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

OBJECTIVETo assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes.

METHODSClinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX).

RESULTSAfter 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively.

CONCLUSIONSNVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III clinical trial in larger cohort.

Anthracyclines ; therapeutic use ; Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Antineoplastic Agents, Phytogenic ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bridged-Ring Compounds ; therapeutic use ; Capecitabine ; administration & dosage ; Cisplatin ; administration & dosage ; Disease-Free Survival ; Humans ; Neutropenia ; chemically induced ; Retrospective Studies ; Taxoids ; therapeutic use ; Triple Negative Breast Neoplasms ; drug therapy ; pathology ; Vinblastine ; adverse effects ; analogs & derivatives ; therapeutic use

In this study, it is to compare the effectiveness of prevention against and treatment of doxorubicin (DOX) induced cardiotoxicity by dexrazoxane and schisandrin B (Sch B) in rats. Sprague-Dawley (SD) rats were randomly divided into the following 6 groups: normal saline group, DOX group, DOX+DEX group, DOX+Sch B (80 mg x kg(-1)) group, DOX+Sch B (40 mg x kg(-1)) group and DOX+Sch B (20 mg x kg(-1)) group. The results showed that Sch B could combat the increase of myocardial enzymes in peripheral blood, decrease of the enzyme activity of myocardial tissue antioxidant enzymes and disorders of systolic and diastolic function of heart in rats intravenously injected with doxorubicin (15 mg x kg(-1)). Sch B was better than DEX in protecting rat against DOX-induced the symptoms. Sch B could protect rat against DOX-induced acute cardiomyopathy and has clinical potential applications.
Animals ; Antibiotics, Antineoplastic ; adverse effects ; Antioxidants ; metabolism ; Cardiomyopathies ; chemically induced ; drug therapy ; Cardiotoxicity ; drug therapy ; Cyclooctanes ; therapeutic use ; Dexrazoxane ; therapeutic use ; Doxorubicin ; adverse effects ; Heart ; physiopathology ; Lignans ; therapeutic use ; Myocardium ; enzymology ; Polycyclic Compounds ; therapeutic use ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo investigate the toxicity attenuation and efficacy potentiation effects of Sijunzi decoction (SJZD) on bladder carcinoma treated by chemotherapy in mice.

METHODST739 mice were randomly divided into 8 groups after subcutaneous inoculation of bladder carcinoma cells, the control group (A); two mitomycin C (MMC) group, treated with MMC of routine dosage (B) and low-dosage (C) respectively; three SJZD groups, treated with SJZD of high (D), medium (E) and low-dosage (F) respectively; and two combined treatment groups, treated with SJZD of high-dosage + MMC of routine dosage(G) and SJZD of high-dosage + MMC of low-dosage(H). The medication was begun at 24 hrs after inoculation. The tumor inhibitory rate, activity of peritoneal macrophages after 14 days of treatment and change of peripheral white blood cells after 7 days of treatment were determined and the survival time of mice was observed.

RESULTSThe survival time of mice in Group D was significantly higher than that in Group A (P < 0.05), while those in Group E and F showed insignificant difference as compared with those in Group A (P > 0.05). The highest tumor inhibitory rate was shown in Group B, but the survival time in that group showed no significant difference as compared to those in Group A (P > 0.05). The longest survival time (32.7 +/- 1.3 days) was shown in Group H, which was obviously different to that in other groups (P < 0.05). And the leukocyte counts and macrophage activity in Group H were better than those in Group B, C and G (P < 0.05), except that the tumor inhibitory rate was significantly lower than that in Group B, C and G (P < 0.05).

CONCLUSIONCombined chemotherapy of SJZD with low dosage MMC has definite effect in inhibiting tumor growth in mice with bladder carcinoma, displaying special effects of toxicity attenuation and efficacy potentiation.

Animals ; Antibiotics, Antineoplastic ; adverse effects ; Antineoplastic Agents, Phytogenic ; therapeutic use ; Carcinoma, Transitional Cell ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Leukocyte Count ; Male ; Mice ; Mice, Inbred Strains ; Mitomycin ; adverse effects ; Phytotherapy ; Random Allocation ; Urinary Bladder Neoplasms ; drug therapy

OBJECTIVETo evaluate the cardioprotective effects of dexrazoxane (DEX) on breast cancer patients who received anthracycline-containing chemotherapy.

METHODSA total of 122 breast cancer patients after operation were randomly divided into two groups: The experimental group of 61 cases treated with EPI plus DEX (DEX:EPI = 10:1) as adjuvant chemotherapy regimen, and the control group of 61 cases treated with EPI but without DEX. All patients received four cycles of adjuvant chemotherapy and their changes of specific cardiac functional status and hematology status before and after chemotherapy, as well as non-cardiac toxicity were observed and analyzed.

RESULTSBrain natriuretic peptide (BNP) before chemotherapy and after four cycles of chemotherapy in the control group was (106.78 ± 4.52)×10(-6) µg/ml and (187.19 ± 8.71)×10(-6) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (102.34 ± 8.76)×10(-6) µg/ml and (105.29 ± 7.21)×10(-6) µg/ml, respectively, without a significant difference (P > 0.05). Cardiac troponin T (cTnT) before chemotherapy and after four cycles of chemotherapy in the control group was (12.55 ± 2.73)×10(-3) µg/ml and ( 31.05 ± 7.10 )×10(-3) µg/ml, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (12.70 ± 2.15)×10(-3) µg/ml and (13.65 ± 7.82)×10(-3) µg/ml, respectively, without a significant difference (P > 0.05). The hart rate (HR) before chemotherapy and after four cycles of chemotherapy in the control group, was 75.32 ± 7.14 bpm and 89.60 ± 9.21 bpm, respectively, with a significant difference (P < 0.05). It in the experimental group was 78.60 ± 6.29 bpm and 83.10 ± 7.56 bpm, respectively, without a significant difference (P > 0.05). The left ventricular ejection fraction (LVEF) before chemotherapy and after four cycles of chemotherapy in the control group was (65.23 ± 7.82)% and (55.21 ± 7.23)%, respectively, with a significant difference between them (P < 0.05). It in the experimental group was (64.12 ± 6.25)% and (59.6 ± 4.72)%, respectively, without a significant difference (P > 0.05). The absolute neutrophil count before chemotherapy and after four cycles of chemotherapy in the control group was (3.95 ± 1.36)×10(9)/L and (3.50 ± 1.52)×10(9)/L, respectively, without a significant difference (P > 0.05). It in the experimental group, was (4.96 ± 1.41)×10(9)/L and (3.10 ± 1.26)×10(9)/L, respectively, with a significant difference (P < 0.05). The incidence of grade I-IV bone marrow suppression in the experimental group was 21.3%, 16.4%, 24.6%, and 4.9%, respectively. It in the control group was 16.4%, 11.5%, 9.8%, and 5.5%, respectively, with a significant difference (P < 0.05).

CONCLUSIONSCardiac toxicity after anthracycline treatment in breast cancer patients may be significantly reduced by DEX, without increase of non-cardiac and and non-hematologic toxicity. DEX combined with anthracycline increases the risk of bone marrow suppression, therefore, peripheral blood picture should be monitored or routine bone marrow support may be needed.

Adolescent ; Adult ; Aged ; Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Bone Marrow ; drug effects ; Breast Neoplasms ; drug therapy ; metabolism ; pathology ; physiopathology ; surgery ; Cardiovascular Agents ; adverse effects ; therapeutic use ; Chemotherapy, Adjuvant ; Epirubicin ; adverse effects ; therapeutic use ; Female ; Follow-Up Studies ; Heart Rate ; drug effects ; Humans ; Leukocyte Count ; Middle Aged ; Natriuretic Peptide, Brain ; metabolism ; Neutrophils ; cytology ; Razoxane ; adverse effects ; therapeutic use ; Stroke Volume ; drug effects ; Young Adult

Objective: To analyze the value of 3-dimensional speckle tracking echocardiograghy (3D-STE) derived strain parameters on the detection of subclinical myocardial deformation alterations in patients with lymphoma treated with anthracycline agents. Methods: This study was a retrospective study. A total of 37 patients with newly diagnosed diffuse large B cell non-Hodgkin lymphoma between December 2012 and December 2014 in Cancer Center, Fudan university were included. 3D-STE strain measurements were performed at baseline (T0),after the completion of two therapy circles (T1) and at the end of anthracycline regimen chemotherapy (Te). Echocardiography images were analyzed on the TTA workstation, and the indexes included left atrial minimum volume (LAVmin), left atrial emptying index (LAEF), left atrial active emptying index (LAAEF), as well as the left ventricular global longitudinal strain (LVGLS), left ventricular global circumferential strain (LVGCS), left atrial global longitudinal strain (LAGLS). The overall left atrioventricular longitudinal strain (LAVGLS) was calculated, which was the sum of the absolute values of LVGLS and LAGLS. The changes of left ventricular strain indexes measured by 3D-STE at different time points of patients were evaluated. Results: Thirty-seven patients with DLBCL, aged (48.3±12.1)years, including 23 males (63.9%), were enrolled. Compared with baseline, LVGLS (T1: (-18.63±4.73)% vs. (-22.13±4.40)%, P=0.001; Te:(-18.26±4.64)% vs. (-22.13±4.40)%, P<0.001), LAGLS (T1: (20.41±5.56)% vs. (23.98±5.59)%, P=0.003; Te: (17.60±3.96)% vs. (23.98±5.59)%, P<0.001) and LAVGLS (T1: (39.05±7.60)% vs. (46.11±7.77)%, P<0.001; Te: (40.34±8.55)% vs. (46.11±7.77)%, P<0.001) were all deteriorated at the T1 and Te. While LVGCS ((-21.98±5.82)% vs. (-26.15±7.51)%, P=0.010), LAVmin ((23.93±7.29)ml vs. (20.33±7.03)ml, P=0.029), LAEF ((28.94±11.16)% vs. (35.79±11.12)%, P=0.002) and LAAEF ((11.93±10.00)% vs. (18.10±9.96)%, P=0.013) were decreased only until Te. Conclusions: 3D-STE strain measurements could detect early myocaridial function alteration in patients receiving anthracycline regimen chemotherapy, thus may provide a novel approach to monitor anthracycline caused myocardial toxicity.
Male ; Humans ; Anthracyclines/therapeutic use* ; Ventricular Function, Left ; Retrospective Studies ; Heart Ventricles ; Antibiotics, Antineoplastic/adverse effects* ; Polyketides/pharmacology* ; Lymphoma/drug therapy*

OBJECTIVETo evaluate the value of cardiac troponin I (CTnI) measurement in predicting anthracycline-induced cardiotoxicity in patients with breast cancer.

METHODSThis study was conducted among 186 breast cancer patients receiving anthracycline-based chemotherapy. Serum cTnI concentrations before and after each cycle of the chemotherapy and the left ventricular ejection fraction (LVEF) before and at the 2nd, 4th and 6th months of the treatment were recorded. According to serum cTnI concentration, the patients were divided into CTnI+ group (with serum CTnI concentration of no less than 0.1 ng/ml, n=60) and CTnI- (<0.1 ng/ml) group (n=126).

RESULTSNo patients in this series experienced cardiac heart failure (CHF). The number of patients with a LVEF reduction by over 10% from the baseline was 16 (26.7%) in CTnI+ group, as compared to 7 (5.6%) in CTnI- group, showing a significant difference between the two groups (P<0.01).

CONCLUSIONCTnI can be a useful marker for early prediction of anthracycline-induced cardiotoxicity in patients with breast cancer.

Adult ; Aged ; Anthracyclines ; adverse effects ; therapeutic use ; Antibiotics, Antineoplastic ; therapeutic use ; Biomarkers ; blood ; Breast Neoplasms ; drug therapy ; Cardiotoxins ; adverse effects ; Female ; Humans ; Middle Aged ; Myocardium ; metabolism ; Troponin I ; blood ; Young Adult

OBJECTIVETo evaluate the efficacy and safety of IDA (Haizheng Parmacy, China) in the treatment of acute leukemia.

METHODSA multi-institutional single-blind randomized controlled clinical trial was carried out. A total of 155 newly diagnosed patients with AML and ALL were enrolled. The patients were randomly divided into two groups, one was given IDA (n = 77) and the other given zevodas (Pharnacia & Upjohn, n = 78) for comparison.

RESULTSAll the patients enrolled in this trial were eligible for assessment of side effects, and 129 patients for evaluation of overall response rate. In patients treated with IDA vs zevodas, the overall response rate (OR) was 78.1% vs 76.9%, CR was 68.8% vs 67.7%; in AML patients, OR was 82.4% vs 71.8%, and CR was 76.5% vs 64.1%; in ALL patients, OR was 80.0% vs 81.8%, and CR was 68.0% vs 68.2%. There was no sitatistically significant difference in hematologic and non-hematologic toxicities between the two groups.

CONCLUSIONThe efficacy of IDA in the treatment of acute leukemia is comparable to that of zevodas. Both have similar toxic side effects.

Adolescent ; Adult ; Aged ; Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; China ; Female ; Humans ; Idarubicin ; adverse effects ; therapeutic use ; Leukemia, Myeloid, Acute ; drug therapy ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; Single-Blind Method

In order to assess the effect of long-term versus short-term intravesical chemotherapy in preventing the recurrence of patients with non-muscle-invasive bladder cancer, we searched several databases with words as mesh terms and free text words to find all eligible randomized clinical trials (RCTs) for the comparison of the two strategies of instillation durations. "Observed-Expected events research (O-E)" and "Variance (V)" for calculating hazard ratio (HR) were used in Revman 5.2 software recommended by Cochrane Collabration for data analysis. Sensitivity and subgroup analysis were selected to minish heterogeneity. GRADEpro 3.6 profile recommended by Cochrane Collabration was employed for quality assessment of analyses. Finally, 13 eligible RCTs with 4216 patients were included in this review and 16 comparisons from 13 trials were involved for analysis. The pooled analysis revealed no significant difference between long-term and short-term duration [HR=0.99, 95% CI (0.89, 1.11), P=0.89]. Within the subgroup analysis, patients benefited from long-term instillations with a start regimen of one immediate instillation [HR=0.83, 95% CI (0.69, 1.00), P=0.05]. But patients were not suitable to receive long-term instillations with epirubicin (EPI) [HR=1.01, 95% CI (0.91, 1.13), P=0.78]. The progression rate was not reduced after long-term instillations [HR=0.96, 95% CI (0.66, 1.39), P=0.82]. From our results, patients should not receive introvesical chemotherapy more than half a year. In contrast, patients with one immediate instillation are preferred to have a long-term duration at least one year. Long-term instillations can not reduce the progression rate.
Administration, Intravesical ; Antibiotics, Antineoplastic ; administration & dosage ; adverse effects ; therapeutic use ; Drug Therapy ; methods ; trends ; Epirubicin ; administration & dosage ; adverse effects ; therapeutic use ; Neoplasm Recurrence, Local ; Randomized Controlled Trials as Topic ; Time Factors ; Treatment Outcome ; Urinary Bladder Neoplasms ; drug therapy

OBJECTIVETo study relationship between daunorubicin (DNR) pharmacokinetics and efficacy and toxicity in children with acute leukemia.

METHODS(1) The concentration of DNR in plasma of children with acute leukemia was determined by high performance liquid chromatography (HPLC)-fluorescence detection method. Plasma was sampled frequently from the start of the infusion till the end of 24 h. DNR pharmacokinetics was studied by determination of the concentrations. (2) Efficacy and toxicity were monitored in each period after chemotherapy. Laboratory studies included examination of bone marrow, white blood cell count, electrocardiogram, echocardiogram, myocardial enzymogram, the liver and kidney function.

RESULTS(1) DNR was eliminated from plasma in a two-compartment manner. The maximum concentration was seen 1 - 3 h after infusion. Cmax was 63.50 microg/L. Tmax was 1.45 h. The concentration decreased quickly to a low level of about 11.52 microg/L from the end of 2 hours infusion. There was a large inter-individual difference in pharmacokinetic parameters of DNR. The difference of CL was 9-fold, AUC was 8-fold, Cmax was 5-fold. (2) CL of male patients [57.99 L/(h.m(2))] was significantly lower than that of female patients [93.71 L/(h.m(2))] (P < 0.05). Tmax of children older than 6 years was 1.1 h, and that of children younger than 6 years was 1.8 h (P < 0.05); Cmax of children older than 6 years was 90.77 microg/L, younger than 6 years was 57.44 microg/L (P < 0.05).

CONCLUSION(1) There is a large inter-individual difference in pharmacokinetic parameters of DNR in children. It may predict individual variety of efficacy and toxicity. Therapeutic drug monitoring is important. (2) Male patients and children older than 6 years had a higher bioavailability and lower metabolism, toxicity may easily occur in such children, therefore they may need lower dose.

Antibiotics, Antineoplastic ; adverse effects ; pharmacokinetics ; therapeutic use ; Child ; Child, Preschool ; Chromatography, High Pressure Liquid ; Daunorubicin ; adverse effects ; pharmacokinetics ; therapeutic use ; Drug Monitoring ; Female ; Humans ; Infant ; Leukemia ; drug therapy ; metabolism ; Male