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

A 40-year-old female visited our clinic for visual disturbance of the right eye, in which a few creamy-yellow retinal lesions and visual field constrictions were noted. She had been treated for primary CNS lymphoma and was in complete remission. After failure to follow-up for three months, she lost vision in the right eye, at which time active panuveitis was seen. Decreased vision and field constriction was observed in the left eye. Her left eye showed a granular pattern and dye leakage from the vessels and disc on fluorescein angiography and small RPE humps were seen in optical coherence tomography (OCT). Diffuse large malignant B-cells with strong immunoreactivities with CD20 immunostaining were seen in the epiretinal membrane biopsy specimen. Intravitreal injections of methotrexate (MTX) (800 microgram/0.1 ml in the right eye, 400 microgram/0.05 ml in the left eye) were performed twice weekly for one month, once weekly for the following month, once every two weeks for the next month, followed by nine monthly injections. Both eyes were free from malignant cells on vitreous biopsy six months later. There was no leakage seen by angiography, but the granular pattern persisted. Visual field constriction was slightly improved, and the small RPE humpsdetachments seen in OCT disappeared. EOG Arden ratio was decreased in both eyes, and b wave amplitude of scotopic ERG was decreased in the left eye. She was free from recurrence until six months later. No ocular complications except minimal opacity of the crystalline lenses were noted in both eyes.
Adult ; Antimetabolites, Antineoplastic/*administration & dosage ; Drug Administration Schedule ; Eye Neoplasms/*drug therapy ; Female ; Humans ; Injections ; Lymphoma/*drug therapy ; Methotrexate/*administration & dosage ; Treatment Outcome ; Vitreous Body

OBJECTIVETo investigate the efficacy and toxicity of methotrexate (MTX) give intravenously in the primary treatment of gestational trophoblastic tumor (GTT).

METHODSA total of 37 patients with low-risk GTT was primarily treated by single MTX in Women's Hospital, School of Medicine, Zhejiang University. Data on the patients' age, clinical stage, WHO classification criteria, antecedent pregnancy, presenting level of human chorionic gonadotropin, courses of chemotherapy required to achieve complete remission, and toxicity related to chemotherapy treatments were collected.

RESULTSThirty-seven patients with low-risk GTT totally received 137 cycles of MTX between Oct. 1999 and Sep. 2002, 34 patients (91.9%) achieved complete remission. Twenty-nine patients received multiple courses of MTX, complete remission was induced in 26 patients (89.7%). The complete response rates of I stage and III stage were 100.0% and 70.0% (P = 0.03) respectively in patients who were received multiple courses of MTX. However, eight patients received single course of chemotherapy, 7 patients achieved complete remission, and 1 achieved complete remission after another additional course of MTX was conducted. Grade III side effects (WHO criteria) only appeared in 7 courses (5.1%) during MTX treatment. Follow-up data showed that only one patient with single course of chemotherapy relapsed after 6 months.

CONCLUSIONSingle MTX chemotherapy may be effective and well tolerated for low-risk GTT.

Adolescent ; Adult ; Antimetabolites, Antineoplastic ; administration & dosage ; Choriocarcinoma ; drug therapy ; Drug Administration Schedule ; Female ; Gestational Trophoblastic Disease ; drug therapy ; Humans ; Methotrexate ; administration & dosage ; Pregnancy ; Uterine Neoplasms ; drug therapy

This study evaluated the effects of electric pulses combined with antitumor drugs on S180 tumor cells. It was found that the growth of S180 sarcoma was inhibited with a maximum inhibition ratio of 95.5% after the use of electric pulses in combination with the injection of bleomycin (BLM), and the blood vessels of tumor were obviously fewer than those of the untreated tumor in vivo. The mitochondria of S180 tumor cells were swollen after the use of electric pulses in combination with adriamycin. The results showed that electrochemotherapy has evident inhibitory effect on the growth of S180 sarcoma and the mechanism may involve the suppression of tumor angiogenesis and changes in the ultrastructures of tumor cells.
Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; Bleomycin ; administration & dosage ; Combined Modality Therapy ; Electric Stimulation Therapy ; methods ; Electrochemistry ; Mice ; Neovascularization, Pathologic ; prevention & control ; Sarcoma 180 ; blood supply ; therapy

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

OBJECTIVETo investigate the postoperative adverse events and survival of patients with sustained-released fluorouracil implanted during operation.

METHODSData of 124 patients with advanced gastric cancer undergoing radical operation in Tianjin Medical University Cancer Institute and Hospital from January 2007 to January 2009 were analyzed retrospectively. All the patients were divided into two groups according to whether intra-operative fluorouracil was implanted or not. The treatment group(n=64) was implanted with fluorouracil in abdominal cavity after radical resection. The control group(n=60) did not receive fluorouracil implant in abdominal cavity after radical resection. Abdominal drainage fluid, temperature and adverse events within 15 postoperative days and 3-year survival were observed and compared between the two groups.

RESULTSPathological findings of the two groups were similar. No statistical significances existed in abdominal drainage fluid, temperature and adverse events within 15 postoperative days(P>0.05). The 3-year survival rate was higher in treatment group(64.3% vs. 42.4%, P=0.018).

CONCLUSIONIntra-operative sustained-released fluorouracil implants are safe and tolerable, and can improve the survival rate of patients with advanced gastric cancer.

Abdominal Cavity ; Antimetabolites, Antineoplastic ; administration & dosage ; therapeutic use ; Fluorouracil ; administration & dosage ; therapeutic use ; Humans ; Retrospective Studies ; Stomach Neoplasms ; drug therapy ; surgery ; Survival Rate

OBJECTIVETo study the antitumor effect of peri-tumor implantation of delayed-release 5-fluorouracil implants on xenograft colorectal tumor in mice.

METHODSFifty tumor-bearing nude mice were randomly divided into 5 groups. Group A and B were treated with peri-tumor implantation of 5-fluorouracil implants and the dose of 5-fluorouracil was 200 and 100 mg/kg, respectively. Group C and D were treated with peri-tumor injection of 5-fluorouracil solution and the dose of 5-fluorouracil was 200 and 100 mg/kg, respectively. Group E did not receive any treatment. A growth curve was plotted for changes in tumor volume, the weight of the tumor was measured and tumor inhibition rate was calculated.

RESULTSThe growth curve was mild in group A and B and steep in group C, D and E. There were statistical differences in tumor volume between groups A and B and other groups and there were no statistical differences in tumor volume among group C, D and E. After 12 days, tumor inhibition rate was 72% in group A, 51% in group B, 8% in group C, and 5% in group C. There were statistical differences in inhibition rate between group A, B and C, D (P<0.05). The weight changes before and after the treatment among the 5 groups were not statistically different. During the study, 1 mouse in group A died, 4 in group C and 1 in group D.

CONCLUSIONDelayed-release 5-fluorouracil implants can effectively inhibit tumor growth.

Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; Colorectal Neoplasms ; drug therapy ; Delayed-Action Preparations ; Female ; Fluorouracil ; administration & dosage ; Male ; Mice ; Mice, Nude ; Xenograft Model Antitumor Assays

In this study we prepared mitoxantrone-insulin conjugate wherein mitoxantrone was an anticancer model drug and insulin acted as its vector leading to tumor cells. The drug loading of the conjugate was determined to be 11.68%. Stability trials of the conjugate were carried out in different pH buffer solutions and mouse plasma under 37 degrees C which showed the stability of the conjugate in vitro. Lyophilized powder was prepared and its pharmaceutical qualities were assessed. The retained biological activity of the insulin within the conjugate, demonstrated by animal experiments.
Animals ; Antimetabolites, Antineoplastic ; administration & dosage ; chemistry ; Drug Carriers ; Drug Delivery Systems ; Drug Stability ; Insulin ; chemistry ; Mice ; Mitoxantrone ; administration & dosage ; chemistry ; Neoplasms ; drug therapy ; Powders

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

OBJECTIVEPrimary to search the rule of pre-operative chemotherapy and suitable duration for it by investigating the changes of calpain content and activity after 5'-deoxy-5-fluorouridine (5'-DFUR) per oral administered pre-operatively in different time. Further to investigate the mechanism of chemotherapy.

METHODSSeventy-three patients with gastrointestinal malignant tumors were divided into 4 groups by the time of 5'-DFUR (600 approximately 1200 mg/d) by oral administration before operation, group A, 3 days, 27 cases; group B, 1 week, 22 cases; group C, 2 weeks, 15 cases; group D, 2 months, 9 cases. And group E, control group, had 24 patients with gastrointestinal malignant tumors at the same term. The patients above all had not received the other chemotherapy and radiotherapy. Western blot and immunoelectron microscopy were employed to detect the expressing levels and activities of calpain in tumor tissues of different groups.

RESULTSElectronic microscopic examination showed gold granula mainly on the membranes of mitochondria of tumor cells to groups after chemotherapy. And the tumor cells of group A were mildly damaged. Besides that, serious injury for tumor cells of group B could be seen, and the phenomena were common in group C. But the damages to tumor cells of group D were mainly about mildness. The results of immunoelectron microscopy revealed that the contents of calpain increased following the time of chemotherapy prolonging, and peaked in group C. Still more, there was no significant difference for the results between group C and group D. The changes of calpain activities observed by western blot had the same tendency as the results from immunoelectron microscopy (r = 0.86, P < 0.0001).

CONCLUSIONS5'-DFUR via oral administered pre-operation could have anti-cancer effect through calpain. And the effect might be strongest in 2 weeks also after chemotherapy.

Administration, Oral ; Adult ; Aged ; Antimetabolites, Antineoplastic ; therapeutic use ; Calpain ; metabolism ; Chemotherapy, Adjuvant ; Female ; Floxuridine ; therapeutic use ; Gastrointestinal Neoplasms ; drug therapy ; enzymology ; ultrastructure ; Humans ; Male ; Middle Aged ; Time Factors