OBJECTIVETo investigate the efficiency and safety of different regimens by intravesical instillation of epirubicin, a derivative of adriamycin, for the prevention of primary superficial bladder carcinoma from recurrence.

METHODSNinety patients supplemented with intravesical epirubicin instillation after operation were randomly divided into three groups: Group A--80 mg in one dose; Group B--repeated epirubicin 40 mg q wk x 4-8 sessions followed by q month to the end of the second year; or Group C--50 mg q month to the same duration. All patients were followed up for two years by observing the recurrence rates and side effects.

RESULTSThe recurrence rate of groups A, B and C at one year was 16.7%, 13.3% and 16.7%, respectively, without any significant difference observed. However, it was 50.0%, 36.7% and 36.7% at two years, at which time the recurrence rate of group A was significantly higher than those of groups B and C. The side effects rate was 23.3%, 40.0% and 33.3% for groups A, B and C, respectively. The more instillations the patients had, the more severe side effects were.

CONCLUSIONEarly postoperative single high dose intravesical instillation of epirubicin combined with repeated lower doses of the same drug every month may be an efficient and safe regimen to prevent the primary superficial bladder carcinoma from recurrence.

Administration, Intravesical ; Adult ; Aged ; Antibiotics, Antineoplastic ; administration & dosage ; adverse effects ; Combined Modality Therapy ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; prevention & control ; Postoperative Period ; Prospective Studies ; Urinary Bladder Neoplasms ; prevention & control ; surgery

Animals ; Antibiotics, Antineoplastic ; administration & dosage ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; Hyperthermia, Induced ; methods ; Iodized Oil ; administration & dosage ; Laser Therapy ; Liver Neoplasms, Experimental ; therapy ; Male ; Mitomycin ; administration & dosage ; Neoplasm Transplantation ; Rats ; Rats, Inbred Strains

Antibiotics, Antineoplastic/administration & dosage ; Chemoembolization, Therapeutic ; Combined Modality Therapy ; *Hyperthermia, Induced/methods ; Iodized Oil/administration & dosage ; Laser Therapy ; Liver Neoplasms, Experimental/*therapy ; Mitomycin/administration & dosage ; Neoplasm Transplantation ; Rats, Inbred Strains

PURPOSE: To evaluate the visual outcomes of retinoblastoma in the posterior pole (RBPP) treated with chemotherapy plus local treatments and to address the prognostic factors that influence such outcomes. METHODS: The medical records of patients with RBPP diagnosed at the Department of Pediatric Ophthalmology, Seoul National University Children's Hospital between August 1987 and September 2007 were reviewed retrospectively. Only those patients treated via primary chemotherapy plus local treatments were included. The presence of foveal involvement and tumors in the posterior pole before and after treatment, the type of regression pattern and the best corrected visual acuity (BCVA) of each patient were evaluated. RESULTS: A total of 13 eyes in 12 patients were included. The mean final BCVA for treated RBPP was 20/210 (range, hand motion to 20/16). However, eight eyes (61.5%) had an acuity of 20/200 or better and seven eyes (53.8%) had an acuity of 20/50 or better. The mean final BCVA was significantly better in cases with negative foveal involvement; however, four eyes (37.5%) with positive foveal involvement had an acuity of 20/200 or better. Tumors area in the posterior pole and the type of regression pattern were not significantly related to final BCVA. CONCLUSIONS: Over one half of the studied RBPP patients had working vision. Although the eyes had RBPP with positive foveal involvement, about one-third of the patients had working vision. Vision preservation should be considered when deciding on RBPP treatment.
Antibiotics, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Antineoplastic Agents, Alkylating/administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/*therapeutic use ; Cisplatin/administration & dosage ; Cyclophosphamide/administration & dosage ; Doxorubicin/administration & dosage ; Etoposide/administration & dosage ; Eyeglasses ; Female ; Follow-Up Studies ; Fovea Centralis/pathology ; Humans ; Infant ; Male ; Prognosis ; Retinal Neoplasms/*drug therapy/pathology/*physiopathology ; Retinoblastoma/*drug therapy/pathology/*physiopathology ; Retrospective Studies ; Treatment Outcome ; Visual Acuity

OBJECTIVETo evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment.

METHODSTwenty-nine metastatic TNBC patients were prospectively enrolled to receive capecitabine (1, 000 mg/m(2) twice daily on days 1-14) and cisplatin (75 mg/m(2) on day 1) , repeated every 3 weeks.

RESULTSWith a median of 6 cycles of XP, all 29 patients were evaluable for response, including 18 PR (62.1%), 6 SD (20.7%), 5 PD (17.2%) and no CR. The response rate was 62.1%. Patients with earlier stage at diagnosis (stage I to IIIA), longer post-operative disease free survival (>2 years) and less metastatic sites (≤ 3) obtained significantly higher response rate than patients with later stage at diagnosis (stage IIIB to IV), shorter post-operative disease free survival (≤ 2 years) and more metastatic sites (>3). The leading side effects were grade 1/2 gastrointestinal and hematological toxicities. Grade 3/4 toxicities included neutropenia (34.5%), leukocytopenia (31.0%), anemia (6.9%), thrombocytopenia (3.4%), nausea/vomiting (20.7%), stomatitis (3.4%), and hand-foot syndrome (3.4%).

CONCLUSIONCisplatin and capecitabine combination therapy is an active and well-tolerated doublet treatment in metastatic TNBC patients progressing after anthracycline and taxane treatments.

Anthracyclines ; administration & dosage ; Antibiotics, Antineoplastic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Bridged-Ring Compounds ; administration & dosage ; Capecitabine ; administration & dosage ; adverse effects ; Cisplatin ; administration & dosage ; adverse effects ; Disease-Free Survival ; Female ; Hand-Foot Syndrome ; Humans ; Leukopenia ; chemically induced ; Neutropenia ; chemically induced ; Prospective Studies ; Taxoids ; administration & dosage ; Treatment Outcome ; Triple Negative Breast Neoplasms ; drug therapy ; pathology

This study investigated the effect of TNP-470 in combination with carmustine (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in nude mice. Human glioblastoma U-251 cells (1×10(7)) were injected into 24 nude mice subcutaneously. The tumor-bearing mice were randomly divided into 4 groups on the seventh day following tumor implantation: TNP-470 group, in which TNP-470 was given 30 mg/kg subcutaneously every other day 7 times; BCNU group, in which 20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times; TNP-470 plus BCNU group, in which TNP-470 and BCNU were coadministered in the same manner as in the TNP-470 group and the BCNU group; control group, in which the mice were given 0.2 mL of the mixture including 3% ethanol, 5% acacia and 0.9% saline subcutaneously every other day 7 times. The tumor size and weights were measured. The tumor microvessel density (MVD) was determined by immunostaining by using goat-anti-mouse polyclonal antibody CD105. The results showed that on the 21th day following treatment, the volume of xenografts in the TNP-470 plus BCNU group was (108.93±17.63)mm(3), markedly lower than that in the TNP-470 group [(576.10±114.29)mm(3)] and the BCNU group [(473.01±48.04)mm(3)] (both P<0.01). And the xenograft volume in these 3 treatment groups was even much lower than that in the control group [(1512.61±470.25) mm(3)] (all P<0.01). There was no significant difference in the volume of xenografts between the TNP-470 group and the BCNU group (P>0.05). The inhibition rate of the tumor growth in the TNP-470 plus BCNU group was (92.80±11.37)%, notably higher than that in the TNP-470 group [(61.91±6.29)%] and the BCNU group [(68.73±9.65)%] (both P<0.01) on the 21th day following treatment. There was no significant difference in the inhibition rate of tumor growth between the TNP-470 group and the BCNU group (P>0.05). The MVD of xenografts in the TNP-470 plus BCNU group was decreased significantly as compared with that in the TNP-470 group or the BCNU group (both P<0.05). The MVD of xenografts in the 3 treatment groups was markedly reduced as compared with that in the control group (all P<0.05). No significant changes in weights were observed before and after the treatment in each group (all P>0.05). It was concluded that the combination of TNP-470 and BCNU can significantly inhibit the growth of human glioblastoma xenografts in nude mice without evident side effects.
Angiogenesis Inhibitors ; administration & dosage ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; Antineoplastic Agents, Alkylating ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Brain Neoplasms ; drug therapy ; Carmustine ; administration & dosage ; Cell Line, Tumor ; Cyclohexanes ; administration & dosage ; Female ; Glioblastoma ; drug therapy ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Sesquiterpenes ; administration & dosage ; Xenograft Model Antitumor Assays

BACKGROUND/AIMS: Transarterial chemoembolization (TACE) has long been used as a palliative therapy for unresectable hepatocellular carcinoma (HCC). High-dose hepatic arterial infusion chemotherapy (HAIC) has showed favorable outcomes in patients with intractable, advanced HCC. The aim of this study was to compare the effectiveness and safety of high-dose HAIC and conventional TACE using doxorubicin for advanced HCC. METHODS: The high-dose HAIC group comprised 36 patients who were enrolled prospectively from six institutions. The enrollment criteria were good liver function, main portal vein invasion (including vascular shunt), infiltrative type, bilobar involvement, and/or refractory to prior conventional treatment (TACE, radiofrequency ablation, or percutaneous ethanol injection), and documented progressive disease. Patients received 5-fluorouracil (500 mg/m2 on days 1~3) and cisplatin (60 mg/m2 on day 2 every 4 weeks) via an implantable port system. In the TACE group, 31 patients with characteristics similar to those in the high-dose HAIC group were recruited retrospectively from a single center. Patients underwent a transarterial infusion of doxorubicin every 4~8 weeks. RESULTS: Overall, 6 patients (8.9%) achieved a partial response and 20 patients (29.8%) had stable disease. The objective response rate (complete response+partial response) was significantly better in the high-dose HAIC group than in the TACE group (16.7% vs. 0%, P=0.030). Overall survival was longer in the high-dose HAIC group than in the TACE group (median survival, 193 vs. 119 days; P=0.026). There were no serious adverse effects in the high-dose HAIC group, while hepatic complications occurred more often in the TACE group. CONCLUSIONS: High-dose HAIC appears to improve the tumor response and survival outcome compared to conventional TACE using doxorubicin in patients with intractable, advanced HCC.
Antibiotics, Antineoplastic/*administration & dosage ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage ; Carcinoma, Hepatocellular/drug therapy/mortality/*therapy ; Chemoembolization, Therapeutic ; Cisplatin/administration & dosage ; Doxorubicin/*administration & dosage ; Fluorouracil/administration & dosage ; Humans ; Infusions, Intra-Arterial ; Liver Neoplasms/drug therapy/mortality/*therapy ; Magnetic Resonance Imaging ; Prospective Studies ; Retrospective Studies ; Severity of Illness Index ; Survival Rate ; Tomography, X-Ray Computed

This study is to investigate the inhibitory effect of lidamycin (LDM) and its combination with methotrexate (MTX) on lung metastasis of fibrosarcoma by bioluminescence imaging in athymic mice. A stable luciferase transfected HT-1080 cell line was constructed and the capability to establish experimental lung metastasis in athymic mice was confirmed. The optical imaging system was applied to evaluate the formation of lung metastasis in vivo. In addition, metastatic nodules were counted for the evaluation of inhibition rates. As shown, the fluorescent intensity of luciferase-transfected HT-1080 cells was colinear with the cell population and the minimal detected cell population was 100 cells/well. Optical imaging showed that the fluorescent intensity of treated group was apparently lower than that of the control. The inhibition rates of lung metastasis by LDM alone at 0.025 mg x kg(-1) and 0.05 mg x kg(-1) were 53.9% and 75.9%, respectively, while that of MTX alone at 0.5 mg x kg(-1) was 70.2%. The combination of LDM at 0.025 mg x kg(-1) and MTX at 0.5 mg x kg(-1) showed an inhibition rate of 88.7%. The coefficient of drug interaction (CDI) was 0.82. The results herein demonstrated that LDM alone had strong anti-metastasis effect on human fibrosarcoma HT-1080 and the inhibition efficacy is strengthened when combined with MTX.
Aminoglycosides ; administration & dosage ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; Antimetabolites, Antineoplastic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Cell Line, Tumor ; Drug Synergism ; Enediynes ; administration & dosage ; Female ; Fibrosarcoma ; pathology ; Humans ; Luminescent Measurements ; Lung ; pathology ; Lung Neoplasms ; drug therapy ; pathology ; secondary ; Methotrexate ; administration & dosage ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Random Allocation ; Transfection ; Xenograft Model Antitumor Assays

OBJECTIVE: To assess the technical feasibility and local efficacy of percutaneous radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) for an intermediate-sized (3-5 cm in diameter) hepatocellular carcinoma (HCC) under the dual guidance of biplane fluoroscopy and ultrasonography (US). MATERIALS AND METHODS: Patients with intermediate-sized HCCs were treated with percutaneous RFA combined with TACE. RFA was performed under the dual guidance of biplane fluoroscopy and US within 14 days after TACE. We evaluated the rate of major complications on immediate post-RFA CT images. Primary technique effectiveness rate was determined on one month follow-up CT images. The cumulative rate of local tumor progression was estimated with the use of Kaplan-Meier method. RESULTS: Twenty-one consecutive patients with 21 HCCs (mean size: 3.6 cm; range: 3-4.5 cm) were included. After TACE (mean: 6.7 d; range: 1-14 d), 20 (95.2%) of 21 HCCs were visible on fluoroscopy and were ablated under dual guidance of biplane fluoroscopy and US. The other HCC that was poorly visible by fluoroscopy was ablated under US guidance alone. Major complications were observed in only one patient (pneumothorax). Primary technique effectiveness was achieved for all 21 HCCs in a single RFA session. Cumulative rates of local tumor progression were estimated as 9.5% and 19.0% at one and three years, respectively. CONCLUSION: RFA combined with TACE under dual guidance of biplane fluoroscopy and US is technically feasible and effective for intermediate-sized HCC treatment.
Aged ; Antibiotics, Antineoplastic/administration & dosage ; Antineoplastic Agents/administration & dosage ; Carcinoma, Hepatocellular/*drug therapy/radiography/*surgery/ultrasonography ; Catheter Ablation/*methods ; Chemoembolization, Therapeutic/*methods ; Combined Modality Therapy ; Disease Progression ; Doxorubicin/administration & dosage ; Ethiodized Oil/administration & dosage ; Feasibility Studies ; Female ; Fluoroscopy ; Humans ; Liver Neoplasms/*drug therapy/radiography/*surgery/ultrasonography ; Male ; Postoperative Complications ; *Radiography, Interventional ; Retrospective Studies ; Tomography, X-Ray Computed ; Treatment Outcome ; *Ultrasonography, Interventional

This study is to investigate inhibitory effects of lidamycin (LDM) on the proliferation of HERG K+ channel highly expressing cancer cells and its synergy with anticancer drugs. MTT assay was used to examine the inhibitory effects of lidamycin combined with various anticancer drugs on the proliferation of human lung cancer A549 cells, human colon cancer HT-29 cells and herg-stably-transfected A549 cells. Using the xenograft model of subcutaneously transplanted HT-29 in nude mice, inhibitory effect was appraised in vivo. The coefficient of drug interaction (CDI) was used to evaluate the synergistic effect of drug combination. LDM significantly inhibited the proliferation ofA549 cells and HT-29 cells with IC50 values of 2.14 and 4.64 ng mL(-1), respectively. The efficacy in HT-29 cells with high HERG potassium expression level is less potent than that in A549 cells with low expression level. In terms of IC50 values, LDM suppressed the growth of herg-stably-transfected A549 cells less potently than pCDNA3.1-stably-transfected A549 cells. There existed synergistic effects in the combinations of fluorouracil (5-FU) and LDM, doxorubicin (DOX) and LDM, or hydroxycamptothecine (HCPT) and LDM. CDI values of the combinations of 5-FU and LDM were more than 0.75. CDI values of LDM and DOX were more than 0.70, but some CDI values of LDM and HCPT were less than 0.70. As for the CDI values, synergistic effects of the combination of LDM and HCPT were the most potent of the three groups. There is no relationship between the inhibitory effect of the growth of cancer cells by 5-FU and HERG potassium expression level. HERG expression level negatively correlated with inhibitory effect on the proliferation of cancer cells by DOX. HERG expression levels and chemosensitivity were positively correlated for HCPT. In the model of subcutaneously xenograft transplanted HT-29 in vivo, LDM and/or HCPT effectively inhibited the growth of HT-29 in nude mice, and the optimum CDI of the combination of LDM and HCPT was less than 1. HERG expression level negatively correlates the chemosensitivity of cancer cells to LDM. There exist synergistic effects in vitro and in vivo in the combination of LDM and HCPT, which inhibitory effects of the proliferation of cancer cells positively modulated by HERG potassium expression level. HERG K+ channel may become a target of combined therapy for choosing anticancer drugs.
Aminoglycosides ; administration & dosage ; pharmacology ; Animals ; Antibiotics, Antineoplastic ; administration & dosage ; pharmacology ; Antineoplastic Agents, Phytogenic ; administration & dosage ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Camptothecin ; administration & dosage ; analogs & derivatives ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Doxorubicin ; administration & dosage ; Drug Synergism ; ERG1 Potassium Channel ; Enediynes ; administration & dosage ; pharmacology ; Ether-A-Go-Go Potassium Channels ; metabolism ; Fluorouracil ; administration & dosage ; HT29 Cells ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Xenograft Model Antitumor Assays