As a new type of anthracyclines, pegylated liposomal doxorubicin (PLD) is widely used in the treatment of a variety of malignant tumors, including soft tissue sarcoma, ovarian cancer, breast cancer, multiple myeloma, and so on. Compared with traditional anthracyclines, PLD can significantly decrease the incidences of adverse events such as cardiac toxicity and alopecia. However, the use of PLD will be accompanied with toxic side effects such as hand-foot syndrome, oral mucositis, and infusion reaction. This consensus will mainly focus on the mechanism, prevention and treatment of adverse events of PLD, in order to improve the therapeutic efficacy of PLD and life quality of patients.
Antibiotics, Antineoplastic ; adverse effects ; therapeutic use ; Consensus ; Doxorubicin ; adverse effects ; analogs & derivatives ; therapeutic use ; Drug-Related Side Effects and Adverse Reactions ; prevention & control ; Female ; Hand-Foot Syndrome ; complications ; Humans ; Neoplasms ; drug therapy ; Polyethylene Glycols ; adverse effects ; therapeutic use ; Practice Guidelines as Topic ; Stomatitis ; complications

OBJECTIVETo explore the safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing chemotherapy-induced neutropenia in patients with breast cancer and non-small cell lung cancer (NSCLC), and to provide the basis for clinical application.

METHODSAccording to the principle of open-label, randomized, parallel-group controlled clinical trial, all patients were randomized by 1∶1∶1 into three groups to receive PEG-rhG-CSF 100 μg/kg, PEG-rhG-CSF 6 mg, or rhG-CSF 5 μg/kg, respectively. The patients with breast cancer received two chemotherapy cycles, and the NSCLC patients received 1-2 cycles of chemotherapy according to their condition. All patients were treated with the combination chemotherapy of TAC (docetaxel+ epirubicin+ cyclophosphamide) or TA (docetaxel+ epirubicin), or the chemotherapy of docetaxel combined with carboplatin, with a 21 day cycle.

RESULTSThe duration of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg and PEG-rhG-CSF 6 mg groups were similar with that in the rhG-CSF 5 μg/kg group (P>0.05 for all). The incidence rate of grade 3-4 neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group, and G-CSF 5 μg/kg group were 69.7%, 68.4%, and 69.5%, respectively, with a non-significant difference among the three groups (P=0.963). The incidence rate of febrile neutropenia in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg/kg group were 6.1%, 6.4%, and 5.5%, respectively, showing no significant difference among them (P=0.935). The incidence rate of adverse events in the PEG-rhG-CSF 100 μg/kg group, PEG-rhG-CSF 6 mg group and G-CSF 5 μg / kg group were 6.7%, 4.1%, and 5.5%, respectively, showing a non-significant difference among them (P=0.581).

CONCLUSIONSIn patients with breast cancer and non-small cell lung cancer (NSCLC) undergoing TAC/TA chemotherapy, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF at 48 hours after chemotherapy show definite therapeutic effect with a low incidence of adverse events and mild adverse reactions. Compared with the continuous daily injection of rhG-CSF 5 μg/kg/d, a single 100 μg/kg injection or a single fixed 6 mg dose of PEG-rhG-CSF has similar effect and is more advantageous in preventing chemotherapy-induced neutropenia.

Antineoplastic Agents ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; Breast Neoplasms ; drug therapy ; Carboplatin ; administration & dosage ; adverse effects ; Carcinoma, Non-Small-Cell Lung ; drug therapy ; Cyclophosphamide ; administration & dosage ; adverse effects ; Epirubicin ; administration & dosage ; adverse effects ; Female ; Granulocyte Colony-Stimulating Factor ; therapeutic use ; Humans ; Incidence ; Induction Chemotherapy ; Lung Neoplasms ; drug therapy ; Neutropenia ; chemically induced ; epidemiology ; prevention & control ; Polyethylene Glycols ; Recombinant Proteins ; administration & dosage ; Taxoids ; administration & dosage ; adverse effects

Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma. Combination therapy of pegylated interferon-alpha (PEG-IFN-α) and ribavirin (RBV) is a current standard treatment for chronic HCV infection in Korea, which has considerable adverse effects. Acute pancreatitis is a rare complication of PEG-IFN-α administration. We report a case of a 62-year-old female who experienced acute pancreatitis after 4 weeks of PEG-IFN-α-2a and RBV combination therapy for chronic HCV infection. The main cause of the acute pancreatitis in this case was probably PEG-IFN-α rather than RBV for several reasons. A few cases have been reported in which acute pancreatitis occurred during treatment with PEG-IFN-α-2b. This is the first report of acute pancreatitis associated with PEG-IFN-α-2a in Korea.
Amylases/analysis ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnostic imaging/*drug therapy ; Humans ; Interferon-alpha/adverse effects/*therapeutic use ; Lipase/analysis ; Middle Aged ; Pancreatitis/*etiology ; Polyethylene Glycols/adverse effects/*therapeutic use ; Recombinant Proteins/adverse effects/therapeutic use ; Republic of Korea ; Ribavirin/therapeutic use ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Chronic hepatitis C (CHC) is a major comorbidity in patients with hemophilia. However, there are no published data on the efficacy of antiviral therapy in Korea. We assessed the safety and efficacy of combination therapy with peginterferon alpha-2a plus ribavirin for CHC in hemophilia. METHODS: Patients (n=115) were enrolled between March 2007 and December 2008. Seventy-seven patients were genotype 1 or 6, and 38 patients were genotype 2 or 3. We evaluated rapid virologic responses (RVRs), early virologic response (EVRs), end-of-treatment response (ETRs), sustained virologic response (SVRs), and relapses. Safety evaluations included adverse events and laboratory tests. RESULTS: Eleven patients were excluded from the study because they had been treated previously. Among the remaining 104 treatment-naive patients, RVR was achieved in 64 (60.6%), ETR was achieved in 95 (91.3%), and SVR was achieved in 89 (85.6%). Relapse occurred in eight patients (8.9%). Common adverse events were hair loss (56.7%) and headache (51.0%). Common hematologic adverse events were neutropenia (22.1%), anemia (27.9%), and thrombocytopenia (3.8%). However, there were no serious adverse events such as bleeding. RVR was the only predictor of SVR in multivariate analysis. CONCLUSIONS: Peginterferon alpha-2a plus ribavirin combination treatment produced a favorable response rate in CHC patients with hemophilia without serious adverse events.
Adult ; Aged ; Antiviral Agents/adverse effects/*therapeutic use ; Drug Therapy, Combination ; Fatigue/etiology ; Female ; Genotype ; Headache/etiology ; Hemophilia A/*complications ; Hepacivirus/genetics ; Hepatitis C, Chronic/complications/*drug therapy/virology ; Humans ; Interferon-alpha/adverse effects/*therapeutic use ; Liver/pathology ; Male ; Middle Aged ; Neutropenia/etiology ; Polyethylene Glycols/adverse effects/*therapeutic use ; RNA, Viral/blood ; Recombinant Proteins/adverse effects/therapeutic use ; Recurrence ; Republic of Korea ; Ribavirin/adverse effects/*therapeutic use ; Treatment Outcome

BACKGROUND/AIMS: Performance of polyethylene glycol solution (PEG) is often unsatisfactory as bowel preparation agent for colonoscopy. In order to provide equivalent efficacy with better patient tolerance, sodium phosphate tablet (SPT) has been developed. This study was carried out to compare the efficacy and compliance of two bowel preparation methods: PEG with ascorbic acid (PEGA) vs. SPT preparation. METHODS: A multicenter, randomized controlled trial was performed. Primary efficacy variable was overall quality of colon cleansing assessed by Boston bowel preparation scale (BBPS) during colonoscopy. Patient's satisfaction and adverse events were evaluated by means of symptom questionnaire completed by each patient immediately before colonoscopy. RESULTS: A total of 189 patients were randomly assigned to undergo pre-colonoscopic bowel preparation with either SPT (n=96) or PEGA (n=93). Overall BBPS score was 8.3+/-1.12 in the SPT group and 8.4+/-0.96 in the PEGA group (p=0.441). Among the 189 patients, 90 had polyps (47.6%) and 50 had adenomas (26.5%). The polyp/adenoma detection rate was 54.2% (n=52)/27.1% (n=26) for SPT group and 40.9% (n=38)/25.8% (n=24) for PEGA group (p=0.079 and 0.790, respectively). More number of patients were unable to take the prescribed dose of PEGA compared with the SPT regimen (8.6% vs. 2.0%, p=0.045). Overall satisfaction score was 7.9+/-1.63 in the SPT group and 7.4+/-1.53 in the PEGA group (p=0.022). CONCLUSIONS: Degree of colon preparation, polyp/adenoma detection rate and adverse effect were similar between SPT group and PEGA group. Patient compliance and satisfaction were greater in the SPT group.
Abdominal Pain/etiology ; Adenoma/pathology ; Adult ; Ascorbic Acid/*therapeutic use ; Cathartics/adverse effects/*therapeutic use ; Colonic Polyps/pathology ; *Colonoscopy ; Female ; Humans ; Male ; Middle Aged ; Nausea/etiology ; Patient Satisfaction ; Phosphates/*therapeutic use ; Polyethylene Glycols/*therapeutic use ; Surveys and Questionnaires

BACKGROUND/AIMS: Inpatient status can cause inadequate bowel preparation. The majority of previous studies regarding bowel preparation have focused on comparing the effects of different purgative regimens in outpatients. However, data on bowel preparation for inpatients are lacking. The aim of this study was to investigate whether bisacodyl plus polyethylene glycol (PEG) can improve bowel preparation in hospitalized patients. METHODS: A prospective, randomized and observer-blind study was performed. A total of 196 hospitalized patients undergoing colonoscopy were randomized to receive 4 L PEG (PEG only group) or 4 L PEG+bisacodyl 10 mg (bisacodyl added group). The adequacy of bowel preparation was scored using the Ottawa bowel preparation scale. RESULTS: One hundred and eighty-three subjects completed the study; 96 in the bisacodyl added group and 87 in the PEG only group. There were no significant differences between the bisacodyl added group and the PEG only group with respect to the score of bowel cleansing (3.59+/-2.81 vs. 3.82+/-3.03, p=0.607), quality of bowel cleansing (adequate preparation 89.6% vs. 85.1%, p=0.380), and overall adverse events (66.7% vs. 52.9%, p=0.057). However, a larger proportion of patients in the PEG only group were able to ingest the entire solution as prescribed than in the bisacodyl added group (98.9% vs. 75.0%, p<0.001). CONCLUSIONS: In hospitalized patients, the quality of bowel preparation did not differ depending on whether bisacodyl is added or not. In addition, patient compliance based on consumption of cleansing agent was better in the PEG only group.
Adult ; Aged ; Bisacodyl/adverse effects/*therapeutic use ; Cathartics/adverse effects/*therapeutic use ; Colon/pathology ; *Colonoscopy ; Female ; Humans ; Male ; Middle Aged ; Nausea/etiology ; Polyethylene Glycols/adverse effects/*therapeutic use ; Prospective Studies

OBJECTIVETo analyze the clinical characteristics and the course of diagnosis and therapy of PEG-asparaginase associated pancreatitis (AAP) in childhood, and to reveal the pathophysiology of AAP, enhance the ability of diagnosis and treament.

METHODData of 13 cases with AAP in childhood seen from March 2011 to March 2014 were analyzed with regard to clinical manifestations, laboratory findings, imaging feature and treatment.

RESULTAAP was found in 12 of acute lymphoblastic leukemia (ALL) and 1 of non-Hodgkin's lymphoma (NHL), 8 were boys and 5 were girls, with a mean age 6 years. In 12 cases AAP occurred during the induction-remission treatment, in 1 case during the maintenance- intensification phase. AAP occurred after a median of two doses, and 9 d (median) from the latest administration of PEG-asparaginase. The major manifestations of AAP was abdominal pain (11/13) . At the time of AAP diagnosis during the first 48 hours the median peak serum amylase and serum lipase levels were 559 U/L (range 118-1 585, upper normal limit: 125) and 934 U/L (range 221-1 673, upper normal limit: 300). Three cases with serum amylase and serum lipase levels above 3 times upper normal limit were repeatedly complicated with pancreatic pseudocyst; 11 patients had abnormal CT imaging, 8 cases revealed effusion around the pancreas, and 4 cases had pseudocyst. Therapy with ulinastatin, octreotide acetate, glucocorticoid could relieve abdominal pain significantly. Three cases underwent abdominal puncture drainage and 5 cases fulfilled nasojejunal nutrition therapy. Nine of them were cured, 4 developed pseudocyst, in 2 AAP vanished gradually and 2 died with pseudocyst.

CONCLUSIONThe major manifestations of AAP were abdominal pain, but sometimes apparent and sometimes latent. Condition of acute pancreatitis may exacerbate rapidly and easily. Early identification had significance. Pancreatic pseudocyst suggested a poor prognosis.

Acute Disease ; Asparaginase ; adverse effects ; therapeutic use ; Child ; Female ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; Male ; Pancreatic Pseudocyst ; Pancreatitis ; chemically induced ; diagnosis ; therapy ; Polyethylene Glycols ; adverse effects ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

OBJECTIVETo observe the efficacy of polyethylene glycol conjugated asparaginase (peg-asp) for induction treatment of children with newly diagnosed acute lymphoblastic leukemia (ALL).

METHODA total of 268 newly diagnosed children with ALL enrolled in CCLG-2008 from January, 2010 to August, 2012 were analyzed. Patients received either native Escherichia coli asparaginase or pegaspargase along with multiagent chemotherapy during remission induction treatment. Status of bone marrow aspiration was assessed on day 15, day 33 (M1, M2, M3).

RESULTOf the 268 patients stratified, 37.3% (n = 100) were SR, 32.1% (n = 86) were IR, and 31.6% (n = 82) were HR; 159 patients received native Escherichia coli asparaginase and 109 patients received pegaspargase. Characteristics of two groups in age, sex, blood count at diagnosis, immunophenotype and response to prednisolone had no significant difference (P > 0.05). Bone marrow status on day 15 in pegaspargase group was M1 in 70 (64.2%) cases, M2 in 23 (21.1%) and M3 in 16 (14.7%), while in native Escherichia coli asparaginase group, M1 in 112 (70.4%) cases, M2 in 21 (13.2%) and M3 in 26 (16.4%), respectively (χ(2) = 2.938, P = 0.230). Bone marrow status on day 33 was M1 in 105 (96.3%), M2 in 3 (2.8%) and M3 in 1 (0.9%) in pegaspargase group, while it was M1 in 154 (96.9%) cases, M2 in 5 (3.1%) and M3 in native Escherichia coli asparaginase group, respectively (χ(2) = 1.494, P = 0.474).

CONCLUSIONDomestic pegaspargase of our country can achieve the similar efficacy in induction treatment for ALL patients as compared with native Escherichia coli asparaginase. The drug could be considered as not only the choice for allergic patients but also a first-line alternative for new patients.

Adolescent ; Antineoplastic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Asparaginase ; administration & dosage ; adverse effects ; Bone Marrow Cells ; drug effects ; pathology ; Case-Control Studies ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Polyethylene Glycols ; administration & dosage ; adverse effects ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; pathology ; Prednisone ; administration & dosage ; adverse effects ; Remission Induction ; Retrospective Studies ; Treatment Outcome

The chemotherapy agent L-asparaginase (L-asp) has been an important part of acute lymphoblastic leukemia therapy for over 30 years. It is evident that L-asp has a long-term curative effect. However, L-asp is associated with high incidence of adverse reactions. This has prompted the development of pegylated asparaginase (PEG-asp), which has undergone extensive testing. Apparently, PEG-asp has a prolonged half-life with a better tolerance profile while retaining the antileukemic effect. In this review, we attempt to outline the history of clinical application of L-asp, the pharmacological and clinical potential of various preparations of L-asp, the development of PEG-asp, and the clinical application and adverse events of PEG-asp. The literatures reviewed in this article is collected through online search of the major databases both in English and Chinese.
Antineoplastic Agents ; therapeutic use ; Asparaginase ; adverse effects ; pharmacokinetics ; pharmacology ; therapeutic use ; Blood Coagulation Disorders ; chemically induced ; Humans ; Pancreatitis ; chemically induced ; Polyethylene Glycols ; adverse effects ; pharmacokinetics ; pharmacology ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-alpha and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-alpha and ribavirin.
Antifungal Agents/therapeutic use ; Antiviral Agents/*adverse effects ; Cryptococcus neoformans/immunology/*pathogenicity ; Drug Therapy, Combination ; Female ; Hepatitis C, Chronic/diagnosis/*drug therapy/immunology ; Humans ; Immunocompromised Host ; Interferon-alpha/*adverse effects ; Meningitis, Cryptococcal/drug therapy/immunology/*microbiology ; Middle Aged ; Opportunistic Infections/diagnosis/drug therapy/immunology/*microbiology ; Polyethylene Glycols/*adverse effects ; Recombinant Proteins/adverse effects ; Ribavirin/*adverse effects ; Time Factors ; Treatment Outcome