paclitaxel

carboplatin

paclitaxel

carboplatin

BEV

Therapeutic effect of bevacizumab combined with paclitaxel and carboplatin on recurrent ovarian cancer. To observe the clinical efficacy and safety of bevacizumab (BEV) combined with paclitaxel on recurrent ovarian cancer. ### methods A total of 164 patients with recurrent ovarian cancer were selected and randomly divided into two groups : experimental group ( n=82 , BEV + paclitaxel + carboplatin ) and control group ( n=82 , paclitaxel + carboplatin ) . The clinical therapeutic effects including objective response rate (ORR), complete response (CR) rate, partial response (PR) rate, stable disease (SD), progressive disease (PD), progression free survival (PFS) and overall survival (OS) were evaluated, together with the adverse clinical reactions and improvement of quality of life (QoL). Immunohistochemistry was used to detect the expression of phosphate and tension homology deleted on chromosome ten (PTEN). ### results The PFS, OS and ORR of patients in the experimental group were significantly higher than those in the control group (p<0.05). In addition, the incidence rates of allergy, gastrointestinal reactions and leukopenia were significantly lower in the experimental group compared with those in the control group (p<0.05). There was no significant difference in QoL score between the two groups before treatment (p>0.05). However, after treatment, the QoL score in the experimental group was increased significantly compared with the control group (p<0.05). Moreover, the expression of PTEN in PR, SD and PD patients was lower, with significant difference between the two groups (p<0.05). ### conclusion The clinical therapeutic effect of BEV combined with paclitaxel in patients with recurrent ovarian cancer was improved, suggesting it might be beneficial for the treatment of ovarian cancer.


thalidomide

vincristine

prednisone

Successful treatment of an adult with Kasabach-Merritt syndrome using thalidomide , vincristine , and prednisone . Kasabach-Merritt syndrome is a rare disease that mainly occurs in infants and adolescents. It usually manifests as disseminated intravascular coagulation and severe bleeding, and is associated with high mortality. However, its low incidence and clinical rarity in adults mean that there is currently no well-verified treatment regimen for this disease. We report on an effective novel therapeutic regimen in a patient with Kasabach-Merritt syndrome. ### methods A woman with Kasabach-Merritt syndrome presented with a recurrent subcutaneous mass and disseminated intravascular coagulation, and was treated with prednisone, vincristine and thalidomide. ### results This treatment regimen successfully resolved the patient's symptoms, with tumor regression. The patient remained disease-free after 6 years of follow-up. ### conclusions prednisone combined with vincristine and thalidomide may be an effective treatment for Kasabach-Merritt syndrome, but further studies are needed to verify the use of this regimen.


sirolimus

rapamycin

cyclosporine

Superiority of sirolimus ( rapamycin ) over cyclosporine in augmenting allograft and xenograft survival in mice treated with antilymphocyte serum and donor-specific bone marrow . sirolimus is a potent immunosuppressive agent with great therapeutic potential. The objective of our study was to evaluate the efficacy of sirolimus versus cyclosporine in augmenting the unresponsiveness induced by an antilymphocyte serum (ALS)/donor-specific bone marrow (BM)-based regimen across three levels of histoincompatibility: class I and II disparate (DBA/2 to B6AF1), complete mismatch (AKR to C57BL/6), and xenograft (ACI rat to B6AF1). ### methods Full-thickness skin grafts were taken from donors and placed on recipients in standard fashion. Seven groups of recipient mice (n=10-28) received various combinations of the following treatment protocols: sirolimus, 1.5 mg/kg (3.0 mg/kg for xenografts) every other day from day 0 to day 12; cyclosporine, 50 mg/kg every other day from day 10 through 22; ALS, 0.5 ml on days -1 and 2 for allografts and days -1, 2, and 4 for xenografts; and BM, 25 million donor-specific cells IV on day 7. ### results The administration of ALS or ALS/BM resulted in modest but significant prolongation of skin graft survival in all combinations tested. cyclosporine combined with ALS or ALS/BM significantly extended allograft survival compared with ALS or ALS/BM alone (P<0.05) but had no effect on xenograft survival. In contrast, the combination of sirolimus with ALS or ALS/BM resulted in a two- to threefold increase in allograft survival and over a fourfold increase in xenograft survival when compared with the comparable cyclosporine-based regimen. Additionally, lymphocytes isolated from class I and II incompatible mice with skin grafts surviving >100 days demonstrated markedly reduced interleukin 2 and interferon-gamma secretion in response to irradiated donor-specific lymphocytes in culture. ### conclusions In the regimens tested, sirolimus was superior to cyclosporine in augmenting donor BM-induced skin graft prolongation in ALS-treated mice across all levels of histoincompatibility.


Fludarabine

Cytarabine

Idarubicin

Gemtuzumab-Ozogamicin

Profiling of drug-metabolizing enzymes/transporters in CD33 + acute myeloid leukemia patients treated with Gemtuzumab-Ozogamicin and Fludarabine , Cytarabine and Idarubicin . Genetic heterogeneity in drug-metabolizing enzyme/transporter (DMET) genes affects specific drug-related cancer phenotypes. To investigate the relationships between genetic variation and response to treatment in acute myeloid leukemia (AML), we genotyped 1931 variants on DMET genes in 94 CD33-positive AML patients enrolled in a phase III multicenter clinical trial combining Gemtuzumab-ozogamicin (GO) with fludarabine-cytarabine-idarubicin (FLAI) regimen, with the DMET Plus platform. Two ADH1A variants showed statistically significant differences (odds ratio (OR)=5.68, P=0.0006; OR=5.35, P=0.0009) in allele frequencies between patients in complete/partial remission and patients without response, two substitutions on CYP2E1 (OR=0.13, P=0.001; OR=0.09, P=0.003) and one on SLCO1B1 (OR=4.68, P=0.002) were found to differently influence liver toxicity, and two nucleotide changes on SULTB1 and SLC22A12 genes correlated with response to GO (OR=0.24, P=0.0009; OR=2.75, P=0.0029). Genetic variants were thus found for the first time to be potentially associated with differential response and toxicity in AML patients treated with a combination of GO-FLAI regimen.


evolocumab

alirocumab

Treatment Strategy for Dyslipidemia in Cardiovascular Disease Prevention: Focus on Old and New Drugs. Prevention and treatment of dyslipidemia should be considered as an integral part of individual cardiovascular prevention interventions, which should be addressed primarily to those at higher risk who benefit most. To date, statins remain the first-choice therapy, as they have been shown to reduce the risk of major vascular events by lowering low-density lipoprotein cholesterol (LDL-C). However, due to adherence to statin therapy or statin resistance, many patients do not reach LDL-C target levels. ezetimibe, fibrates, and nicotinic acid represent the second-choice drugs to be used in combination with statins if lipid targets cannot be reached. In addition , anti-PCSK9 drugs ( evolocumab and alirocumab ) provide an effective solution for patients with familial hypercholesterolemia ( FH ) and statin intolerance at very high cardiovascular risk . Recently, studies demonstrated the effects of two novel lipid-lowering agents (lomitapide and mipomersen) for the management of homozygous FH by decreasing LDL-C values and reducing cardiovascular events. However, the costs for these new therapies made the cost-effectiveness debate more complicated.


Gefitinib

Pemetrexed

[A randomized clinical study of Gefitinib and pemetrexed as second line therapy for advanced non-squamous non-small cell lung cancer]. gefitinib and pemetrexed are drugs used as second-line therapy for advanced non-small cell lung cancer (NSCLC), although studies comparing the two drugs are limited. The aim of this study is to explore the effects, safety, and quality of life (QoL) of gefitinib and pemetrexed on patients with advanced non-squamous NSCLC. ### methods Forty-six advanced non-squamous NSCLC patients who failed to first-line therapy were randomly divided into two groups with 23 patients each, one using oral gefitinib (gefitinib group) and the other using intravenous injection pemetrexed (pemetrexed group). The effects, safety, and QoL were determined and analyzed. ### results For the pemetrexed group, objective response rate (ORR) was 13.0% (3/23), disease control rate (DCR) was 30.4% (7/23), and median progression-free survival (mPFS) was 3.1 months. In the gefitinib group, ORR was 17.3% (4/23), DCR was 39.1% (9/23), and mPFS was 4.4 months. Compared with the pemetrexed group, the ORR, DCR, and mPFS in the gefitinib group exhibited no statistical significance (P>0.05). Furthermore, the most common toxicities in the pemetrexed group were neutropenia (n=9, 39.13%) and fatigue (n=8, 34.78%), whereas those in the in gefitinib group were skin rash (n=8, 34.78%) and diarrhea (n=4, 17.39%). Compared with baseline, the QoL improved in both groups but to different degrees. Likewise , emotional , functional well-being , and QoL aspects specifically related to lung cancer were better improved in the Gefitinib group than in the Pemetrexed group ( P<0.05 ) . ### conclusions The effects of pemetrexed and gefitinib as second line therapy were similar, although with different AEs. Both drugs could improve the QoL, but gefitinib showed better overall results than pemetrexed.


anakinra

methylprednisolone

Anakinra combined with methylprednisolone in patients with severe COVID-19 pneumonia and hyperinflammation: an observational cohort study. Immunomodulants have been proposed to mitigate SARS-Cov-2-induced cytokine storm, which drives acute respiratory distress syndrome in COVID-19. ### objective To determine efficacy and safety of the association of IL-1 receptor antagonist anakinra plus methylprednisolone in severe COVID-19 pneumonia with hyperinflammation . ### methods Secondary analysis of prospective observational cohort studies at an Italian tertiary health-care facility. COVID-19 patients consecutively hospitalized (02/25/2020 to 03/30/2020), with hyperinflammation (ferritin ≥1000ng/mL and/or C-reactive protein >10mg/dL) and respiratory failure (oxygen therapy from 0.4 FiO2 Venturi mask to invasive mechanical ventilation) were evaluated to investigate the effect of high-dose anakinra plus methylprednisolone on survival. Patients were followed from study inclusion to day 28 or death. Crude and adjusted (sex, age, baseline PaO ### results 120 COVID-19 patients with hyperinflammation (median age 62 years, 80.0% males, median PaO ### conclusions Treatment with anakinra plus methylprednisolone may be a valid therapeutic option in COVID-19 patients with hyperinflammation and respiratory failure, also on mechanical ventilation. Randomized, controlled trials including use of either agent alone are needed to confirm these results.


Li

imipramine

desipramine

imipramine

Effects of lithium on alterations of pharmacokinetics of imipramine and on the related changes of monoamines in rat brain. Rats were given chronically i.p. imipramine (20 mg/kg), LiCl (1 mg/kg) or both drugs to examine the effects of lithium (Li) on the alterations of imipramine pharmacokinetics in the whole brain and on the imipramine-related changes of norepinephrine (NE) and serotonin (5-HT) levels in the brain. When rats were given Li for 3 days , followed by a single injection of imipramine , the concentrations of desipramine in the brain and serum were higher than those in the vehicle-treated rat , although the imipramine concentrations in both tissues did not differ in Li- and in vehicle-treated rats . In rats receiving both drugs for 10 days, the steady state levels of imipramine and desipramine in the brain were the same as those in the vehicle-treated rats but the steady state level of desipramine was reached earlier with Li treatments presumably because of the enhanced demethylation of imipramine. Consequently, the desipramine-dependent alterations of NE and 3-methoxy-4-hydroxyphenylglycol levels in the brain appeared to be induced earlier and more markedly when Li was given simultaneously. As the 5-hydroxyindole acetic acid (5-HIAA) levels were elevated in the brains of Li-treated rats and reduced in brains of imipramine-treated rats as compared with the level in vehicle-treated rats, the 5-HIAA level in rats receiving both drugs was equivalent to that in vehicle-treated rats.


ipilimumab

dacarbazine

ipilimumab

A population-based study of the treatment effect of first-line ipilimumab for metastatic or unresectable melanoma. ipilimumab is an anti-CTLA4 monoclonal antibody with demonstrated efficacy for metastatic melanoma in randomized controlled trials, including in the first-line setting. Population-based outcomes directly compared with historic chemotherapy treatment in metastatic or unresectable melanoma are lacking. Using population-based data from the province of Ontario , the benefit of first-line ipilimumab was estimated by comparing outcomes of patients treated with first-line dacarbazine over the period 2007 - 2009 with patients treated over the period 2010 - 2015 with first-line ipilimumab . Cutaneous and noncutaneous cases were included. The administrative data set utilized was high-dimensional; meaning, there was a large number of variables relative to the sample size. To adjust for important confounders among the many available variables, we utilized a double-selection method, a modified machine learning algorithm to extract the important variables that were related to both survival times and treatment usage. Time-dependent treatment modeling was utilized. Among the 2793 melanoma patients receiving palliative treatment (systemic therapy, surgery, or radiation) in Ontario (2007-2015), there were 289 patients treated with first-line ipilimumab (2010-2015) and 175 patients treated with first-line dacarbazine (2007-2009). For first-line ipilimumab, the adjusted hazard ratio compared with dacarbazine for overall survival (OS) was 0.63 (95% confidence interval: 0.47-0.84) with a 1-year survival of 46.5 versus 18.9% with dacarbazine. In subgroup analysis, ipilimumab was associated with improved OS across groups (age, sex, comorbidity, income quintile, previous interferon). First-line ipilimumab was found to have a significant OS benefit compared with historical controls in a population including those patients not routinely included in clinical trials. The treatment effect was similar to randomized controlled trials, suggesting a meaningful benefit when utilized in a population-based setting.


tamoxifen

bromocriptine

[Bromocriptine and tamoxifen--a new therapeutic approach in suppression-resistant prolactin-secreting adenomas].  In the present study the combination of tamoxifen and bromocriptine was tried for the suppression of prolactin in prolactin secreting adenomas which were resistant to suppression with bromoergocriptine alone . 10 women under treatment with 2.5-10 mg of parlodel (bromocriptine) for pituitary tumours of various sizes were additionally treated with tamoxifen 10-20 mg. (nolvadex) daily. Two patients had a previous incomplete resection for chromophobe adenomas. The other patients refused operation. Two women were also studied who did not tolerate a bromoergocriptine therapy because of side effects. In 6 of the 10 women with combination treatment a satisfactory suppression of the prolactin was observed. Four women were cleared of their amenorrhoea and galactorrhoea. One woman conceived. One woman lost her frigidity. Three women, among those the two with severe side effects from bromoergocriptine, tolerated the combined treatment well. Four women showed no success with the combined treatment. The effectiveness of the combined treatment was not correlated with the size of the tumour nor the clinical or biochemical baseline. The results lead to the conclusion that tamoxifen is capable of improving the suppression of prolactin or render the adenomas suppressible in a large number of cases.


thalidomide

dexamethasone

Refractory plasmablastic type myeloma with multiple extramedullary plasmacytomas and massive myelomatous effusion: remarkable response with a combination of thalidomide and dexamethasone. A 74-year-old man with multiple myeloma was refractory to melphalan/prednisolone (MP), high-dose dexamethasone and VAD chemotherapy. He had the following poor prognostic factors: 1) multiple extramedullary plasmacytomas, 2) massive myelomatous effusion, 3) increasing immature myeloma cells with plasmablastic morphology, and 4) predominance of MPC1-CD49e-CD45+ phenotype immature myeloma cells. Combination therapy with thalidomide and dexamethasone resulted in a rapid response and a partial remission despite his multiple poor prognostic factors. The present case suggests that combination therapy with thalidomide and dexamethasone is still an alternative treatment regimen for resistant extramedullary plasmacytoma with a plasmablastic morphology .


doxorubicin

cisplatin

docetaxel

cisplatin

paclitaxel

carboplatin

Effect of Taxane Plus Platinum Regimens vs Doxorubicin Plus Cisplatin as Adjuvant Chemotherapy for Endometrial Cancer at a High Risk of Progression: A Randomized Clinical Trial. The efficacy of taxane plus platinum regimens has been demonstrated for advanced or recurrent endometrial cancer; however, it has not been assessed in postoperative adjuvant chemotherapy for endometrial cancer. ### objective To evaluate the clinical benefit of taxane plus platinum compared with standard doxorubicin plus cisplatin as postoperative adjuvant chemotherapy in endometrial cancer. ### Design Setting And Participants In this multicenter, open-label, phase 3 randomized clinical trial, patients with endometrial cancer at high-risk stage I or II or stage III or IV that did not extend beyond the abdominal cavity and had 2 cm or greater residual tumor were included from 118 institutions in Japan from November 24, 2006, to January 7, 2011. Data was analyzed from March 15, 2017, to June 30, 2017. ### interventions Eligible patients were randomly assigned (1:1:1) to receive 6 cycles of doxorubicin, 60 mg/m2, plus cisplatin, 50 mg/m2, on day 1; docetaxel, 70 mg/m2, plus cisplatin, 60 mg/m2, on day 1; or paclitaxel, 180 mg/m2, plus carboplatin (area under the curve, 6.0 mg/mL × min) on day 1 every 3 weeks. ### Main Outcomes And Measures The primary end point was progression-free survival. Secondary end points were overall survival, occurrence of adverse events, tolerability, and status of lymph node dissection. ### results Among 788 eligible patients , the median ( SD ) age was 59 ( 22 - 74 ) years ; 263 patients were assigned to doxorubicin plus cisplatin treatment , 263 patients to docetaxel plus cisplatin treatment , and 262 patients to paclitaxel plus carboplatin treatment . The number of patients who did not complete 6 cycles was 53 (20.1%) for the doxorubicin plus cisplatin group, 45 (17.1%) for the docetaxel plus cisplatin group, and 63 (24.0%) for the paclitaxel plus carboplatin group. Tolerability of these regimens were not statistically different. After a median follow-up period of 7 years, there was no statistical difference of progression-free survival (doxorubicin plus cisplatin, 191; docetaxel plus cisplatin, 208; paclitaxel plus carboplatin, 187; P = .12) or overall survival (doxorubicin plus cisplatin, 217; docetaxel plus cisplatin, 223; paclitaxel plus carboplatin, 215; P = .67) among the 3 groups. The 5-year progression-free survival rate was 73.3% for the doxorubicin plus cisplatin group, 79.0% for the docetaxel plus cisplatin group, and 73.9% for the paclitaxel plus carboplatin group, while the 5-year overall survival rates were 82.7%, 88.1%, and 86.1%, respectively. ### Conclusions And Relevance There was no significant difference of survival among patients receiving doxorubicin plus cisplatin, docetaxel plus cisplatin, or paclitaxel plus carboplatin as postoperative adjuvant chemotherapy for endometrial cancer. Because each regimen showed adequate tolerability but different toxic effects, taxane plus platinum regimens may be a reasonable alternative to treatment with doxorubicin plus cisplatin. ### Trial Registration UMIN-CTR identifier: UMIN000000522.