Although olaparib has demonstrated substantial clinical benefits as maintenance therapy in BRCA mutation-carrying women with newly diagnosed advanced ovarian cancer, its effectiveness in patients without BRCA mutations remains poorly investigated. This study aims to provide the first evidence on the efficacy of mono-olaparib maintenance therapy in such context. Using real-world data from 11 high-volume tertiary care centers in China, a retrospective cohort study was conducted to assess the efficacy and safety of olaparib as first-line maintenance therapy in patients with BRCA wild-type ovarian cancer. The primary objective was 1-year progression-free survival rate. Safety was also evaluated. Fifty patients with a median age of 54 years were included, and all of them tested negative for BRCA mutations but positive for homologous recombination deficiency (HRD). The 1-year PFS rate was 75.2% (95% CI, 63.4 to 89.2), and the median PFS was 21.0 months (95% CI, 13.8 to 28.2). All the patients received olaparib at a starting dose of 300 mg twice daily, and none experienced serious adverse events (AEs). Eight (16%) patients had dose adjustment, but none discontinued olaparib treatment due to AEs. We provide the first evidence that mono-olaparib could be a safe and effective maintenance treatment option for patients newly diagnosed with HRD-positive/BRCA wild-type ovarian cancer.
Humans ; Female ; Phthalazines/adverse effects* ; Piperazines/administration & dosage* ; Middle Aged ; Ovarian Neoplasms/genetics* ; Retrospective Studies ; Adult ; Aged ; Poly(ADP-ribose) Polymerase Inhibitors/administration & dosage* ; China ; Maintenance Chemotherapy ; BRCA2 Protein/genetics* ; Antineoplastic Agents/adverse effects* ; Progression-Free Survival ; BRCA1 Protein/genetics*

PURPOSE: Urapidil is putatively effective for patients with hypertension and acute heart failure, although randomized controlled trials thereon are lacking. We investigated the efficacy and safety of intravenous urapidil relative to that of nitroglycerin in older patients with hypertension and heart failure in a randomized controlled trial. MATERIALS AND METHODS: Patients (>60 y) with hypertension and heart failure were randomly assigned to receive intravenous urapidil (n=89) or nitroglycerin (n=91) for 7 days. Hemodynamic parameters, cardiac function, and safety outcomes were compared. RESULTS: Patients in the urapidil group had significantly lower mean systolic blood pressure (110.1±6.5 mm Hg) than those given nitroglycerin (126.4±8.1 mm Hg, p=0.022), without changes in heart rate. Urapidil was associated with improved cardiac function as reflected by lower N terminal-pro B type natriuretic peptide after 7 days (3311.4±546.1 ng/mL vs. 4879.1±325.7 ng/mL, p=0.027) and improved left ventricular ejection fraction (62.2±3.4% vs. 51.0±2.4%, p=0.032). Patients given urapidil had fewer associated adverse events, specifically headache (p=0.025) and tachycardia (p=0.004). The one-month rehospitalization and all-cause mortality rates were similar. CONCLUSION: Intravenous administration of urapidil, compared with nitroglycerin, was associated with better control of blood pressure and preserved cardiac function, as well as fewer adverse events, for elderly patients with hypertension and acute heart failure.
Acute Disease ; Aged ; Antihypertensive Agents/*administration & dosage ; Blood Pressure/drug effects ; Cause of Death ; Female ; Heart Failure/*drug therapy/physiopathology ; Heart Rate/drug effects/physiology ; Hemodynamics ; Humans ; Hypertension/*drug therapy/physiopathology ; Injections, Intravenous ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Nitroglycerin/administration & dosage ; Peptide Fragments/blood ; Piperazines/*administration & dosage ; Ventricular Function, Left/drug effects/physiology

OBJECTIVETo investigate the factors which may influence the imatinib plasma concentration in Chinese patients with gastrointestinal stromal tumor(GIST), and to illuminate the significance of monitoring imatinib plasma concentration in adjuvant therapy for patients with GIST.

METHODSA cross-sectional study with 60 GIST patients who accepted the imatinib therapy after surgery was conducted. They were respectively administrated in 10 domestic hospitals from December 2014 to April 2016, including The First Affiliated Hospital of Nanjing Medical University(n=28), The Affiliated Hospital of Nantong University(n=9), The Affiliated Hospital of Xuzhou Medical College(n=6), Nanjing Drum Tower Hospital(n=5), The Second Affiliated Hospital of Nanjing Medical University (n=2), Jingling Hospital (n=2), The Second People's Hospital of Lianyungang(n=2), Shandong Provincial Hospital(n=2), Jiangsu Province Tumor Hospital(n=2), and The First Affiliated Hospital of Zhejiang University(n=2). Some specific time points for collecting blood sample before and after taking imatinib were determined, then liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used for monitoring imatinib plasma concentration in patients with GIST. Linear regression analysis was used for the correlation analysis of imatinib plasma concentration with dosage, clinicopathologic feature and side effect.

RESULTSPatients who could not tolerate 400 mg imatinib per day(n=3) received 300 mg per day. There was no significant difference in imatinib plasma concentration between patients with 300 mg and those with 400 mg imatinib(n=53)(P=0.527). However, the imatinib plasma concentration in patients with 600 mg imatinib per day (n=4) was significantly higher as compared to those with 400 mg(P=0.000). Linear regression analysis indicated a negative correlation between the imatinib plasma concentration in patients with 400mg imatinib per day for 90 days continuously and body surface area(R=0.074, P=0.035), but no significant correlations of with age, creatinine clearance and serum albumin concentration were observed (all P>0.05). The differences in imatinib plasma concentration were not statistically significant between patients of different gender and those taking proton-pump inhibitor (PPI) or not (both P>0.05). Difference in imatinib plasma concentration between patients with different surgery was significant (P=0.026). Compared to patients who underwent wedge resection, enterectomy and other surgeries, the imatinib plasma concentration of patients with subtotal gastrectomy or total gastrectomy decreased significantly (all P<0.05). After 90 days of taking imatinib continuously, linear regression analysis revealed a negative correlation between imatinib plasma concentration in patients with 400 mg imatinib per day and white blood cell count (R=0.103, P=0.013), and a positive correlation with serum alanine aminotransferase (ALT) concentration (R=0.076, P=0.033).

CONCLUSIONSThe imatinib plasma concentration in patients with larger body surface area, subtotal gastrectomy or total gastrectomy may be lower. For these patients, dosage of imatinib should be considered to increase in order to achieve effective plasma concentration. Excessive imatinib plasma concentration can result in some side effects, such as decrease of white blood cells and liver damage. Therefore, it is significant for receiving optimal clinical therapeutic efficacy to monitor imatinib plasma concentration, adjust imatinib dosage timely and keep imatinib plasma concentration in effective and safe range.

Adult ; Antineoplastic Agents ; administration & dosage ; pharmacokinetics ; Benzamides ; Combined Modality Therapy ; Cross-Sectional Studies ; Female ; Gastrectomy ; Gastrointestinal Stromal Tumors ; drug therapy ; surgery ; Humans ; Imatinib Mesylate ; administration & dosage ; pharmacokinetics ; Male ; Middle Aged ; Piperazines ; Pyrimidines ; Tandem Mass Spectrometry

OBJECTIVETo assess the efficacy and safety of Wuji Powder (WP) and a small dose aripiprazole in treatment of antipsychotic drug-induced phlegm dampness type amenorrhea.

METHODSSeventy female schizophrenic patients with antipsychotic drug-induced galactorrhea-amenorrhea syndrome (GAS) were recruited and randomly assigned to the treatment group and the control group, 35 in each group. All patients received antipsychotic drug therapy. Patients in the treatment group additionally took WP, while those in the control group took aripiprazole (at the daily dose of 5 mg, once daily). The therapeutic course for all was 4 weeks. Prolactin levels and obesity indices[body weight, waist aircumstance, body mass index (BMI) and waist-hit ratio (WHR)] were determined before and after treatment. The efficacy was evaluated.

RESULTSThe treatment course was completed in 95.71% of patients. The total effective rate of the 33 patients of the treatment group was 93.94% (31/33), while it was 91.18% (31/34) in the 34 patients of the control group. There was no difference in the total effective rate between the two groups (P > 0.05). Prolactin levels in both group after treatment were significantly lower than those of the baseline (P < 0.01). There was no significant difference in prolactin levels between the two groups after treatment (P > 0.05). Compared with before treatment, body weight, BMI, waist circumstance, and waist-hip ratio obviously decreased after treatment, showing significant difference when compared with the control group (P < 0.05). There was no significant difference in body weight, BMI, waist circumstance, and waist-hip ratio in the control group between before and after treatment (P > 0.05).

CONCLUSIONSBoth WP and aripiprazole could lower high prolactin levels of schizophrenics with phlegm dampness type amenorrhea. They showed equivalent efficacy. But WP showed more obvious effect in reducing obesity indices.

Aged ; Amenorrhea ; drug therapy ; Antipsychotic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Aripiprazole ; Body Mass Index ; Body Weight ; Drug Therapy, Combination ; methods ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Galactorrhea ; drug therapy ; Humans ; Obesity ; Piperazines ; administration & dosage ; adverse effects ; therapeutic use ; Quinolones ; administration & dosage ; adverse effects ; therapeutic use ; Waist-Hip Ratio

OBJECTIVETo investigate the role of imatinib in induction therapy for newly diagnosed adult patients with Philadephia chromosome-positive acute lymphoblastic leukemia (Ph⁺ALL), as well as the status of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in the treatment of adult Ph⁺ ALL in imatinib era.

METHODSRetrospectively analyzed 97 newly diagnosed adult Ph⁺ ALL patients from 2005 to 2013. According to whether administrated imatinib in the induction therapy and the administrating duration (≥3 d) , they were divided into imatinib (n=37) and non-imatinib group (n=60), and the former group was further divided into early-use (n=26) and late-use imatinib groups (n=11) (bounded by the fourteenth day of induction chemotherapy). We compared the overall response rate (ORR) and the negative rate of BCR-ABL fusion gene in patients who achieved complete remission (CR) or CR with incomplete recovery of blood cells (CRi) among the three groups at the end of the first induction therapy. There were 44 cases underwent allo-HSCT (transplant group) and 33 cases only adopted imatinib-based chemotherapy (non-transplant group) in 77 patients who administrated imatinib as a maintenance therapy, we further compared the incidences of overall survival (OS) , disease-free survival (DFS), relapse and nonrelapse mortality (NRM) between the two groups; and dynamically monitor polymerase chain reaction (PCR) negativity of patients who were in CR1 state before transplant (n=34) at the following timepoints of achieving CR or CRi, the first consolidation therapy, beginning the pretreatment of transplant and attaining hematopoietic reconstruction after transplant.

RESULTSAfter the first induction therapy, the ORR of imatinib group was significantly higher than of non-imatinib group (97.3%, 72.9% respectively, P=0.002), but early-use and late-use imatinib groups had no statistical significance in ORR (100% , 90.9% respectively, P=0.297); the rate of negativity of imatinib and non- imatinib groups were 20.0% and 0 respectively (P=0.041) in patients who achieved CR or CRi. The negative rate of patients in CR1 state before transplant attained 20.8%, 42.3%, 51.8%, 76.8%, respectively at the previously described 4 timepoints. And the differences between the fourth and the third, the third and the first timepiont all reached statistical significance (P=0.044, 0.022, respectively). The 5-year OS of transplant and non- transplant groups showed statistical difference (47.0%, 28.0% respectively, P=0.016), also for 5-year DFS (P=0.001) and the cumulative rate of relapse (P=0.000) of the former surpassing the latter; the cumulative rate of NRM between these two groups had no statistical significance (P=0.370).

CONCLUSIONConventional induction chemotherapy in combination with imatinib in the first induction therapy of adult Ph⁺ ALL, not only improved the rate of hematologic remission, also the rate of molecular response. Imatinib used as a consolidation and maintenance therapy after remission, and allo-HSCT scheduled as soon as possible improved the prognosis.

Adolescent ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Benzamides ; administration & dosage ; therapeutic use ; Disease-Free Survival ; Female ; Hematopoietic Stem Cell Transplantation ; Humans ; Imatinib Mesylate ; Male ; Middle Aged ; Philadelphia Chromosome ; Piperazines ; administration & dosage ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; therapy ; Protein Kinase Inhibitors ; administration & dosage ; therapeutic use ; Pyrimidines ; administration & dosage ; therapeutic use ; Retrospective Studies ; Transplantation, Homologous ; Treatment Outcome ; Young Adult

This study was aimed to evaluate the efficacy and safety of imatinib in the treatment of patients with adult Ph chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). A total of 32 diagnosed adult Ph(+)ALL patients from July 2007 to February 2014 in our hospital were retrospectively analyzed and were divided into two groups: imatinib plus chemotherapy group and traditional chemotherapy group. The differences between two groups were analysed in disease-free survival time (DFS), overall survival time (OS) and toxicity. The G banding technigue was used to analyse the karyotype, and the flow cytometry was applyed to detect the immune markers on surface of cells. The results showed that all patients expressed B cell and hematopietic stem/progenitor cell immune markers, out of them 21 patients (65.6%) were with myeloid antigens, 27 patients with simple Ph (+) phenotype and 5 patients with additional chromosome abnormality. The DFS and OS of the imatinib group were statistically longer than those of the traditional chemotherapy group (14.3 ± 4.7 months vs 10.7 ± 3.8 months) (P < 0.05) and 22.6 ± 6.8 months vs 10.7 ± 3.8 months) (P < 0.05)). There was no significant difference in toxic effects between two groups (P > 0.05)). It is concluded that the all cases of adult Ph(+)ALL are with B cell phenotype and express hematopietic stem/progenitor cell antigen. They often accompanied by expression of myeloid antigens and additonal chromosome abnormality in genetics. The combination of imatinib with chemotherapy can prolong remission time and survival time for patients of non-hematopietic stem cell transplantation on the basis of no notably increasing the toxic effects.
Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Benzamides ; administration & dosage ; Disease-Free Survival ; Humans ; Imatinib Mesylate ; Philadelphia Chromosome ; Piperazines ; administration & dosage ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy ; genetics ; Pyrimidines ; administration & dosage ; Retrospective Studies ; Treatment Outcome

Imatinib has been recognized as the frontline therapy drug in chronic myeloid leukemia (CML), however, only limited patients could achieve complete molecular remission (CMR). Recent clinical and basic proofs indicated an improved treatment outcome by the combination of interferon and Imatinib. This study was purposed to evaluated systematically the efficacy and safety of interferon plus Imatinib in patients with CML. Data from relative clinical trials were from clinical trial of gov and Cochrane Collaboration. A comprehensive literature search was performed from data bases such as pubMed and EM. The results indicated that 7 clinical trials and 12 research papers met the criteria enrolled in study, included 697 cases in total. The combination group had higher complete cytogenetic remission (CCgR) rate than imatinib alone at 6 months (58% vs 42%; P = 0.0001) and 12 months (74% vs 68%; P = 0.004). The major molecular remission (MMR) rate was also higher in the combination group at 6 months (58% vs 34%; P = 0.0001) and 12 months (66% vs 47%; P < 0.0001). Furthermore, compared with single drug, the combination group had superior CMR rate at 6 months (13% vs 2%; P = 0.0002) and 12 months (14% vs 5%; P = 0.0009). The major adverse effects of combination therapy were rash, asthenia, edema and musculoskeletal events, and combination therapy was more prone to inducing neutropenia, thrombocytopenia and mild anemia. It is concluded that compared with Imatinib alone, the combination of interferon and Imatinib has better clinical efficacy in treating CML with earlier cytogenetic and molecular remission. It is also a safe therapy in spite of slightly weaker tolerance than single drug therapy.
Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Benzamides ; administration & dosage ; adverse effects ; Humans ; Imatinib Mesylate ; Interferons ; administration & dosage ; adverse effects ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; drug therapy ; Piperazines ; administration & dosage ; adverse effects ; Pyrimidines ; administration & dosage ; adverse effects ; Treatment Outcome

No abstract available.
Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Benzamides/therapeutic use ; Bone Marrow Examination ; Chemoradiotherapy ; Cyclophosphamide/administration & dosage ; Doxorubicin/administration & dosage ; Humans ; Karyotyping ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/*diagnosis/drug therapy/genetics/pathology ; Lymphoma, Large B-Cell, Diffuse/*diagnosis/pathology/therapy ; Male ; *Neoplasms, Second Primary ; Piperazines/therapeutic use ; Positron-Emission Tomography ; Prednisolone/administration & dosage ; Protein Kinase Inhibitors/therapeutic use ; Pyrimidines/therapeutic use ; Time Factors ; Tomography, X-Ray Computed ; Treatment Outcome ; Vincristine/administration & dosage ; Whole Body Imaging/methods

Administration, Inhalation ; Drug Therapy, Combination ; Female ; Hernias, Diaphragmatic, Congenital ; drug therapy ; Humans ; Infant, Newborn ; Male ; Nitric Oxide ; administration & dosage ; Piperazines ; administration & dosage ; Purines ; administration & dosage ; Sildenafil Citrate ; Sulfones ; administration & dosage

OBJECTIVETo evaluate the recurrence-free survival (RFS) and safety of imatinib adjuvant therapy with longer treatment duration in patients undergoing complete resection of localized primary gastrointestinal stromal tumor (GIST).

METHODSClinical and follow-up data of 101 GIST patients between March 2004 and May 2009 with intermediate or high recurrence risk receiving imatinib adjuvant treatment and more than 3 years follow-up time in Peking University Cancer Hospital were retrospectively analyzed. Imatinib adjuvant treatment: 3 patients discontinued less than 1 year imatinib treatment because of adverse events; 24, 21 and 18 patients discontinued imatinib after 1 year, 2 years, and 3 years treatment; 8 patients received 3 years adjuvant treatment and were ongoing; 27 patients received more than 4 years imatinib adjuvant treatment.

RESULTSThe median follow-up time was 60 months (95%CI:57.9-62.1). Nineteen patients had GIST recurrence, of whom recurrence happened during imatinib adjuvant therapy in 5 patients and after imatinib treatment in 14 patients. The median period from imatinib stopping to recurrence was 12.0 months (95%CI:9.6-14.4). Patients with recurrent GIST achieved tumor control after imatinib resumption. RFS of patients (n=53) with ≥3 years imatinib treatment duration was higher than that of patients (n=48) with <3 years imatinib duration (93.9% vs. 68.0%, P<0.01). In addition, prolonged adjuvant imatinib duration did not significantly increase the adverse events related to treatment (P>0.05).

CONCLUSIONSProlonged adjuvant imatinib duration may further improve RFS rate further in patients with intermediate or high risk of recurrence after complete tumor resection without increased adverse events.

Adult ; Aged ; Benzamides ; administration & dosage ; therapeutic use ; Chemotherapy, Adjuvant ; Disease-Free Survival ; Female ; Follow-Up Studies ; Gastrointestinal Neoplasms ; drug therapy ; Gastrointestinal Stromal Tumors ; drug therapy ; Humans ; Imatinib Mesylate ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Piperazines ; administration & dosage ; therapeutic use ; Pyrimidines ; administration & dosage ; therapeutic use ; Retrospective Studies ; Treatment Outcome