81 +/- 1.18) ng/cm2] were significantly higher than those of control [(5.56 +/- 0.14) ng/cm2] (P < 0.05 or P < 0.01). The 5-Fu concentrations of the indoor handle in preparation room were significantly higher than those of controls (P < 0.05 or P < 0.01). 5-Fu concentrations on the surfaces of outdoor handle and floor beside door in preparation room were not significantly increased compared with controls (P > 0.05). The 5-Fu concentrations on the surfaces of infusion bags, transfer box, transfer trays were significantly higher than those of controls (P < 0.05). The differences of 5-Fu concentrations between outer and inner masks and controls were not significant (P > 0.05). The 5-Fu concentrations of gloves of preparing and checking staffs were significantly higher than those of controls (P < 0.05 or P < 0.01).

CONCLUSIONThe preparing and checking process of 5-Fu and the treatment of medical wastes are major sources of 5-Fu contamination.

Antineoplastic Agents ; analysis ; Drug Administration Routes ; Fluorouracil ; analysis ; Humans ; Occupational Exposure ; Pharmacy Service, Hospital

This study was to determine which of two routes of administration of 5-fluorouracil (5-FU) is more effective, by measuring the radioactvity in the body tissues of gastric cancer patients after the administration of 5-FU-l4C via the systemic intravenous and the regional intra-arterial routes. After the drug was administered intravenously in one group of patients, and intra-arterially in another; samples of portal venous blood, the liver, the lymph nodes, and the normal and the cancerous tissues of the stomach were obtained. The radioactivities of the samples were measured, and it was found that those of the regional lymph nodes, the liver, and the normal and the cancerous tissues of the stomach were much higher in the latter group. The regional intra-arterial routes is the more effective way to administer 5-FU in patients with stomach cancer.
Carbon Radioisotopes/diagnostic use ; Comparative Study ; Fluorouracil/administration & dosage ; Fluorouracil/metabolism* ; Human ; Injections, Intra-Arterial ; Injections, Intravenous ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/metabolism

BACKGROUNDNasopharyngeal carcinoma (NPC) is a squamous-cell carcinoma especially prevailing among the natives of southern China. The regimen of concurrent chemoradiotherapy (CCRT) that include platinum and 5-fluorouracil (5-FU) is considered to be the standard treatment for NPC. However, its clinical use is limited by its toxicity. Our purpose was to evaluate the efficacy and safety of the regimen of CCRT with taxanes and platinum versus the regimen of CCRT with 5-FU and platinum in NPC treatment.

METHODSMedline, the Cochrane library, and the Chinese medical literature database were searched for eligible studies. Meta-analysis was performed using Review Manager (Version 5.2).

RESULTSSix random controlled trials (RCTs) including 514 patients met our criteria. Meta-analysis showed that the regimen of CCRT with taxanes and platinum had an improved significant difference in complete remission (CR) and less incidence rate in adverse reactions such as gastrointestinal impairment grades III-IV, liver and kidney impairment grades I-II, and radiodermatitis grades III-IV versus the conventional regimen of CCRT with 5-FU and platinum, while the longterm effectiveness rate of overall survival, locoregional failure-free survival, or distant metastasis failure-free survival between the two groups was therapeutic equivalence.

CONCLUSIONSThe regimen of CCRT with taxanes and platinum in NPC therapy may be more efficient and safe compared to the conventional modality of 5-FU and platinum in CCRT. However, we need more high-quality studies of multi-center and randomized double-blind clinical trials to further compare, analyze, and confirm the findings.

Carcinoma ; Chemoradiotherapy ; Fluorouracil ; administration & dosage ; therapeutic use ; Humans ; Nasopharyngeal Neoplasms ; drug therapy ; Platinum ; administration & dosage ; therapeutic use ; Taxoids ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVETo evaluate the effects and safety of OXA-LV5FU2 regimen for patients with advanced/metastatic gastric cancer.

METHODSOXA 100 mg/m(2) i.v. 2hr d1, LV200 mg/m(2) i.v. 2hr followed by 5-Fu 400 mg/m(2) i.v. bolus and 5-Fu 600 mg/m(2) i.v. 22hr d1, 2 were given, and repeated every 2 weeks. Efficacy was evaluated at 4 cycles (8 weeks).

RESULTSForty three patients have been entered into the study. Patients with primary tumor resected or non-resected were 17 and 26. The evaluable lesions were 26 primary lesions, 22 lymph node metastases, 12 liver metastases, 1 pancreas metastasis and 2 soft tissue metastases. Forty patients were evaluable for clinical response. Four patients achieved CR (10.0%), 13 PR (32.5%), ORR 42.5% (95% CI 27.2 - 57.8), 17 SD (42.5%) and 6 PD (15.0%). Overall response rate (ORR) for chemotherapy naive (1(st) line) and pretreated (2(nd) line) patients were 50.0% (14/28) and 25.0% (3/12), respectively. Median time to progress (mTTP) was 5 months and median overall survival (mOS) was 8 months. Forty-three patients were evaluable for toxicity, with Grade 3, 4 WHO toxicity of neutropenia in 7 patients (16.3%), thrombocytopenia in 3 patients (7.0%), nausea/vomiting in 1 patient (2.3%). There were no Grade 3, 4 peripheral neuropathy toxicity or any deaths during treatment.

CONCLUSIONOXA-LV5FU2 is a high response regimen for advanced gastric cancer with mild toxicity, which can be practiced safely.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Female ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Male ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; Stomach Neoplasms ; drug therapy

OBJECTIVETo evaluate the clinical efficacy of capecitabine combined with transcatheter arterial chemoembolization (TACE) for advanced liver cancer.

METHODSForty-nine patients with liver cancer were retrospectively divided into two groups: Treatment group, on the basis of TACE, 23 patients received oral capecitabine at 2500 mg/m(2), twice-daily for 14 days followed by 7-day rest period and repeated in every three week intervals for more than two cycles. Control group, 26 patients received TACE only at 2-month intervals for at least two cycles.

RESULTSIn capecitabine and TACE group: there were 1 CR, 14 PR, 5 SD and 3 PD; the overall response rate was 65.2%; the AFP and tumor reduction rates were 68.8% and 73.9%; the median survival time was 11.9 months. In the TACE only group: there were 0 CR, 7 PR, 12 SD and 7 PD; the overall response rate was 26.9%; the AFP and tumor reduction rates were 31.6 % and 30.8%; the median survival time was 8.3 months. The most common side-effects of capecitabine were hand-foot syndrome and diarrhea.

CONCLUSIONCapecitabine combined with TACE is safe and effective for advanced liver cancer.

Administration, Oral ; Adult ; Aged ; Antimetabolites, Antineoplastic ; administration & dosage ; Capecitabine ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Deoxycytidine ; administration & dosage ; analogs & derivatives ; Drug Administration Schedule ; Female ; Fluorouracil ; analogs & derivatives ; Humans ; Liver Neoplasms ; pathology ; therapy ; Male ; Middle Aged ; Mitomycin ; administration & dosage

No abstract available.
Adult ; Aged ; Antineoplastic Agents/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; Benzenesulfonates/administration & dosage ; Carcinoma, Hepatocellular/mortality/*therapy ; Chemoembolization, Therapeutic ; Cisplatin/administration & dosage ; Fluorouracil/administration & dosage ; Humans ; Infusions, Intra-Arterial ; Liver Neoplasms/mortality/*therapy ; Middle Aged ; Pyridines/administration & dosage ; Survival Rate

BACKGROUNDA phase III trial involving docetaxel, cisplatin, and fluorouracil (DCF) in the treatment of advanced gastric cancer was shown to have superior efficacy compared to cisplatin and fluorouracil alone, but with a high rate of hematologic toxicity. To reduce toxicity while maintaining the efficacy of DCF, we reduced the doses of docetaxel (D) and cis-platinum (CDDP), and administered 5-fluorouracil (5-FU) via a continuous intravenous (CIV) infusion.

METHODSChemotherapy-naive patients with gastric adenocarcinomas received D (60 mg/m(2) 1 hour on day 1), CDDP (30 mg/m(2) on days 1 and 2), and 5-FU (1500 mg×m(-2)×24 h(-1) CIV on days 1 and 8 every 3 weeks). The primary endpoint was the response rate.

RESULTSFourteen patients were enrolled. Based on the efficacy evaluation following at least 2 cycles of treatment, there was 7.1% complete remission (CR), 71% partial remission (PR), 14% stable disease (NC/SD), and 7.1% progressive disease (PD). The median survival time was 13 months. Nine patients (64%) had grade III-IV neutropenia, and 4 patients (29%) had grade IV neutropenia, among whom 1 had grade IV neutropenia with grade III nausea and vomiting.

CONCLUSIONThe modified DCF regimen is highly active and has a favorable toxicity profile in Chinese patients with gastric cancer.

Adenocarcinoma ; drug therapy ; Antimetabolites, Antineoplastic ; administration & dosage ; Antineoplastic Agents ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cisplatin ; administration & dosage ; Female ; Fluorouracil ; administration & dosage ; Humans ; Male ; Middle Aged ; Stomach Neoplasms ; drug therapy ; Taxoids ; administration & dosage

OBJECTIVETo evaluate the safety and preliminary efficacy of dose-modified regimen of 5-fluorouracil plus oxaliplatin and irinotecan (mFOLFOXIRI) for patients with advanced colorectal cancer (CRC).

METHODSData of 312 CRC patients confirmed by pathology receiving triplet drug alone or combined with target therapy between October 2012 and December 2016 at the Sixth Affiliated Hospital of Sun Yat-sen University were retrospectively analyzed. CRC patients who had previously completed adjuvant therapy (or neoadjuvant therapy) within 6 months or palliative chemotherapy were excluded, meanwhile those with poor general condition (ECOG score > 2) or grade 2 neuropathy and allergy to oxaliplatin were excluded as well. Regimen of mFOLFOXIRI: oxaliplatin 85 mg/m² dissolved in 5% glucose solution 500 ml by intravenous infusion for 2 h; irinotecan 150 to 165 mg/m² dissolved in 0.9% sodium chloride 250 ml by intravenous infusion for 90 min; following intravenous infusion of leucovorin 400 mg/m² for 2 h, day 1; 5-FU 2800 mg/m², 48-h continuous intravenous infusion; once every 2 weeks. Therapy could be combined with a targeted drug, bevacizumab 5 mg/kg every two weeks; cetuximab 500 mg/m² every two weeks. Side effect was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE 4.0.3). The objective response rate was evaluated according to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1) after administering at least four cycles of chemotherapy.

RESULTSThe median age was 52 years (range 16-73) in the whole group; 113 patients (36.2%) had locally advanced CRC, and 199 (63.8%) had metastatic CRC. Most patients (274/312, 87.8%) did not receive any treatment earlier. There were a total of 1651 chemotherapy cycles in the whole group, with a median of 6(1-19) cycles. Of these 1651 cycles, 124 cycles of chemotherapy(7.5%) were dose-adjusted; 176 cycles of chemotherapy(10.7%) were delayed for median 5(3-13) days; 124 cycles(7.5%) required dose decrease. The overall relative dose intensity was >90%; the specific drug dose intensity was 93.6%(2620 mg×m⁻²×d⁻¹) for fluorouracil, 97.8%(83 mg×m⁻²×d⁻¹) for oxaliplatin, and 94.2%(155 mg×m⁻²×d⁻¹) for irinotecan. Twenty-three patients (7 of intestinal perforation, 7 of intestinal obstruction, 1 of grade 4 hematologic toxicity, and 8 of grade 3 fatigue) refused subsequent chemotherapy due to intolerable toxicity. Main grade 3 or 4 adverse events in patients were neutropenia in 69 cases (22.1%), fatigue in 35 cases (11.2%), and anemia in 28 cases (8.9%). Twenty serious adverse events (6.4%) occurred, including 13 patients of febrile neutropenia (4.2%), 7 patients of intestinal perforation (2.2%, 4 patients in upper rectum, 2 in sigmoid colon, and 1 in transverse colon cancer), and 9 of them had subsequent sepsis (2.9%). All the patients with intestinal perforation underwent emergency operation. No treatment-related deaths occurred. In 199 patients with metastatic CRC, because 22 patients did not receive image evaluation, the preliminary efficacy of 177 patients was actually evaluated. A total of 113 objective response events were observed. The overall response rate was 63.8%(113/177), partial response rate was 61.6%(109/177), clinically complete response rate was 2.3%(4/177), stable disease was 29.9% (53/177), progressive disease was 6.2%(11/177), and the disease control rate was 93.8%(166/177). In 127 patients receiving triplet drug, objective response rate was 40.9% for those with less than four cycles and 81.1% for those with more than four cycles (P<0.001).

CONCLUSIONThe mFOLFOXIRI regimen with reduced dose can be safely used in advanced CRC and has achieved promising results in terms of short-term efficacy.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; therapeutic use ; Camptothecin ; administration & dosage ; analogs & derivatives ; Colorectal Neoplasms ; drug therapy ; Fluorouracil ; administration & dosage ; Humans ; Leucovorin ; administration & dosage ; Middle Aged ; Organoplatinum Compounds ; administration & dosage ; Retrospective Studies ; Treatment Outcome ; Young Adult