OBJECTIVE: To investigate the association between single nucleotide polymorphism of NUDT15 gene (SNP rs116855232) and hepatotoxicity in children with acute lymphocytic leukemia (ALL). METHODS: A total of 135 children with ALL in Shandong Province were recruited in this study, and patients were divided into two groups based on the presence of liver injury. Genotypes of each patient were detected using PCR and Sanger sequencing. Clinical data and the average dose of 6-mercaptopurine (6-MP) were collected and analyzed by SPSS 19.0 software. RESULTS: Respectively, 99 patients were found with CC genotype, 32 patients with CT genotype and 4 patients with TT genotype. Compared with ALL patients without hepatotoxicity, there was a difference in genotypes between the two groups in the initial stage of chemotherapy for leukemia (Chi CONCLUSION The polymorphism of rs116855232 in NUDT15 gene was associated with hepatotoxicity induced by 6-mercaptopurine in children with ALL, and ALL patients with TT genotype should take a lower dose of 6-MP to avoided hepatotoxicity.
Antimetabolites, Antineoplastic/therapeutic use* ; Chemical and Drug Induced Liver Injury/genetics* ; Child ; Genotype ; Humans ; Mercaptopurine/adverse effects* ; Polymorphism, Single Nucleotide ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics* ; Pyrophosphatases/genetics*

The role of neoadjuvant chemoradiation therapy in locally advanced pancreatic cancer (LAPC) is still controversial. The aim of this study was to evaluate surgical downstaging after concurrent chemoradiation therapy (CCRT) for LAPC by measuring the objective changes after treatment. From January 2003 through July 2011, 54 patients with LAPC underwent neoadjuvant CCRT. Computed tomography findings of the tumor size, including major vessel invasion, were analyzed before and after CCRT. Among the total recruited patients, 14 had borderline resectable malignancy and another 40 were unresectable before CCRT. After CCRT, a partial response was achieved in four patients. Stable disease and further disease progression were achieved in 36 and 14 patients, respectively. Tumor size showed no significant difference before and after CCRT (3.6 +/- 1.1 vs. 3.6 +/- 1.0 cm, P = 0.61). Vessel invasion showed improvement in two patients, while 13 other patients showed further tumor progression. Thirty-nine patients with unresectable malignancy and 11 patients with borderline resectable malignancy at time of initial diagnosis remained unchanged after CCRT. Four patients with borderline pancreatic malignancy progressed to an unresectable stage, whereas one unresectable pancreatic malignancy improved to a borderline resectable stage. Only one patient with borderline resectable disease underwent operation after CCRT; however, curative resection failed due to celiac artery invasion and peritoneal seeding. The adverse events associated with CCRT were tolerable. In conclusion, preoperative CCRT in LAPC rarely leads to surgical downstaging, and it could lower resectability rates.
Adenocarcinoma/radiography/therapy ; Adult ; Aged ; Aged, 80 and over ; Antimetabolites, Antineoplastic/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Capecitabine/therapeutic use ; Carcinoma, Pancreatic Ductal/*radiography/*therapy ; Chemoradiotherapy/adverse effects/*methods ; Combined Modality Therapy ; Deoxycytidine/analogs & derivatives/therapeutic use ; Disease Progression ; Female ; Fluorouracil/therapeutic use ; Humans ; Male ; Middle Aged ; Neoadjuvant Therapy ; Neoplasm Staging ; Pancreas/blood supply/pathology ; Pancreatic Neoplasms/*radiography/*therapy ; Retrospective Studies ; Treatment Outcome

Treating patients undergoing chemotherapy who display findings of liver toxicity, requires a solid understanding of these medications. It is important for any clinician to have an index of suspicion for liver toxicity and be able to recognize it, even on imaging. Cancer chemotherapy has evolved, and newer medications that target cell biology have a different pattern of liver toxicity and may differ from the more traditional cytotoxic agents. There are several hepatic conditions that can result and keen clinical as well as radiographic recognition are paramount. Conditions such as sinusoidal obstructive syndrome, steatosis, and pseudocirrhosis are more commonly associated with chemotherapy. These conditions can display clinical signs of acute hepatitis, liver cirrhosis, and even liver failure. It is important to anticipate and recognize these adverse reactions and thus appropriate clinical action can be taken. Often times, patients with these liver manifestations can be managed with supportive therapies, and liver toxicity may resolve after discontinuation of chemotherapy.
Adult ; Aged ; Antibiotics, Antineoplastic/adverse effects/therapeutic use ; Antimetabolites, Antineoplastic/adverse effects/therapeutic use ; Antineoplastic Agents/*adverse effects/therapeutic use ; Antineoplastic Agents, Alkylating/adverse effects/therapeutic use ; Drug-Induced Liver Injury/etiology/radiography ; Enzyme Inhibitors/adverse effects/therapeutic use ; Fatty Liver/etiology/radiography ; Female ; Humans ; Immunotherapy ; Liver Cirrhosis/etiology/radiography ; Liver Diseases/etiology/*radiography ; Male ; Middle Aged ; Neoplasms/therapy ; Tomography, X-Ray Computed

No abstract available.
Adult ; Antimetabolites, Antineoplastic/*adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Biopsy ; Bone Marrow Examination ; Chemotherapy, Adjuvant ; Colectomy ; Colorectal Neoplasms/*drug therapy/pathology/surgery ; Cytogenetic Analysis ; Fluorouracil/*adverse effects ; Humans ; Leukemia, Myeloid, Acute/*chemically induced/diagnosis/drug therapy ; Male ; Treatment Outcome

Acute Disease ; Antimetabolites, Antineoplastic ; adverse effects ; toxicity ; Drug-Related Side Effects and Adverse Reactions ; Female ; Folic Acid Antagonists ; therapeutic use ; Humans ; Methotrexate ; adverse effects ; toxicity ; Middle Aged ; Nausea ; chemically induced ; Risk Factors ; Skin Diseases ; chemically induced ; Vomiting ; chemically induced

This study was purposed to investigate the effects of high-dose methotrexate (HD-MTX)-CF + VDT protocol on pediatric acute lymphoblastic leukemia (ALL) by means of retrospective analysis. MTX plasma concentration was dynamically detected and evaluated so as to avoid or reduce the side effects of HD-MTX, and adjust the time and dosage of calcium folinate (CF) or carry out the plasma exchange as occasion requires. Totally 180 cases of ALL were enrolled in this study, and received 380 administration of HD-MTX-CF + VDT protocol, including 122 patients with induction therapy as well as 58 cases during maintenance therapy, among which 68 cases were defined as low risk, 80 cases as middle risk and 32 cases as high risk. 2.0 g/m(2) MTX, 3.0 g/m(2) MTX, and 5.0 g/m(2) MTX were individually used according to low risk, middle risk or T immunohistochemical expression. The results indicated that 36.3% cases showed the side-effects of HD-MTX including mucocutaneous lesions, gastrointestinal reaction, hepatic dysfunction, renal damage, fever, myelosuppression, cardiotoxicity, infection and allergic response. All of these side effects were reversible through treatment. The elimination delay of MTX occurred in 110 cases, out of which 3 cases got MTX concentration > 10 µmol/L at 24 hours, 50 cases > 1.0 µmol/L at 44 hours, the remaining 57 cases > 0.1 µmol/L at 68 hours. CF dosage was adjusted according to the concentration of MTX until it was less than 0.1 µmol/L. 1 case had renal interstitial inflammation and acute renal failure, but finally he was cured. No patients received plasma exchange or died. It is concluded that the extramedullary leukemia control protocol, in which MTX is main drug, is effective therapy for obtaining long-term remission and event-free survival rate in ALL patients, but the side effects and risks increase along with the increase of MTX dose. The metabolic level of HD-MTX has found to be obvious individual, so the dynamic monitoring of MTX concentration in plasma and administration of proper dosage of CF are important factors for HD-MTX protocol application in ALL patients.
Adolescent ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Methotrexate ; administration & dosage ; adverse effects ; blood ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; blood ; drug therapy

OBJECTIVETo evaluate the efficacy and safety of intravesical instillation with gemcitabine after first-line intravesical chemotherapy failure, including mitomycin (MMC), epirubicin (EPB) and camptothecin (CPT), in the treatment of non-muscle-invasive bladder cancer (NMIBC).

METHODSFrom June 2007 to October 2008, 72 patients with NMIBC, who had tumor recurrence within one year of first-line intravesical chemotherapy, were assigned to 3 groups (24 cases each). Group A received intravesical gemcitabine in a dose of 1000 mg, Group B received 2000 mg gemcitabine, and Group C received original intravesical chemotherapy. The time of reccurrence and adverse effects were recorded.

RESULTSThe 2-year tumor free survival rates of the 3 groups were 66.7%, 75.0% and 45.8%, respectively. The 2-year TFS rate of the patients who received gemcitabine was 70.8%, significantly higher than 45.8% of the patients treated by original chemotherapy. There was one case with renal function impairement in the groups A and B, respectively. There was no significant difference between the rates of low urinary tract symptoms in the 3 groups. No severe hematological side effects were observed in this study.

CONCLUSIONThe intravescal chemotherapy with gemcitabine in patients with recurrent bladder tumor after first-line intravesical chemotherapy is effective and well tolerated, however, renal function should be routinely assessed.

Administration, Intravesical ; Adult ; Aged ; Antibiotics, Antineoplastic ; therapeutic use ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Camptothecin ; therapeutic use ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Disease-Free Survival ; Dose-Response Relationship, Drug ; Epirubicin ; therapeutic use ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Mitomycin ; therapeutic use ; Neoplasm Invasiveness ; Neoplasm Recurrence, Local ; Urinary Bladder Neoplasms ; drug therapy ; pathology

OBJECTIVETo observe the local control rate, survival time and side effect of three-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma.

METHODSForty patients with postoperative recurrent rectal carcinoma received three-dimensional conformal radiation therapy, 1.8 - 2.0 Gy/once, 5 times every week and the total dose was 54 - 65 Gy. At the same time, the patients took Tegafur orally 40 mg/m(2) twice per day for consecutive 28 days, and one cycle lasted for 42 days. The chemotherapy was applied for 2 cycles after radiotherapy.

RESULTSThe total effective rate (CR + PR) was 70.0%, improvement rate was 90.0%, 1-year survival rate was 70.0%, and 1-year local control rate was 62.5%. There was only a little side effect.

CONCLUSIONSThree-dimensional conformal radiation therapy combined with Tegafur for postoperative recurrent rectal carcinoma have definite effect, with a high local control rate, and patients well tolerance the treatment without serious side effect. It can apparently improve the life quality of the patients.

Adenocarcinoma ; drug therapy ; radiotherapy ; surgery ; Adult ; Aged ; Antimetabolites, Antineoplastic ; adverse effects ; therapeutic use ; Combined Modality Therapy ; Diarrhea ; etiology ; Exanthema ; chemically induced ; etiology ; Female ; Humans ; Leukopenia ; etiology ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Postoperative Period ; Quality of Life ; Radiotherapy, Conformal ; adverse effects ; Rectal Neoplasms ; drug therapy ; radiotherapy ; surgery ; Remission Induction ; Survival Rate ; Tegafur ; adverse effects ; therapeutic use

OBJECTIVETo evaluate the efficacy of late accelerated hyperfractionated conformal radiotherapy (LACF) combined with capecitabine on esophageal carcinoma.

METHODSOne hundred and sixty eight patients of esophageal cancer were randomly divided into 3 groups, including the radiotherapy alone group (CF) which received conventional conformal radiotherapy to a total of 60 - 66 Gy, LCAF group which received conventional fractionated conformal radiotherapy during the first two-thirds of the treatment to a dose about 40 Gy/20F/4W, then followed by late accelerated hyperfractionated conformal radiotherapy, twice daily radiotherapy at 1.3 Gy per fraction to a total dose about 64 - 69 Gy, and LCAF + C group (late accelerated hyperfractionated radiotherapy combined with capecitabine), in which patients were treated as the same as the LCAF group, except that they were treated with capecitabine (1.5 g po bid) from beginning of the radiotherapy to the end.

RESULTSThe short-term results of the 3 groups were 74.0%, 85.5% and 95.2%, respectively (P = 0.006). The local control rates at 1, 3 and 5 years were 64.0%, 30.0%, 24.0% in the CF group, 81.8%, 65.5%, 58.2% in the LCAF group and 90.1%, 77.8%, 74.6% in the LCAF+C group, respectively. The 1-, 3- and 5-year survival rates of the 3 groups were 58.0%, 20.0%, 8.0%; 78.2%, 36.4%, 17.0% and 85.7%, 55.6%, 30.2%, respectively. The effect of LCAF+C group was better than that of LCAF group and CF group. The incidence of acute tracheitis and acute esophagitis in the LCAF+C group and LCAF group was higher than that in the CF group, but there was no stastistically significant difference between the 2 groups. There was no statistically significant difference in distant metastasis in the 3 groups.

CONCLUSIONSCapecitabine, as an effective chemosensitizater combined with late accelerate hyperfractionated radiotherapy can improve the short-term results of treatment of esophageal cancer. The value of this combined treatment in distant metastasis reqires further study in the clinic.

Antimetabolites, Antineoplastic ; therapeutic use ; Capecitabine ; Carcinoma, Squamous Cell ; mortality ; pathology ; therapy ; Chemoradiotherapy ; Deoxycytidine ; analogs & derivatives ; therapeutic use ; Dose Fractionation ; Esophageal Neoplasms ; mortality ; pathology ; therapy ; Esophagitis ; etiology ; Fluorouracil ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasm Recurrence, Local ; Radiation Pneumonitis ; etiology ; Radiotherapy, Conformal ; adverse effects ; methods ; Remission Induction ; Survival Rate

OBJECTIVETo evaluate retrospectively the efficacy and toxicity of capecitabine-based chemotherapy in the treatment of advanced breast cancer.

METHODSThree hundred and seventy-six patients with advanced breast cancer were treated with capecitabine-based chemotherapy regimens in our department from Sep 2002 to Sep 2009. They were divided into 3 groups. The group 1 was treated with capecitabine 1000 mg/m(2) orally twice daily on d1-d14, repeated every 3 weeks. The group 2 was treated with capecitabine as group 1, and combined with docetaxel 60 - 75 mg/m(2) intravenous infusion on d1, repeated every 3 weeks. The group 3 was treated with capecitabine as group 1, and combined with vinorelbine 25 mg/m(2) intravenous infusion on d1 and d8, repeated every 3 weeks. The median treatment period of treatment was 3 cycles.

RESULTSAmong the 376 patients, 218 patients were evaluable for response. In the group 1 the objective response rate (ORR) was 12.8% and the clinical benefit rate (CBR) was 21.6%. The CBR but not ORR of first line therapy with capecitabine was 35.2%, significantly higher than that of more than first line therapy (17.1%, P < 0.01). The ORRs for group 2 and group 3 were 53.8% and 36.4%, respectively. In the group 2 there was no significant difference in the ORR between the first line therapy and more than first line therapy. In the group 3 the ORR of first line therapy of NX regimen was 36.4%, significantly higher than that of more than first line therapy (16.7%, P < 0.01).

CONCLUSIONSThe capecitabine-based chemotherapy is effective and tolerable, and can be used not only in first line but also more than first line therapy. The single agent maintenance chemotherapy after response to combined chemotherapy can prolonge the duration of treatment for patients with metastatic breast cancer.

Adult ; Agranulocytosis ; chemically induced ; Antimetabolites, Antineoplastic ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Breast Neoplasms ; drug therapy ; pathology ; Capecitabine ; Deoxycytidine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Diarrhea ; chemically induced ; Disease Progression ; Disease-Free Survival ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Follow-Up Studies ; Hand-Foot Syndrome ; etiology ; Humans ; Leukopenia ; chemically induced ; Maintenance Chemotherapy ; Middle Aged ; Neoplasm Staging ; Remission Induction ; Retrospective Studies ; Taxoids ; administration & dosage ; Vinblastine ; administration & dosage ; analogs & derivatives