DOCSLIB.ORG

Inflammatory High-Risk Breast Cancer

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Bone Marrow Transplantation (2000) 26, 51–59 2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt High-dose busulfan, melphalan and thiotepa as consolidation for non- inflammatory high-risk breast cancer F Gutierrez-Delgado, LA Holmberg, H Hooper, FR Appelbaum, RB Livingston, RT Maziarz, P Weiden, S Rivkin, P Montgomery, K Kawahara and W Bensinger Fred Hutchinson Cancer Research, University of Washington and Puget Sound Oncology Consortium, Seattle, WA, USA Summary: disease,3–7 and stage III disease8,9 have a probability of disease-free survival (DFS) at 5 years of 13 to 45% which The purpose of this study was to evaluate the toxicity falls to 10 to 30% at 10 years. and efficacy of high-dose busulfan, melphalan and thi- The experimental and clinical observations suggesting a otepa (Bu/Mel/TT) in patients with high-risk non- significant dose–response relationship in metastatic and pri- inflammatory breast cancer defined as stage II disease mary breast cancer10–14 have encouraged the evaluation of у10 lymph nodes (n = 52) or stage III (n = 69), and high-dose chemotherapy supported with autologous stem prognostic factors for treatment outcome. One hundred cell infusion (HDC/ASCI) as treatment for breast cancer. and twenty-one patients (median age, 46 years) were While a wide range of regimens and trials have evaluated treated with high-dose Bu (12 mg/kg), Mel (100 mg/m2) this approach in metastatic disease, relatively few trials and TT (500 mg/m2) (HDC) followed by autologous stem have investigated the therapeutic potential of HDC/ASCI cell infusion (ASCI). One hundred patients were in high-risk non-inflammatory breast cancer.15–22 The use of initially treated with surgery followed by standard adju- STAMP-I (cyclophosphamide, carmustine and cisplatin),15 vant chemotherapy prior to HDC/ASCI. Twenty-one STAMP-V (cyclophosphamide, thiotepa and patients with stage III disease had inoperable tumors at carboplatin),18–21 CAVP/CCVP (cyclophosphamide, etopo- diagnosis and were treated with neoadjuvant chemo- side and either cisplatin or doxorubicin)16 and CEP therapy and surgery before HDC/ASCI. Transplant- (cyclophosphamide, etoposide and cisplatin)22 has resulted related mortality was 6%. The probabilities of event- in event-free survival (EFS) probabilities ranging from 0.48 free survival (EFS) at 3 and 5 years (median follow-up to 0.72 at 3.5 years after diagnosis16,17,19,21 or from the first of 36 months) from transplant were, for all patients: day of adjuvant chemotherapy15,18,20,22 in patients with 0.62–0.60; stage II: 0.71–0.67: stage III: 0.55–0.55 (for high-risk non-inflammatory breast cancer. stage III adjuvant and neoadjuvant groups: 0.60–0.60 Studies carried out at the Fred Hutchinson Cancer and 0.42–0.42, respectively). Multivariate analysis did Research Center (FHCRC) have evaluated a regimen of not identify variables associated with poor outcome. The busulfan, melphalan and thiotepa, three drugs with efficacy of Bu/Mel/TT is similar to other HDC regimens observed activity in patients with hematologic malignancies reported for patients with high-risk non-inflammatory and patients with breast cancer. The rationale for use of breast cancer. Bu/Mel/TT has high activity in stage II this regimen is based on the recognized activity of mel- disease and a moderate benefit in stage III operable phalan and thiotepa as single agents in the treatment of tumors. Bone Marrow Transplantation (2000) 26, 51–59. breast cancer and the cytotoxic effect observed in meta- Keywords: high-dose chemotherapy; breast cancer; static breast cancer when high doses of busulfan are com- PBSC; busulfan; melphalan; thiotepa bined with cyclophosphamide.23–25 The busulfan, mel- phalan and thiotepa regimen has shown high activity in the treatment of patients with metastatic breast cancer.23–25 Bensinger et al25 reported estimated probabilities of EFS at Despite adjuvant chemotherapy at conventional doses, 1.5 years for patients with metastatic responsive and refrac- Ͼ patients with breast cancer who are stage II with 3 posi- tory disease as 0.53 and 0.24, respectively, with this regi- tive axillary lymph nodes or stage III at diagnosis have a men. The aim of this study was to evaluate the toxicity 1–9 high risk of relapse. At 5 years, the best reported relapse- and efficacy of this regimen in patients with high-risk non- free survival for patients with four to nine metastatic lymph inflammatory breast cancer, as well as to identify the prog- 1 2 nodes is 46–67%; at 10 years, 32–47%. Moreover, the nostic factors which could influence treatment outcome. risk of relapse increases with each additional metastatic lymph node found at surgery. Patients with stage II breast у cancer who have 10 lymph-nodes containing metastatic Patients and methods After obtaining written informed consent, patients were Correspondence: Dr F Gutierrez-Delgado, Fred Hutchinson Cancer Research Center, 1100 Fairview Av North D5–390, PO Box 19024, treated at the FHCRC, the University of Washington or at Seattle, WA 98109–1024, USA hospitals affiliated with the Puget Sound Oncology Consor- Received 11 August 1999; accepted 10 April 2000 tium (PSOC) according to Institutional Review Board High-dose chemotherapy for high-risk breast cancer F Gutierrez-Delgado et al 52 approved protocols of the hospitals where the treatment was Table 1 Patient characteristics administered. Fifty patients were treated at the FHCRC and 71 in member hospitals of PSOC listed in the Appendix. Characteristics Stage The date of the last follow-up for patients in the present II III report was 21 July 1999. Between September 1993 and July 1997, 121 women n 52 69 Age, years, median (range) 47 (27–63) 46 (29–61) with high-risk non-inflammatory breast cancer, defined as Hormone receptor status (%) stage II у10 axillary lymph nodes (n = 52), stage IIIA ER+ PR+ 31 (60) 30 (43) (n = 62) or stage IIIB (n = 7),26 were treated with high-dose ER+ PR− 4 (8) 9 (13) busulfan, melphalan and thiotepa. Patients with stage IIIB ER−/PR− 4 (8) 4 (6) ER−/PR+ 12 (23) 20 (29) inflammatory carcinoma were excluded from this analysis. Unknown 1 (1) 6 (9) Eligibility criteria included age less than 65 years, adequate Number of metastatic lymph nodes, 13 (10–32) 10 (0–35) pulmonary, cardiac, hepatic and renal function and Karnof- median (range) sky score Ͼ70. Hepatitis B surface antigen (HbsAg) and 0–9 (%) 0 30 (44) human immunodeficiency virus serologically positive 10–14 (%) 30 (58) 19 (28) 15–19 (%) 15 (29) 9 (13) patients were excluded. Staging studies included computed Ͼ20 (%) 7 (13) 11 (16) tomography (CT) of chest and abdomen, bone scan and Tumor stage (%) bone marrow aspirations and biopsies. Cranial CT or mag- T1 17 (33) 1 (1) netic resonance imaging (MRI) of the head was performed T2 35 (67) 18 (26) T3 0 48 (70) if clinically indicated. Patients with stage II disease T4 (a) 0 2 (3) underwent modified radical mastectomy or lumpectomy Histology followed by standard-dose doxorubicin-based adjuvant Ductal 45 (87) 55 (80) chemotherapy prior to HDC/ASCI. Initial treatment for Lobular 5 (10) 12 (17) patients with stage III disease was determined by clinical Undifferentiated 2 (3) 2 (3) criteria of operable or inoperable tumors according to Haa- gensen’s classification.27 Patients with stage III disease (a) Extension to chest wall. diagnosed as having operable tumors were initially treated with surgery, followed by standard-dose doxorubicin-based Table 2 Therapy prior to HDC/ASCI adjuvant chemotherapy. Patients with stage III disease who had inoperable tumors received neoadjuvant chemotherapy Therapy Stage followed by surgery. In this study, patients with stage III II III disease were classified into two groups based on conven- tional chemotherapy administered following surgery n 52 69 (adjuvant chemotherapy group) or as initial treatment prior Surgery (%) Modified radical mastectomy 38 (73) 67 (97) to surgery (neoadjuvant chemotherapy group). Segmentectomy and node disection 14 (27) 2 (3) Chemotherapy (%) Doxorubicin-based chemotherapy 52 (100) 68 (99) Patient characteristics Number of cycles, median (range) 4 (3–6) 4 (2–13) Patient characteristics are shown in Table 1. Sixty and 71% Chemotherapy for stage III disease (%) Adjuvant chemotherapy 52 (100) 47 (68) of patients with stage II and stage III disease were younger Neoadjuvant chemotherapy 0 21 (31) than 50 years, respectively. The main differences between Chemotherapy regimen (%) patients with stage III disease beside the initial treatment CAF 30 (58) received were in the hormone receptor and lymph node AC 10 (19) 40 (59) Others: (Abeloff, A+Taxol, CMF)a 12 (23) 19 (28) status. Forty-eight (70%) patients with stage III disease had 9 (13) operable tumors and underwent modified radical mastec- Radiation therapy (%) tomy (n = 47) or lumpectomy (n = 1). Twenty-one (30%) Prior to HDC/ASCI 13 (25) 10 (14) patients were diagnosed as having inoperable tumors, and After HDC/ASCI 34 (65) 56 (81) after diagnostic biopsy, were treated with standard-dose doxorubicin-based induction chemotherapy. Twenty-four aAbeloff regimen13 = cyclophosphamide (C) + doxorubicin (A) + metho- trexate (M) + vincristine + 5-fluorouracil (F). CMF for patients with stage (50%) patients of the adjuvant group were ER and PR hor- II disease. mone receptor positive compared to six (29%) patients of the neoadjuvant group, while 12 (20%) and eight (38%) patients were hormone receptor negative, respectively. The patients. One of the patients with stage III disease had a median number of metastatic lymph nodes for patients who history of idiopathic leukopenia. After mastectomy, she was received adjuvant chemotherapy after surgery was 11 not given adjuvant chemotherapy or radiotherapy and was (range 0–35) and five (range 1–18) for those treated with referred directly for HDC/ASCI using PBSC mobilized neoadjuvant chemotherapy prior to surgery.
Recommended publications
  • ASHP Guidelines on Handling Hazardous Drugs

    ASHP Guidelines on Handling Hazardous Drugs

    132 Drug Distribution and Control: Preparation and Handling–Guidelines ASHP Guidelines on Handling Hazardous Drugs ASHP published its first guidance on hazardous drugs (HDs) Because newer studies have shown that contamination in 1983 as part of the 1983–84 ASHP Practice Spotlight: Safe is widespread in healthcare settings and that more workers Handling of Cytotoxic Drugs.1,2 This was followed by tech- than previously thought are exposed, these guidelines should nical assistance bulletins in 1985 and 1990 and the ASHP be implemented wherever HDs are received, stored, pre- Guidelines on Handling Hazardous Drugs in 2006.3-5 The pared, transported, administered, or disposed.8-11 2006 guidelines were created to harmonize with the National Comprehensive reviews of the literature covering an- Institute for Occupational Safety and Health (NIOSH) Alert: ecdotal and case reports of surface contamination, worker ex- 6,9,12 Preventing Occupational Exposure to Antineoplastic and posure, and risk assessment are available from NIOSH, Other Hazardous Drugs in Health Care Settings issued in the Occupational Safety and Health Administration 13,14 15-20 2004.6 The ASHP 2006 HD guidelines were current to 2005. (OSHA), and individual authors. The primary goal In 2007, the United States Pharmacopeial Convention of this document is to provide recommendations for the safe revised United States Pharmacopeia (USP) chapter 797 handling of HDs. These guidelines represent the research (Pharmaceutical Compounding—Sterile Preparations)7 to and recommendations of many groups and individuals who harmonize with the NIOSH 2004 Alert. It became effective have worked tirelessly over decades to reduce the potential May 1, 2008, establishing many of the NIOSH recommenda harmful effects of HDs on healthcare workers.
  • NOV 1 72010 1.0 Submitter

    NOV 1 72010 1.0 Submitter

    510(k) SUMMARY NOV 1 72010 1.0 Submitter Name Shen Wei (USA) Inc. Street Address 33278 Central Ave., Suite 102 Union City, CA. 94587 Phone No. (510)429-8692 Fax No. (510)487-5347 Date of Summary Prepared: 08/12/10 Prepared by: Albert Li 2.0 Name of the device: Glove Proprietary or Trade Name: Blue and Red with Pearlescent® Pigment, Powder Free Nitrile Examination Gloves with Aloe Vera, Tested for use with Chemotherapy Drugs Common Name: Exam gloves Classification Name: Patient examination glove, Specialty Chemotherapy'(per 21 CFR 880.6250 product code LZC) Classification Information: Class I Nitrile patient examination glove 8OLZC, powder-free and meeting all the requirements of ASTM D 631 9-O0a-05 and is tested with chemotherapy drugs according to ASTM D 6978-05. 3.0 Identification of the Legally Marketed Device: Blue and Red with Pearlescent® Pigment, Powder Free Nitrile Examination Gloves with Aloe Vera Regulatory Class I Nitrile patient examination Product code: 8OLZA 5 10(k): K092411 4.0 Description of the Device: Blue and Red with Pearlescent® Pigment, Powder Free Nitrite Examination Gloves with Aloe Vera, Tested for use with Chemotherapy Drugs meets all the requirements of ASTM D 6978-05, ASTM D63 19-00a(2005) and FDA 21 CFT 880.6250. 5.0 Intended Use of Device: Product: Red with Pearlescent® Pigment, Powder Free Nitrile Examination Gloves with Aloe Vera, Tested for use with Chemotherapy Drugs A disposable device intended for medical purpose that is worn on the examiner's hand to prevent contamination between patient and examiner. This device is single use only.
  • Arsenic Trioxide As a Radiation Sensitizer for 131I-Metaiodobenzylguanidine Therapy: Results of a Phase II Study

    Arsenic Trioxide As a Radiation Sensitizer for 131I-Metaiodobenzylguanidine Therapy: Results of a Phase II Study

    Arsenic Trioxide as a Radiation Sensitizer for 131I-Metaiodobenzylguanidine Therapy: Results of a Phase II Study Shakeel Modak1, Pat Zanzonico2, Jorge A. Carrasquillo3, Brian H. Kushner1, Kim Kramer1, Nai-Kong V. Cheung1, Steven M. Larson3, and Neeta Pandit-Taskar3 1Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York; 2Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York; and 3Molecular Imaging and Therapy Service, Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York sponse rates when compared with historical data with 131I-MIBG Arsenic trioxide has in vitro and in vivo radiosensitizing properties. alone. We hypothesized that arsenic trioxide would enhance the efficacy of Key Words: radiosensitization; neuroblastoma; malignant the targeted radiotherapeutic agent 131I-metaiodobenzylguanidine pheochromocytoma/paraganglioma; MIBG therapy 131 ( I-MIBG) and tested the combination in a phase II clinical trial. J Nucl Med 2016; 57:231–237 Methods: Patients with recurrent or refractory stage 4 neuroblas- DOI: 10.2967/jnumed.115.161752 toma or metastatic paraganglioma/pheochromocytoma (MP) were treated using an institutional review board–approved protocol (Clinicaltrials.gov identifier NCT00107289). The planned treatment was 131I-MIBG (444 or 666 MBq/kg) intravenously on day 1 plus arsenic trioxide (0.15 or 0.25 mg/m2) intravenously on days 6–10 and 13–17. Toxicity was evaluated using National Cancer Institute Common Metaiodobenzylguanidine (MIBG) is a guanethidine analog Toxicity Criteria, version 3.0. Response was assessed by Interna- that is taken up via the noradrenaline transporter by neuroendo- tional Neuroblastoma Response Criteria or (for MP) by changes in crine malignancies arising from sympathetic neuronal precursors 123I-MIBG or PET scans.
  • Busulfan–Melphalan Followed by Autologous Stem Cell

    Busulfan–Melphalan Followed by Autologous Stem Cell

    Bone Marrow Transplantation (2016) 51, 1265–1267 © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved 0268-3369/16 www.nature.com/bmt LETTER TO THE EDITOR Busulfan–Melphalan followed by autologous stem cell transplantation in patients with high-risk neuroblastoma or Ewing sarcoma: an exposed–unexposed study evaluating the clinical impact of the order of drug administration Bone Marrow Transplantation (2016) 51, 1265–1267; doi:10.1038/ survival (OS) was the time from study entry (that is, the first day bmt.2016.109; published online 25 April 2016 of HDC) to death or the last follow-up, whichever occurred first. EFS was the time from study entry to disease progression, a second malignancy, death or the last follow-up, whichever High-dose chemotherapy (HDC) and autologous stem cell occurred first. OS and EFS were estimated using the Kaplan–Meier transplantation (ASCT) have improved the prognosis of high-risk method. Patients from the two treatment groups (Bu–Mel neuroblastoma and metastatic Ewing sarcoma.1,2 The impact of and Mel–Bu) of the same age at diagnosis were matched. the drugs in the HDC regimen was first demonstrated in a The association of the treatment group with toxicity and study performed in the Gustave Roussy Pediatrics Department. efficacy outcomes was assessed using Cox regression models It showed improved survival for patients with stage 4 stratified on matched pairs and adjusted for other confounding neuroblastoma who received a combination of busulfan (Bu) factors, such as the year of diagnosis, VOD prophylaxis and age at and melphalan (Mel).3 These results were confirmed in a diagnosis.
  • An Evaluation of Engraftment, Toxicity and Busulfan Concentration in Children Receiving Bone Marrow Transplantation for Leukemia Or Genetic Disease

    An Evaluation of Engraftment, Toxicity and Busulfan Concentration in Children Receiving Bone Marrow Transplantation for Leukemia Or Genetic Disease

    Bone Marrow Transplantation (2000) 25, 925–930 2000 Macmillan Publishers Ltd All rights reserved 0268–3369/00 $15.00 www.nature.com/bmt An evaluation of engraftment, toxicity and busulfan concentration in children receiving bone marrow transplantation for leukemia or genetic disease AM Bolinger1, AB Zangwill1, JT Slattery2,3, D Glidden4, K DeSantes5, L Heyn6, LJ Risler3, B Bostrom7 and MJ Cowan8 1University of California at San Francisco, Department of Clinical Pharmacy; 2Department of Pharmaceutics, University of Washington; 3Fred Hutchinson Cancer Research Center; 4University of California at San Francisco, Department of Epidemiology and Biostatistics; 5University of Wisconsin, Department of Pediatrics; 6University of California at San Francisco, Department of Nursing; 7University of Minnesota, Department of Pediatrics; and 8University of California at San Francisco, Department of Pediatrics, San Francisco, CA, USA Summary: children exhibit average busulfan steady-state concen- trations (Css) or an area under the curve (AUC) substan- Autologous recovery is a major problem with busulfan tially less than do older children or adults.7–9 The Css corre- as a marrow ablative agent in conditioning children for sponds to the AUC over a dosing interval divided by the allogeneic BMT. Data suggest the average concentration 6 h between doses. The AUC over a dosing interval is equal of busulfan at steady state (Bu Css) is critical for suc- to the AUC from the time the first dose is ingested to infin- cessful engraftment. We prospectively evaluated busul- ity if no subsequent doses are taken. A Css of 900 ng/ml fan pharmacokinetics in 31 children (age 0.6–18 years) is equal to an AUC of 1350 ␮m × min.
  • Wear the Battle Gear That Protects Against 52 Chemotherapy Drugs!

    Wear the Battle Gear That Protects Against 52 Chemotherapy Drugs!

    YOU’RE FIGHTING CANCER. Wear the Battle Gear That Protects Against 52 Chemotherapy Drugs! PURPLE NITRILE-XTRA* Gloves and HALYARD* Procedure Gowns for Chemotherapy Use have been tested It’s 52 vs. You. for resistance to 52 chemotherapy drugs.† Arsenic Trioxide (1 mg/ml) Cyclophosphamide (20 mg/ml) Fludarabine (25 mg/ml) Mitomycin (0.5 mg/ml) Temsirolimus (25 mg/ml) Azacitidine (Vidaza) (25 mg/ml) Cytarabine HCl (100 mg/ml) Fluorouracil (50 mg/ml) Mitoxantrone (2 mg/ml) Trastuzumab (21 mg/ml) Bendamustine (5 mg/ml) Cytovene (10 mg/ml) Fulvestrant (50 mg/ml) Oxaliplatin (2 mg/ml) ThioTEPA (10 mg/ml) Bleomycin Sulfate (15 mg/ml) Dacarbazine (10 mg/ml) Gemcitabine (38 mg/ml) Paclitaxel (6 mg/ml) Topotecan HCl (1 mg/ml) Bortezomib (Velcade) (1 mg/ml) Daunorubicin HCl (5 mg/ml) Idarubicin (1 mg/ml) Paraplatin (10 mg/ml) Triclosan (1 mg/ml) Busulfan (6 mg/ml) Decitabine (5 mg/ml) Ifosfamide (50 mg/ml) Pemetrexed (25 mg/ml) Trisenox (0.1 mg/ml) Carboplatin (10 mg/ml) Docetaxel (10 mg/ml) Irinotecan (20 mg/ml) Pertuzumab (30 mg/ml) Vincrinstine Sulfate (1 mg/ml) Carfilzomib (2 mg/ml) Doxorubicin HCl (2 mg/ml) Mechlorethamine HCl (1 mg/ml) Raltitrexed (0.5 mg/ml) Vinblastine (1 mg/ml) Carmustine (3.3 mg/ml)† Ellence (2 mg/ml) Melphalan (5 mg/ml) Retrovir (10 mg/ml) Vinorelbine (10 mg/ml) Cetuximab (Erbitux) (2 mg/ml) Eribulin Mesylate (0.5 mg/ml) Methotrexate (25 mg/ml) Rituximab (10 mg/ml) Zoledronic Acid (0.8 mg/ml) Cisplatin (1 mg/ml) Etoposide (20 mg/ml) † Testing measured no breakthrough at the Standard Breakthrough Rate of 0.1ug/cm2/minute, up to 240 minutes for gloves and 480 minutes for gowns, except for carmustine.
  • Mitomycin C in the Treatment of Chronic Myelogenous Leukemia

    Mitomycin C in the Treatment of Chronic Myelogenous Leukemia

    Nagoya ]. med. Sci. 29: 317-344, 1967. MITOMYCIN C IN THE TREATMENT OF CHRONIC MYELOGENOUS LEUKEMIA AKIRA HosHINo 1st Department of Internal Medicine Nagoya University School oj Medicine (Director: Prof. Susumu Hibino) SUMMARY Studies made of the treatment with 66 courses of mitomycin C in 28 patients with chronic myelogenous leukemia are reported. The effect of mitomycin C was investigated according to the relation between drug and host factors, comparison with the effects of other agents, and drug resistance. Patients with less hematological and clinical symptoms responded better to mitomycin C therapy. The remission rate of cases treated intravenously with mitomycin C was 93.8% and of cases treated orally with mitomycin C was 72.0%. The remission rate of the total cases (intravenous and oral) treated with mitomycin C was 77.3%. The therapeutic effect of mitomycin C is considered to be equal or be somewhat superior to the effect of busulfan as a result of data on the occurrence of resistance, cross resistance, development of acute blastic crisis and life span. Busulfan was effective in patients resistant to mitomycin C, and mitomycin C did not clinically show cross resistance to alkylating agents. Two patients resist· ant to mitomycin C recovered the sensitivity to mitomycin C after treatment with busulfan or 6-mercaptopurine. Side effects were observed in 39.4% of 66 cases, but severe side effect causing suspension of mitomycin C was rare. I. INTRODUCTION Human leukemia serves as a useful investigative model in which the de­ finite effect of anti-cancer agents can be evaluated quantitatively by factors such as the improvement of hematological findings and clinical symptoms, the remission rate, and the prologation of life span.
  • Standard Oncology Criteria C16154-A

    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)
  • 1 Contents of Online Supporting Information Etable 1. Study

    1 Contents of Online Supporting Information Etable 1. Study

    Contents of Online Supporting Information eTable 1. Study characteristics for trials of intravesical therapy vs. TURBT alone eTable 2. Study characteristics of head to head trials of intravesical therapy eTable 3. Study characteristics of trials comparing dose or duration of a single drug eTable 4. Summary of the evidence eFigure 1. Literature flow diagram eFigure 2. Meta-analysis of doxorubicin versus no intravesical therapy: Risk of recurrence eFigure 3. Meta-analysis of epirubicin versus no intravesical therapy: Risk of recurrence References for the Supplement 1 eTable 1. Study characteristics for trials of intravesical therapy vs. TURBT alone Author, Year Risk of Bias Inclusion Criteria Population Characteristics Intervention Followup Duration Abrams, 19811 Histologically confirmed All characteristics reported for A: Doxorubicin, 50 mg (in 50 6 months for all patients. High superficial bladder tumor; all randomized patients, not mL saline). Single instillation, Recurrent only, with presence the groups analyzed: within 24 hours of TURBT of tumors at both of two Age, mean (years): 72 vs. 68 (n=30). previous endoscopies 12 Male: 70% vs. 79% months and 6 months before Recurrent bladder cancer: B: No adjuvant treatment. entry into trial; Stages Ta or 100% vs. 100% TURBT alone (n=30). T1; Included grades not Ta: 73% vs. 77% specified, but "well" and T1: 27% vs. 23%; "moderate" differentiation included. Akaza, 19872 Histologically proven Age, mean (years): 62.3 vs. A: Doxorubicin, 30 mg (in 30 Maximum (years): 5; Not [Study One] superficial bladder cancer 62.9 vs. 62.9 vs. 62.9 mL saline). Total 8 instillations: reported as median/mean, nor (followup of Niijima, (primary or recurrent).
  • Cardio-Oncology: Basics and Knowing When You Need an Echo

    Cardio-Oncology: Basics and Knowing When You Need an Echo

    1/10/2018 Cardio-oncology: Basics and Knowing When You Need an Echo Vera H. Rigolin, MD, FASE, FACC, FAHA Professor of Medicine Northwestern University Feinberg School of Medicine Medical Director, Echocardiography Laboratory Northwestern Memorial Hospital Chicago, Illinois President, American Society of Echocardiography No Disclosures • Acknowledgement: Nausheen Akhter, MD, Director of the cardio-oncology program at Northwestern 1 1/10/2018 Introduction • The number of cancer therapies have significantly increased • Cancer survival has improved • A number of cancer therapies have cardiotoxic effects Cardiotoxic Syndromes Associated with Chemo Agents associated with LV Agents associated with dysfunction hypertension • Bevacizumab (Avastin) • Anthracylines • Cisplatin • Mitoxanthrone • IL-2 • Cyclophosphamide • Trastuzumab Agents associated with Other toxic effects • Ifosfamide • Tamponade or endomyocardial • All-trans retinoic acid fibrosis (Busulfan) • Hemorrhagic Myocarditis Agents associated with (Cyclophosphamide) ischemia • Bradycardia (Taxol, Thalidomide) • 5-FU • Raynaud’s (Vinblastine) • Cisplatin • Autonomic neurop (Vincristine) • Capecitabine (Xeloda) • Long QT (Arsenic trioxide) • Pulm fibrosis (Bleo) • IL-2 Yeh et al. Circulation 2004 2 1/10/2018 Angiogenesis Inhibitors • Angiogenesis is a key factor for tumor growth and survival. • Angiogenesis inhibitors have shown to improve outcomes in various malignancies • Tumor growth suppression achieved by: – Direct inhibition of VEGF ligand’s ability to target receptor (bevacizumab, ramucirumab, aflibercept) – Small molecules that inhibit tyrosine kinases (sunitinib, sorafenib, pazopanid, vandetanib, vatalanib, cobazantinib, axitinib, regorafenib) Mechanisms of Action of Angiogenic Inhibitors Maurea N et. J Cardiovasc Med 2016;17(suppl):e-19-e26 3 1/10/2018 Odds ratio for adverse cardiac events due to angiogenesis inhibitors Abdel-Qadir H et al. Cancer Treatment Reviews 20178;53:120-127. J Am Soc Echocardiogr2014;27:911-39.
  • Conditioning Regimens Intravenous Busulfan for Allogeneic Hematopoietic Stem Cell Transplantation in Infants: Clinical and Pharmacokinetic Results

    Conditioning Regimens Intravenous Busulfan for Allogeneic Hematopoietic Stem Cell Transplantation in Infants: Clinical and Pharmacokinetic Results

    Bone Marrow Transplantation (2003) 32, 647–651 & 2003 Nature Publishing Group All rights reserved 0268-3369/03 $25.00 www.nature.com/bmt Conditioning Regimens Intravenous busulfan for allogeneic hematopoietic stem cell transplantation in infants: clinical and pharmacokinetic results JH Dalle1, D Wall2, Y Theoret1, M Duval1, L Shaw3, D. Larocque1, C Taylor2, J Gardiner3, MF Vachon1 and MA Champagne1 1Service d’He´matologie et Oncologie Pe´diatrique, Hoˆpital Sainte Justine, Montre´al QC, Canada; 2Methodist Children’s Hospital of South Texas, San Antonio, TX,USA; and 3Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA, USA Summary: tion, very wide inter- and intrapatient systemic exposure is observed with two- to sixfold of coefficient variability. High-dose busulfan is an important component of This wide bioavailability range may be linked to erratic myeloablative regimens. Variable drug exposure may intestinal absorption (7 emesis), variable hepatic metabo- occur following oral administration. Therefore, the use lism, circadianrhythm, geneticpolymorphism of a-glu- of intravenous busulfan has been advocated. Previous tathione-S-transferase, initial diagnosis, previous work has suggested a cumulative dosage of 16 mg/kg for treatment, drug–drug interaction and/or patient age. haematopoietic transplantation in children less than 3 Hepatic and renal clearance mechanisms are generally years of age, but only limited data are available in infants. underdeveloped and inefficient in the neonate, but they Pharmacokinetics of intravanous busulfan administered at may change dramatically in the months following birth. the suggested dosage were studied in 14 infants (median Thus, pharmacokinetically guided dosage adjustment age 4.7 months). Busulfan plasma concentrations were appears mandatory, particularly in children.5,7–12 measured by either GC-MS or HPLC-UV.
  • Induction of Sister Chromatid Exchanges and Chromosomal Aberrations by Busulfan in Philadelphia Chromosome-Positive Chronic Myeloid Leukemia and Normal Bone Marrow1

    Induction of Sister Chromatid Exchanges and Chromosomal Aberrations by Busulfan in Philadelphia Chromosome-Positive Chronic Myeloid Leukemia and Normal Bone Marrow1

    (CANCER RESEARCH 48, 3435-3439, June 15, 1988) Induction of Sister Chromatid Exchanges and Chromosomal Aberrations by Busulfan in Philadelphia Chromosome-positive Chronic Myeloid Leukemia and Normal Bone Marrow1 Reinhard Becher2 and Gabriele Prescher Innere Universitäts-und Poliklinik (Tumorforschung), Westdeutsches Tumorzentrum, Hufelandstrasse 55. 4300 Essen l. Federal Republic of Germany ABSTRACT (5) human tumor cell lines and described a correlation between the sensitivity to chemotherapy measured by the colony-form Cytogenetic effects of busulfan in vitro were studied in normal bone ing efficiency assay and the rate of induced SCE. Furthermore, marrow (nine cases) and Philadelphia chromosome (Ph)-positive cells the clonal heterogeneity of chemotherapy resistance within a (10 cases) of patients with chronic myeloid leukemia. The frequency of single solid tumor was evidenced by different levels of induced chromosome aberrations and sister chromatid exchange (SCE) increased dose dependently. While there were no significant differences between SCE (6). normal and leukemic cells with regard to the induction of chromosome Our intention was to analyze SCE induction by therapeuti- aberrations, the frequency of SCE was significantly lower in Ph-positive cally relevant agents in leukemias. Ph-positive CML was chosen cells than in normal bone marrow. This difference was not only apparent for the study presented here because the leukemic cells can on the basis of the SCE frequency per cell, but also when the SCE easily be distinguished from normal cells by means of the Ph frequency was correlated to the relative chromosome length as shown by chromosome. Secondly, SCE and chromosome breaks in nor the SCE rate per chromosome group.