DOCSLIB.ORG

Original Article the Role of Low-Dose Decitabine Combined With

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Original Article the Role of Low-Dose Decitabine Combined With Int J Clin Exp Med 2019;12(4):4273-4279 www.ijcem.com /ISSN:1940-5901/IJCEM0075188 Original Article The role of low-dose decitabine combined with chemotherapy in the treatment of recurrent and refractory gastric cancer: a single-center, single-arm clinical study Yan Zhang, Qinggong Yuan, Gang Cao, Junhui Li, Wenbin Yang Department of General Surgery, Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shanxi, China Received February 28, 2018; Accepted October 25, 2018; Epub April 15, 2019; Published April 30, 2019 Abstract: Low-dose decitabine is a safe drug which can inhibit DNMT activity to promote tumor cell apoptosis with- out inducing cell death. This study investigated the clinical efficacy of low-dose decitabine combined with chemo- therapy on the treatment of recurrent and refractory gastric cancer. A total of 227 patients with refractory gastric cancer were retrospective analyzed, including 127 patients treated by low-dose decitabine combined with chemo- therapy drugs (observation group) and 100 cases treated by chemotherapy alone (control group). CD4+, CD8+, and CD4+/CD8+ proportion in peripheral blood lymphocytes were measured by ELISA. Adverse reactions were evaluated by the common toxicity classification criteria according to WHO. The disease control rate (83%) and median survival time (10 months) in observation group were significantly higher than those in control group (P < 0.05). CD3+ showed no obvious changes between before and after treatment (P > 0.05). However, CD4+ and CD4+/CD8+ proportion in both groups were significantly increased after treatment (P < 0.05). Compared with control, CD4+ and CD4+/CD8+ proportion were significantly increased in observation group after treatment (P < 0.05). The incidence of adverse reactions in observation group was markedly lower than that in control group (P < 0.05). The partial remission rates were 47.2% and 43.0%, whereas the disease control rates were 87.4% and 81.0% in observation group and control group, respectively. The application of low-dose decitabine combined with chemotherapy can improve the clinical efficacy, enhance immune function, while reduce the incidence of adverse reactions in patients with refractory gastric cancer. Keywords: Low dose, decitabine, combined chemotherapy, tegafur, refractory gastric cancer Introduction therapy is better than monotherapy [3]. Tradi- tional treatments, including chemotherapy, ra- Gastric cancer is one of most common malig- diotherapy, and surgery, have achieved efficacy nant tumors around the world with a high inci- in a variety of solid tumors and hematologic dence and mortality in China [1]. The best treat- malignancies. However, most patients ultima- ment approach for gastric cancer is surgical tely develop resistance to these therapies and resection. However, because of its occult onset more than 90% of cancer patients died of re- and changeable symptoms, more than 50% of current and metastatic disease. Taking into patients have progressed at the time of being account the defects of traditional therapies in diagnosed and missed the best period of radi- the treatment of refractory solid tumors relapse, cal surgery. There are 50-60% of patients with new therapy is urgently required to improve the recurrence in situ or metastasis within two status [4]. Decitabine has been used in clinic years after radical gastrectomy even in early for more than 10 years with high safety. It is a stage [2]. For patients with refractory gastric cytosine mimics and DNA methyltransferase cancer, systemic chemotherapy-based compre- (DNMT) inhibitor that can silent gene expres- hensive treatment is an important method, and sion by inhibiting DNA methylation through clinical data show that the combined chemo- incorporating into DNA double-strand [5]. De- Low-dose decitabine combined with chemotherapy in refractory gastric cancer citabine has showed good therapeutic effects tegafur capsule orally after the meal at 60 mg/ on MDS, CML, and other hematological malig- m2 for twice a day on the 6th-7th day. nancies. However, its prospect in the treat- ment of solid tumors has not been fully explor- The two therapies were repeated every three ed [6]. Low dose of decitabine can inhibit DNMT weeks. Electrocardiography and hepatorenal activity without inducing cell death. Decitabine function were monitored to prevent potential can activate the expression of tumor suppres- adverse reaction. sor genes, cell cycle regulatory genes, and Observation index other silencing genes to promote tumor cell apoptosis or inhibit cell proliferation [7]. In this All patients underwent at least 2 cycles of study, we initially conducted one-arm clinical chemotherapy. trial of metastatic and refractory pancreatic cancer/colorectal cancer/gastric cancer to eva- Curative effect index luate the efficacy and safety of decitabine. Me- anwhile, it may provide basis to establish stan- According to the RECIST1.1 standard, the treat- dard epigenetic treatment program. ment effect was divided into complete remis- sion, partial remission, stability, and progress. Patients and methods The total effective rate = (complete remission + partial remission)/total population, disease Clinical information control rate = (total population - progress)/total population. The survival time of two groups A total of 227 gastric cancer patients (patho- was followed up to calculate the median sur- logically confirmed and inoperable squamous vival time. Recent evaluation criteria were di- cell carcinoma and adenocarcinoma) in our vided into disease progression (PD), partial hospital from April 2015 to October 2017 we- response (PR), complete remission (CR), and re enrolled, including 127 patients treated with stable condition (SD). RR = (CR + PR)/all cases low-dose decitabine combined with chemother- ×100%. Disease control rate = (CR + PR + SD)/ apy as observation group and 100 patients all cases ×100%. The progression-free survival treated with simple chemotherapy as control was defined as the time from treatment to dis- group. All patients were found lesions, and ease progression. heart, liver and kidney functions were normal before chemotherapy. There were no significant Immune index differences between the two groups in terms of age, sex and pathological classification. Peripheral blood was extracted before and Inclusion criteria: ① meet the diagnostic crite- after treatment to detect CD3+ (Human CD3D ria of squamous cell carcinoma and adenocar- ELISA Kit (CLIA) - LS-F29277, LifeSpan Bio- cinoma that cannot afford surgery and was Sciences, Inc.), CD4+ (Human CD4 ELISA Kit suitable for chemotherapy; ② age 25 - 60 (Sandwich ELISA) - LS-F6263, LifeSpan Bio- years; ③ no chemotherapy contraindications; Sciences, Inc.) and CD8+ (Human CD8 ELISA ④ sign the informed consent. Exclusion crite- Kit (Sandwich ELISA) - LS-F22885, LifeSpan ria: ① extensive metastases of gastric cancer; BioSciences, Inc.) using commercial ELISA kits ② severe liver, kidney, heart diseases or coagu- according to manufacturer’s instructions. lation disorders; ③ poor compliance; ④ exis- tence of mental illness. This study was approved Adverse reaction by the ethics committee and all the subjects had signed informed consent. The adverse reaction during the chemotherapy was observed and graded into I-IV according to Treatment method WHO [8]. Control: The subjects received tegafur capsule Statistical analysis orally after the meal at 80 mg/m2 for twice a day. All data were analyzed by SPSS 19.0 software. The measurement data were presented as Observation group mean ± standard deviation (SD) and compared by student t test, while the enumeration data The subjects received intravenous infusion of were compared by chi-square test. P < 0.05 decitabine at 10 mg/d on the 1st-5th day and was considered as statistical significance. 4274 Int J Clin Exp Med 2019;12(4):4273-4279 Low-dose decitabine combined with chemotherapy in refractory gastric cancer Table 1. Overall effective rate, disease control rate, and median survival observation group after time comparison treatment (P < 0.05) Overall effective Disease control Median survival (Table 2; Supplement- Group rate/% rate/% time/month ary Table 1). Control (n = 100) 27 51 8 Adverse reaction com- Observation group (n = 127) 41 83 10 parison P 0.378 0.036 0.02 The adverse reactions in observation group -1 Table 2. Lymphocytes changes comparison (x ± s, g·L ) were all in degree I-III, Group CD3+ CD4+ CD8+ CD4+/CD8+ which did not affect the Control treatment. In control Before treatment 60.37 ± 6.48 27.13 ± 5.06 23.92 ± 5.09 0.93 ± 1.12 group, 3 cases suffer- After treatment 62.93 ± 5.87 34.02 ± 4.26* 24.03 ± 4.81 1.28 ± 0.22* ed from degree IV alo- Observation group pecia and were reliev- ed after symptomatic Before treatment 61.26 ± 6.03 28.05 ± 4.72 23.40 ± 5.28 0.93 ± 1.06 treatment. The others *,# *,# After treatment 62.84 ± 5.27 39.33 ± 4.21 25.81 ± 4.92 1.48 ± 0.42 were in degree I-III. The * # P < 0.05, compared with before treatment in the same group; P < 0.05, compared with incidence of adverse re- after treatment in the control group. actions in observation group was markedly lo- Results wer than that in control group except nausea, vomiting, and liver damage (P < 0.05) (Table 3). Short-term and long-term curative effect com- parison Curative effect comparison Among 100 patients in control group, 3 cases The mean duration of chemotherapy was 3.3 were completely relieved, 24 were partially months in observation group and 3.1 months relieved, 24 were stable, and 49 were progres- in control group (P = 0.037). The partial remis- sive. The overall response rate was 27% and sion rates were 47.2% and 43.0%, whereas the the median survival time was 8 months. Of disease control rates were 87.4% and 81.0% in the 127 patients in observation group, 5 cases observation group and control group, respec- were completely relieved, 47 cases were par- tively (Table 4). tially relieved, 53 cases were stable, and 22 cases were progress. The overall response rate Overall survival rate was 41% and the median survival time was 10 months.
Load more

Recommended publications
  • (DAC) Followed by Clofarabine, Idarubicin, and Cytarabine (CIA) in Acute Leukemia 2012-1064
    2012-1064 September 02, 2014 Page 1 Protocol Page Phase I/II Study of Decitabine (DAC) followed by Clofarabine, Idarubicin, and Cytarabine (CIA) in Acute Leukemia 2012-1064 Core Protocol Information Short Title Decitabine followed by Clofarabine, Idarubicin, and Cytarabine in Acute Leukemia Study Chair: Nitin Jain Additional Contact: Allison Pike Jeannice Y. Theriot Leukemia Protocol Review Group Department: Leukemia Phone: 713-745-6080 Unit: 428 Full Title: Phase I/II Study of Decitabine (DAC) followed by Clofarabine, Idarubicin, and Cytarabine (CIA) in Acute Leukemia Protocol Type: Standard Protocol Protocol Phase: Phase I/Phase II Version Status: Terminated 01/12/2018 Version: 12 Submitted by: Jeannice Y. Theriot--4/26/2017 2:13:38 PM OPR Action: Accepted by: Melinda E. Gordon -- 5/1/2017 7:55:15 AM Which Committee will review this protocol? The Clinical Research Committee - (CRC) 2012-1064 September 02, 2014 Page 2 Protocol Body Phase I/II Study of Decitabine (DAC) followed by Clofarabine, Idarubicin, and Cytarabine (CIA) in Acute Leukemia 1. OBJECTIVES Phase I Primary: To determine the maximal tolerated dose (MTD) of clofarabine to be used in portion II of the study Phase II Primary: To determine the response rate of the DAC-CIA regimen Secondary: A) To determine the toxicity of the combination regimen B) To determine the disease-free survival (DFS) and overall survival (OS) rates 2. RATIONALE 2.1 Acute Myelogenous Leukemia Acute myelogenous leukemia (AML) is the most common acute leukemia in adults. It is estimated that 13,780 men and women will be diagnosed with and 10,200 men and women will die of acute myeloid leukemia in the year 2012.1 AML is a disease with a poor prognosis with a 5-year survival of only around 30%.2,3 Certain subgroups of AML have a particularly worse Page 1 of 34 outcome such as patients with relapsed and/or refractory AML and AML arising from antecedent myelodysplastic syndrome (MDS) or myeloproliferative neoplasms (MPNs).
    [Show full text]
  • Azacytidine Sensitizes Acute Myeloid Leukemia Cells to Arsenic Trioxide By
    Chau et al. Journal of Hematology & Oncology (2015) 8:46 DOI 10.1186/s13045-015-0143-3 JOURNAL OF HEMATOLOGY & ONCOLOGY RESEARCH ARTICLE Open Access Azacytidine sensitizes acute myeloid leukemia cells to arsenic trioxide by up-regulating the arsenic transporter aquaglyceroporin 9 David Chau1†, Karen Ng1†, Thomas Sau-Yan Chan1, Yuen-Yee Cheng1,3, Bonnie Fong2, Sidney Tam2, Yok-Lam Kwong1 and Eric Tse1* Abstract Background: The therapeutic efficacy of arsenic trioxide (As2O3) in acute myeloid leukemia (AML) is modest, which is partly related to its limited intracellular uptake into the leukemic cells. As2O3 enters cells via the transmembrane protein aquaglyceroporin 9 (AQP9). Azacytidine, a demethylating agent that is approved for the treatment of AML, has been shown to have synergistic effect with As2O3. We tested the hypothesis that azacytidine might up-regulate AQP9 and enhances As2O3-mediated cytotoxicity in AML. Methods: Arsenic-induced cytotoxicity, the expression of AQP9, and the intracellular uptake of As2O3 were determined in AML cell lines and primary AML cells with or without azacytidine pre-treatment. The mechanism of AQP9 up-regulation was then investigated by examining the expression of transcription factors for AQP9 gene and the methylation status of their gene promoters. Results: As2O3-induced cytotoxicity in AML cell lines was significantly enhanced after azacytidine pre-treatment as a result of AQP9 up-regulation, leading to increased arsenic uptake and hence intracellular concentration. Blocking AQP9-mediated As2O3 uptake with mercury chloride abrogated the sensitization effect of azacytidine. AQP9 promoter does not contain CpG islands. Instead, azacytidine pre-treatment led to increased expression of HNF1A, a transcription activator of AQP9, through demethylation of HNF1A promoter.
    [Show full text]
  • Decitabine Plus CLAG Chemotherapy As a Bridge to Haploidentical
    Jin et al. BMC Cancer (2019) 19:242 https://doi.org/10.1186/s12885-019-5464-0 CASEREPORT Open Access Decitabine plus CLAG chemotherapy as a bridge to haploidentical transplantation in the setting of acute myeloid leukemia relapse after HLA-matched sibling transplantation: a case report Mengqi Jin, Yongxian Hu, Wenjun Wu, Yi Luo, Yamin Tan, Jian Yu, Aiyun Jin, Luxin Yang, He Huang* and Guoqing Wei* Abstract Background: Patients with relapsed/refractory acute myeloid leukemia after hematopoietic stem cell transplantation (HSCT) have a poor prognosis, with a 2-year survival rate of 14%. The optimal treatment for these patients remains unclear. To treat these patients, we designed a new salvage regimen consisting of decitabine, cladribine, cytarabine, and granulocyte-stimulating factor (D-CLAG). Case presentation: Here, we describe a case of acute monocytic leukemia with a complex karyotype in a 38-year-old female patient who relapsed after her first HSCT, which was performed using a matched sibling donor. The patient did not respond to standard induction chemotherapy and subsequently achieved complete remission with the D-CLAG regimen. No severe hematological or extramedullary toxicity was observed. Subsequently, the patient received a second D-CLAG regimen as a bridge therapy and directly underwent haploidentical related HSCT. Following HSCT, the marrow showed complete hematologic and cytogenetic remission. Currently, 1 year after transplantation, the patient’s general condition remains good. Conclusions: This case suggests that the D-CLAG regimen can be an option for reinduction in relapsed refractory AML patients as a bridge to transplantation. Nevertheless, further research will be required in the future as this report describes only a single case.
    [Show full text]
  • Comparison Between 5-Day Decitabine and 7-Day Azacitidine For
    www.nature.com/scientificreports OPEN Comparison between 5-day decitabine and 7-day azacitidine for lower-risk myelodysplastic syndromes with poor prognostic features: a retrospective multicentre cohort study Byung-Hyun Lee 1, Ka-Won Kang 1, Min Ji Jeon2, Eun Sang Yu2, Dae Sik Kim2, Hojoon Choi 3, Se Ryeon Lee3, Hwa Jung Sung3, Byung Soo Kim1, Chul Won Choi2* & Yong Park1* Numerous studies have analysed the clinical efcacies of hypomethylating agents (HMAs) in patients with myelodysplastic syndromes (MDS). However, reports that compare the two HMAs, decitabine and azacitidine, in patients with lower-risk (low and intermediate-1) MDS are limited. We compared 5-day decitabine and 7-day azacitidine regimens in terms of treatment responses, survival outcomes, and adverse events in patients with lower-risk MDS with poor prognostic features. The overall response rates (ORRs) were 67.2% and 44.0% in the patients treated with decitabine and azacitidine, respectively (P = 0.014). While the median progression-free survival (PFS) was signifcantly better in the patients treated with decitabine than in those treated with azacitidine (P = 0.019), no signifcant diferences in event-free and overall survival rates were observed between the two groups. Multivariate analysis revealed that compared with azacitidine treatment, decitabine treatment is signifcantly associated with a higher ORR (P = 0.026) and longer PFS (P = 0.037). No signifcant diferences were observed in the incidence of grade 3 or higher haematologic adverse events in response to the two HMAs. In conclusion, in lower-risk MDS, especially with poor prognostic features, ORR and PFS were signifcantly better with 5-day decitabine treatment than with 7-day azacitidine treatment, with comparable safety.
    [Show full text]
  • A Phase II Study of Omacetaxine (OM) in Patients with Intermediate-1 and Higher Risk Myelodysplastic Syndrome (MDS) Post Hypomethylating Agent (HMA) Failure 2013-0870
    Protocol Page A Phase II Study of Omacetaxine (OM) in Patients with Intermediate-1 and Higher Risk Myelodysplastic Syndrome (MDS) post Hypomethylating Agent (HMA) Failure 2013-0870 Core Protocol Information Short Title Omacetaxine in Patients with Intermediate-1 and Higher Risk MDS post HMA Failure Study Chair: Elias Jabbour Additional Contact: Jhinelle L. Graham Vicky H. Zoeller Leukemia Protocol Review Group Additional Memo Recipients: Recipients List OPR Recipients (for OPR use only) None Study Staff Recipients None Department: Leukemia Phone: 713-792-4764 Unit: 0428 Full Title: A Phase II Study of Omacetaxine (OM) in Patients with Intermediate-1 and Higher Risk Myelodysplastic Syndrome (MDS) post Hypomethylating Agent (HMA) Failure Protocol Type: Standard Protocol Protocol Phase: Phase II Version Status: Activated -- Closed to new patient entry as of 08/05/2018 Version: 08 Document Status: Saved as "Final" Submitted by: Vicky H. Zoeller--9/11/2017 12:24:33 PM OPR Action: Accepted by: Margaret Okoloise -- 9/14/2017 12:09:50 PM Which Committee will review this protocol? The Clinical Research Committee - (CRC) Protocol Body 2013-0870 March 6, 2017 1 A Phase II Study of Omacetaxine (OM) in Patients with Intermediate-1 and Higher Risk Myelodysplastic Syndrome (MDS) post Hypomethylating Agent (HMA) Failure 2013-0870 March 6, 2017 2 Table of Contents 1.0 Objectives .................................................................................................. 3 2.0 Background ..............................................................................................
    [Show full text]
  • View – 2003;22(12):3164 74
    Qin et al. Clinical Epigenetics (2015) 7:97 DOI 10.1186/s13148-015-0131-z RESEARCH Open Access Epigenetic synergy between decitabine and platinum derivatives Taichun Qin1†, Jiali Si1†, Noël J-M Raynal1,4, Xiaodan Wang3, Vazganush Gharibyan1, Saira Ahmed1, Xin Hu1, Chunlei Jin1, Yue Lu1,2, Jingmin Shu1, Marcos RH Estecio1,2, Jaroslav Jelinek1,4 and Jean-Pierre J. Issa1,4* Abstract Background: Aberrant epigenetic silencing of tumor suppressor genes has been recognized as a driving force in cancer. Epigenetic drugs such as the DNA methylation inhibitor decitabine reactivate genes and are effective in myeloid leukemia, but resistance often develops and efficacy in solid tumors is limited. To improve their clinical efficacy, we searched among approved anti-cancer drugs for an epigenetic synergistic combination with decitabine. Results: We used the YB5 cell line, a clonal derivative of the SW48 colon cancer cell line that contains a single copy of a hypermethylated cytomegalovirus (CMV) promoter driving green fluorescent protein (GFP) to screen for drug-induced gene reactivation and synergy with decitabine. None of the 16 anti-cancer drugs tested had effects on their own. However, in combination with decitabine, platinum compounds showed striking synergy in activating GFP. This was dose dependent, observed both in concurrent and sequential combinations, and also seen with other alkylating agents. Clinically achievable concentrations of carboplatin at (25 μM) and decitabine reactivated GFP in 28 % of the YB5 cells as compared to 15 % with decitabine alone. Epigenetic synergy was also seen at endogenously hypermethylated tumor suppressor genes such as MLH1 and PDLIM4. Genome- wide studies showed that reactivation of hypermethylated genes by the combination was significantly better than that induced by decitabine alone or carboplatin alone.
    [Show full text]
  • Sorafenib and Omacetaxine Mepesuccinate As a Safe and Effective Treatment for Acute Myeloid Leukemia Carrying Internal Tandem Du
    Original Article Sorafenib and Omacetaxine Mepesuccinate as a Safe and Effective Treatment for Acute Myeloid Leukemia Carrying Internal Tandem Duplication of Fms-Like Tyrosine Kinase 3 Chunxiao Zhang, MSc1; Stephen S. Y. Lam, MBBS, PhD1; Garret M. K. Leung, MBBS1; Sze-Pui Tsui, MSc2; Ning Yang, PhD1; Nelson K. L. Ng, PhD1; Ho-Wan Ip, MBBS2; Chun-Hang Au, PhD3; Tsun-Leung Chan, PhD3; Edmond S. K. Ma, MBBS3; Sze-Fai Yip, MBBS4; Harold K. K. Lee, MBChB5; June S. M. Lau, MBChB6; Tsan-Hei Luk, MBChB6; Wa Li, MBChB7; Yok-Lam Kwong, MD 1; and Anskar Y. H. Leung, MD, PhD 1 BACKGROUND: Omacetaxine mepesuccinate (OME) has antileukemic effects against acute myeloid leukemia (AML) carrying an internal tandem duplication of Fms-like tyrosine kinase 3 (FLT3-ITD). A phase 2 clinical trial was conducted to evaluate a combina- tion treatment of sorafenib and omacetaxine mepesuccinate (SOME). METHODS: Relapsed or refractory (R/R) or newly diagnosed patients were treated with sorafenib (200-400 mg twice daily) and OME (2 mg daily) for 7 (first course) or 5 days (second course on- ward) every 21 days until disease progression or allogeneic hematopoietic stem cell transplantation (HSCT). The primary endpoint was composite complete remission, which was defined as complete remission (CR) plus complete remission with incomplete hematologic recovery (CRi). Secondary endpoints were leukemia-free survival (LFS) and overall survival (OS). RESULTS: Thirty-nine R/R patients and 5 newly diagnosed patients were recruited. Among the R/R patients, 28 achieved CR or CRi. Two patients showed partial remission, and 9 patients did not respond.
    [Show full text]
  • Decitabine, a DNA Methyltransferase Inhibitor, Reduces P-Glycoprotein
    ANTICANCER RESEARCH 32: 4439-4444 (2012) Decitabine, a DNA Methyltransferase Inhibitor, Reduces P-Glycoprotein mRNA and Protein Expressions and Increases Drug Sensitivity in Drug-resistant MOLT4 and Jurkat Cell Lines KENJI ONDA, RIEKO SUZUKI, SACHIKO TANAKA, HIROKAZU OGA, KITARO OKA and TOSHIHIKO HIRANO Department of Clinical Pharmacology, Tokyo University of Pharmacy and Life Sciences, Tokyo, Japan Abstract. Multidrug resistance (MDR) is a major clinical There have been many studies on the effect of DNA de- obstacle in the treatment of several cancers including methylation agents on cancer cells and drug-resistant cells hematological malignancies and solid tumors. The ATP- (4-6). However, in order to explore the possibility of binding cassette transporter B1 (ABCB1) gene and its product, epigenetic modifiers in clinical settings, more research is P-glycoprotein (P-gp), is one molecule that is involved in drug required to characterize the association of the effect of DNA resistance. Here we report on the effect of decitabine (5-aza- de-methylation agents with the drug-resistant features of 2’-deoxycytidine), an inhibitor of DNA methyltransferase, on several types of cancer cell. In the current study, we ABCB1 mRNA and P-gp expressions in drug-resistant MOLT4 investigated the effect of decitabine treatment on the drug and Jurkat cells. We found that decitabine treatment reduced sensitivity of two drug-resistant hematopoietic cell lines, ABCB1 mRNA and P-gp expressions in MOLT4/daunorubicin- MOLT4/resistant to daunorubicin (DNR) and Jurkat/resistant resistant and Jurkat/doxorubicin-resistant cells. The decrease to doxorubicin (DOX), established in our laboratory by in the expression of ABCB1 mRNA and P-gp was accompanied culturing cells with stepwise concentrations of daunorubicine by increased sensitivity to anticancer drugs in both drug- and doxorubicine, respectively (7).
    [Show full text]
  • Standard Oncology Criteria C16154-A
    Prior Authorization Criteria Standard Oncology Criteria Policy Number: C16154-A CRITERIA EFFECTIVE DATES: ORIGINAL EFFECTIVE DATE LAST REVIEWED DATE NEXT REVIEW DATE DUE BEFORE 03/2016 12/2/2020 1/26/2022 HCPCS CODING TYPE OF CRITERIA LAST P&T APPROVAL/VERSION N/A RxPA Q1 2021 20210127C16154-A PRODUCTS AFFECTED: See dosage forms DRUG CLASS: Antineoplastic ROUTE OF ADMINISTRATION: Variable per drug PLACE OF SERVICE: Retail Pharmacy, Specialty Pharmacy, Buy and Bill- please refer to specialty pharmacy list by drug AVAILABLE DOSAGE FORMS: Abraxane (paclitaxel protein-bound) Cabometyx (cabozantinib) Erwinaze (asparaginase) Actimmune (interferon gamma-1b) Calquence (acalbrutinib) Erwinia (chrysantemi) Adriamycin (doxorubicin) Campath (alemtuzumab) Ethyol (amifostine) Adrucil (fluorouracil) Camptosar (irinotecan) Etopophos (etoposide phosphate) Afinitor (everolimus) Caprelsa (vandetanib) Evomela (melphalan) Alecensa (alectinib) Casodex (bicalutamide) Fareston (toremifene) Alimta (pemetrexed disodium) Cerubidine (danorubicin) Farydak (panbinostat) Aliqopa (copanlisib) Clolar (clofarabine) Faslodex (fulvestrant) Alkeran (melphalan) Cometriq (cabozantinib) Femara (letrozole) Alunbrig (brigatinib) Copiktra (duvelisib) Firmagon (degarelix) Arimidex (anastrozole) Cosmegen (dactinomycin) Floxuridine Aromasin (exemestane) Cotellic (cobimetinib) Fludara (fludarbine) Arranon (nelarabine) Cyramza (ramucirumab) Folotyn (pralatrexate) Arzerra (ofatumumab) Cytosar-U (cytarabine) Fusilev (levoleucovorin) Asparlas (calaspargase pegol-mknl Cytoxan (cyclophosphamide)
    [Show full text]
  • IRO RECO OCT 0 2 Al
    Protocol 9713.00 IRO RECO OCT 0 2 al FRED HUTCHINSON CANCER RESEARCH CENTER UNIVERSITY OF WASHINGTON SCHOOL OF MEDICINE Current version: 10/02/2018 Previous version: 5/3/18 Phase 1/2 Study of Concurrent Decitabine in Combination with G-CSF, Cladribine, Cytarabine, and Mitoxantrone (G-CLAM) in Adults with Newly Diagnosed Acute Myeloid Leukemia (AML) or High-Risk Myelodysplastic Syndromes (MDS) Principal Investigator: Roland B. Walter, MD PhD MS, Associate Member, Fred Hutchinson Cancer Research Center; Associate Professor, UW (206-667-3599) Sub-Investigators at Fred Hutch/UW: • Mary-Beth Percival, MD, Assistant Member, Fred Hutchinson Cancer Research Center; Assistant Professor, UW (206-288-1320) • Pamela S. Becker, MD PhD, Associate Member, Fred Hutchinson Cancer Research Center; Professor, UW (206-543-3360) • Paul C. Hendrie, MD PhD Clinical Associate Professor, UW (206-288-6366) • Anna B. Halpern, MD, Senior Hematology/Oncology Fellow, UW (206-314-5944) • Elihu H. Estey, MD, Member, Fred Hutchinson Cancer Research Center; Professor, UW (206-288-7176) Biostatistician: • Megan Othus, PhD, Associate Member, Fred Hutchinson Cancer Research Center (206- 667-5749) Emergency Phone (24 hours): For non-transplant patients: Call the paging operator at the University of Washington Medical Center at 206-598-6190, and ask for the Fellow on call for Hematology/Oncology. For transplant patients: Call the 8NE front desk at the University of Washington Medical Center at 206-598-8902, and ask for the triaging provider covering the bone marrow transplant service. FHCRC IRB Approval OCT 10 2018 Document Released Date Page 1 of 34 Protocol 9713.00 OVERVIEW OF THE TREATMENT PLAN GCLA RespObse.
    [Show full text]
  • Low-Dose Decitabine for Patients With
    Letters RESEARCH LETTER the decitabine group vs 27.3% in the control group (P = .001). In the treatment group, platelet counts increased signifi- Low-Dose Decitabine for Patients With cantly 4 weeks after decitabine injections (Figure), with a Thrombocytopenia Following Allogeneic median time of 22 days to achieve platelet transfusion- Hematopoietic Stem Cell Transplantation: independence, and maintained until the sixth month, except A Pilot Therapeutic Study for the patient with minor response. Isolated thrombocytopenia after hematopoietic stem cell trans- In bone marrow morphological analysis, patients in both plantation (HSCT) is defined as consistently low platelet counts groups revealed low levels of megakaryocytes at week 0. How- after transplantation, with recovery of all other peripheral blood ever, the significantly increasing megakaryocyte level, espe- cell lines.1 It represents a challenging clinical problem be- cially the “platelet shedding” megakaryocyte, was observed cause it often leads to an increased risk of life-threatening hem- only in decitabine group at week 4 (Figure). Transplantation- orrhage, frequent requirement of platelet transfusions, and ex- related complications (eg, chronic GVHD), antiplatelet anti- tended hospital stays.2 Previous studies have demonstrated bodies, and T-cell subsets did not noticeably change after that decitabine, a hypomethylating agent, can increase plate- decitabine treatment. No clinically significant myelosuppres- let counts by enhancing platelet release and megakaryocyte sion, febrile neutropenia, or nonhematologic toxic effects were maturation in mice.3 Herein, we report a pilot study showing observed during the study period. efficacy of decitabine in patients with isolated thrombocyto- penia post-HSCT. Discussion | Our study shows a very encouraging result of decitabine in increasing peripheral platelets in HSCT recipi- Methods | An open-label study was designed to evaluate ents, with remarkably increased megakaryocyte counts.
    [Show full text]
  • New Combination Drug Regimens Using
    NEW COMBINATION DRUG REGIMENS USING HYPOMETHYLATING AGENTS IN TREATING OLDER PATIENTS WITH NEW DIAGNOSIS OF ACUTE MYELOID LEUKEMIA PAVAN TENNETI MD, ANKITH TENNETI, SRINIVASA SANIKOMMU MD LEVINE CANCER INSTITUTE, CHARLOTTE, NC. INTRODUCTION RESULTS TABLE- CDR USING HMA IN OLDER PATIENTS WITH AML • The prognosis of acute myeloid leukemia(AML) in • In seven phase I/II studies, decitabine(n=500) was combined with gemcitabine ozagamicin older patients is inherently poor. (n=40, CR/CRi =45%, mOS= 7 m), cladribine and low dose cytarabine(n=118, CR/CRi= 68%, mOS =13.8 m), vadastuximab talirine(n=53, CR/CRi=70%, mOS=11.3 m) and selinexor(n=5, • In older patients not fit for intensive chemotherapy, CR/CRi= 80%). complete response/complete response with incomplete hematologic response(CR/CRi) and • Three studies compared outcomes of CDR involving decitabine with altrans retinoic median overall survival(mOS) has been evaluated acid(ATRA)(n=93, ORR=21.9% vs 13.5%, p=0.06; mOS= 8.2 m vs 5.1 m, p=0.006) or with hypomethylating agents(HMA) including talacotuzumab(CR/CRi= 15% vs 11%, p=0.44; mOS= 5.36 m vs 7.26 m, p=0.78) or azacytidine(AZA)(CR/CRi=18-27.8%, mOS=10.4- bortezomib(CR/Cri= 39% vs 38%, p=0.91, mOS=9.3 m vs 8.9,p=0.18) to decitabine alone. 24.5 m) and decitabine(CR/CRi= 18-47%, mOS= 7- 7.8 m). • Cladribine and low dose cytarabine with decitabine in patients with adverse cytogenetics showed a decent CR/CRi of 50%, mOS= 10.5 months.
    [Show full text]