DOCSLIB.ORG

SFPO and ESOP Recommendations for The

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
SFPO and ESOP Recommendations for The Annales Pharmaceutiques Françaises (2013) 71, 376—389 Disponible en ligne sur www.sciencedirect.com ORIGINAL ARTICLE SFPO and ESOP recommendations for the practical stability of anticancer drugs: An update Mise à jour des recommendations de la SFPO et de l’ESOP pour la stabilité pratique des anticancéreux a,∗ b c d J. Vigneron , A. Astier , R. Trittler , J.D. Hecq , e f g h M. Daouphars , I. Larsson , B. Pourroy , F. Pinguet a Pharmacy, university hospital, rue du Morvan, 54511 Vandœuvre, France b UMR 7054, school of medicine, Henri-Mondor hospital, 94010 Créteil, France c University hospital, Freiburg, Germany d University hospital Mont Godinne, 5530 Yvoir, Belgium e Centre Henri-Becquerel, 76038 Rouen, France f Amgros, Copenhagen, Denmark g Pharmacy, university hospital, 13005 Marseille, France h Val d’Aurelle cancer center, 34298 Montpellier, France Received 20 May 2013; accepted 12 June 2013 Available online 28 August 2013 KEYWORDS Summary The recommandations for the practical stability of anticancer drugs published in Stability; 2010 by the French Society of Hospital Pharmacists (SFPO) and the European Society of Oncology Anticancer drugs; Pharmacists (ESOP) have been updated. Ten new molecules have been included (asparagi- Monoclonal nase, azacitidine, bevacizumab, clofarabine, eribuline mesylate, folinate sodium, levofolinate antibodies; calcium, nelarabine, rituximab, temsirolimus). Dose banding; © 2013 Elsevier Masson SAS. All rights reserved. Stabilis® ∗ Corresponding author. E-mail address: [email protected] (J. Vigneron). 0003-4509/$ — see front matter © 2013 Elsevier Masson SAS. All rights reserved. http://dx.doi.org/10.1016/j.pharma.2013.06.002 SFPO and ESOP recommendations for the practical stability of anticancer drugs 377 MOTS CLÉS Résumé Les recommandations concernant la stabilité pratique des préparations Stabilité ; d’anticancéreux émanant de la Société franc¸aise de pharmacie oncologique (SFPO) et Anticancéreux ; de la Société européenne de pharmacie oncologique (ESOP) parue en 2010 ont été actual- Anticorps isées. Dix nouvelles molécules ont été ajoutées (asparaginase, azacitidine, bevacizumab, monoclonaux ; clofarabine, eribuline mesylate, folinate sodium, levofolinate calcium, nelarabine, rituximab, Dose banding ; temsirolimus) Stabilis® © 2013 Elsevier Masson SAS. Tous droits réservés. Introduction change in chemistry [i.e., peptide mapping] and biological activity [e.g. cytotoxicity on cells, bioassays). Other inter- These recommendations for storage conditions of anticancer esting studies which uses only one or two methods were not drugs are the result of the deliberations of the SFPO (French selected [3,4]. Society for Oncology Pharmacy) stability group. The first For some drugs, interesting results were not selected due edition of the data were published in 2008 by the Cen- to various reasons. The stability of bendamustine was stud- tre national hospitalier d’information sur le médicament, ied by Krämer et al. [5] with a 9 hours stability at room CNHIM — National Information Centre on Hospital Drugs. temperature and a 5 days in the refrigerator. The results The stability group comprised Arnaud P, Astier A, Bellanger of this study published in 1994 were based on the classi- A, Bonan B, Breilh D, Burnel S, Daouphars M, Ferrio AL, cal T90% of the initial concentration. However, today, the Havard L, Helvig A, Husson MC, Pinguet F, Poisson N, Sar- recommendations of the manufacturer [6] are based on the rut B, Vigneron J. These recommendations were adopted as T95% with a 3.5 hours stability at room temperature and the European standard by ESOP in 2010 and published in the 2 days in the refrigerator. These data were in accordance European Journal of Oncology Pharmacy [1]. with the T95% of Krämer et al. We decided to use the rec- A new group with members of SFPO and European hospital ommendation « Follow SPC) ». Moreover, this decision is in pharmacists has updated this work in 2012. This new group accordance with the European guideline for stability studies comprised Alain Astier, Mikaël Daouphars, Frédéric Pinguet, of anticancer drugs [7]. Bertrand Pourroy, Jean Vigneron for SFPO and Jean Daniel For vincristine, the extended stability in polyolefine bags Hecq from Belgium, Iben Larsson from Denmark and Rainer was also demonstrated in polypropylene syringes [8] but Trittler from Germany. the information has not been selected because of the rec- In this updated article, new drugs have been included ommendations of the World Health Organisation [9] who (asparaginase, azacitidine, bevacizumab, clofarabine, recommend to prepare the vinca-alcaloids only in infusion eribuline mesylate, folinate sodium, levofolinate calcium, bags to avoid inadvertent intrathecal injections. nelarabine, rituximab, temsirolimus). Some drugs received Below, we present the new informations and their inter- new informations (cisplatine, docetaxel, fludarabine, oxali- ests in the daily practice. We have separated the long-term platine, vincristine). Three drugs no longer available on the and the short-term stability studies. ‘‘Long-term’’ has been market have been removed from the table: chlormethine, arbitrarily defined as a stability of at least 2 weeks. mitoguazone and pirarubicine. The updated recommendations are presented in Table 1. Long-term stability studies Selection criteria for the articles These studies can be divided into five categories. New informations were selected by using the Stabilis database. For each monograph, the new publications until 2008 have been revised according to a checklist to select The stability of monoclonal antibodies inclusion criteria for the physical and chemical stability. The articles were selected if they brought new informations for The three studies presented here are the first fully validated the daily practice (for example, extended stability for the stability studies according to the ICH guideline Q5C. Several preparation in advance). We decided to include the infor- complementary methods have been used to evaluate the sta- mations presented in posters if the stability study was in bility of rituximab. Various protein characterization methods accordance to our criteria and submitted to publication. were used to determine changes in physicochemical proper- The stability data of simple solutions (one drug in one con- ties of rituximab, including size-exclusion chromatography, tainer) have been selected. The stability of mixtures or of dynamic light scattering, turbidimetry, cation-exchange non-injectable drugs were not in the field of this work. chromatography, second-derivative ultraviolet and infrared Stability studies of monoclonal antibodies carried out spectroscopy, and peptide mapping. Cell culture was used in accordance with the recommendations of ICH Guide- to assess biological stability. lines Q5C [2] were selected. These stability studies use The authors have demonstrated a 6 months stability for at least three complementary methods (study of aggre- the infusions at 1 mg/mL in 0.9% sodium chloride in poly- ® gation [e.g. size exclusion chromatography, turbidimetry], olefine container (Freeflex ) [71]. This long-term stability 378 Table 1 SFPO and ESOP recommendations for the practical stability of anticancer drugs. Recommandations SFPO et ESOP pour la stabilité pratique des anticancéreux. Product Container Vehicle Concentration Recommendations for References storage conditions Alemtuzumab Follow SPC Amifostine Follow SPC ◦ 3 Asparaginase Polypropylene NaCl 0.9% 80 UI/mL 7 days at 2—8 C ◦ ◦ Azacitidine Polypropylene WFI (4 C) 25 mg/mL 23 days at −20 C [10—12] ◦ syringes 5 days at 2—8 C Bendamustine Follow SPC ◦ 1 Bevacizumab Polypropylene NaCl 0.9% 2 to 16 mg/mL 90 days at 4 or 25 C Bleomycin Follow SPC ◦ Bortezomib Glass - NaCl 0.9% Reconstituted: 1 mg/mL 35 days at 2—8 C [13,14] polypropylene syringes ◦ Glass NaCl 0.9% Reconstituted: 2.5 mg/mL 30 days at 2—8 C [15] ◦ Busulfan 2-piece Non-diluted solution: 28 days at 2—8 C or at [16] Never freeze busulfan syringes 6 mg/mL room temperature ◦ ◦ Incompatible with polycarbonate Polypropylene NaCl 0.9% Diluted in administration 19 hours at 2 C—8 C [17] (dimethylacetamide) vehicle: 0.5 mg/mL Protected from light ◦ Glass NaCl 0.9% Diluted in administration 48 hours at 2—8 C vehicle: 0.5 mg/mL ◦ ◦ Polypropylene NaCl 0.9% Diluted in administration 36 hours at 13 C—15 C or glass vehicle: 0.5 mg/mL Protected from light Caelyx Follow SPC ◦ Carboplatin PVC - Dextrose 5% Diluted in administration 84 days at 4 C or 84 days [18—20] ◦ polyethylene vehicle: 0.70—2.15 mg/mL of which 83 days at 4 C and 1 day at room temperature Protected from light Polyethylene - Dextrose 5% Diluted in administration 30 days at room polypropylene vehicle: 3.2 mg/mL temperature J. protected from light Vigneron ◦ Carmustine Glass - Dextrose 5% Diluted in administration 48 hours at 4 C, 2.5 hours [21,22] Never use PVC polyethylene vehicle: 0.2 mg/mL in polyethylene at room Should be protected from light temperature et Protected from light al. SFPO and Table 1 (Continued) ESOP Product Container Vehicle Concentration Recommendations for References storage conditions recommendations ◦ Polyethylene Dextrose 5% Diluted in administration 4 hours at 25 C in the light ◦ vehicle: 0.1—0.5 mg/mL and 48 hours at 4 C ◦ Polyethylene Dextrose 5% Diluted in administration 4 hours at 25 C and ◦ vehicle: 1 mg/mL 24 hours at 4 C Cisplatin Ethyl vinyl NaCl 0.9% Diluted in administration 28 days at room [23—25] for acetate - vehicle: 0.5—0.9 mg/mL temperature polyethylene - 0.1—0.4
Load more

Recommended publications
  • Bevacizumab Plus Fotemustine As First-Line Treatment in Metastatic Melanoma Patients: Clinical Activity and Modulation of Angiogenesis and Lymphangiogenesis Factors
    Published OnlineFirst October 28, 2010; DOI: 10.1158/1078-0432.CCR-10-2363 Clinical Cancer Cancer Therapy: Clinical Research Bevacizumab plus Fotemustine as First-line Treatment in Metastatic Melanoma Patients: Clinical Activity and Modulation of Angiogenesis and Lymphangiogenesis Factors Michele Del Vecchio1, Roberta Mortarini2, Stefania Canova1, Lorenza Di Guardo1, Nicola Pimpinelli3, Mario R. Sertoli4, Davide Bedognetti4, Paola Queirolo5, Paola Morosini6, Tania Perrone7, Emilio Bajetta1, and Andrea Anichini2 Abstract Purpose: To assess the clinical and biological activity of the association of bevacizumab and fotemustine as first-line treatment in advanced melanoma patients. Experimental Design: Previously untreated, metastatic melanoma patients (n ¼ 20) received bevaci- zumab (at 15 mg/kg every 3 weeks) and fotemustine (100 mg/m2 by intravenous administration on days 1, 8, and 15, repeated after 4 weeks) in a multicenter, single-arm, open-label, phase II study. Primary endpoint was the best overall response rate; other endpoints were toxicity, time to progression (TTP), and overall survival (OS). Serum cytokines, angiogenesis, and lymphangiogenesis factors were monitored by multiplex arrays and by in vitro angiogenesis assays. Effects of fotemustine on melanoma cells, in vitro, on vascular endothelial growth factor (VEGF)-C release and apoptosis were assessed by ELISA and flow cytometry, respectively. Results: One complete response, 2 partial responses (PR), and 10 patients with stable disease were observed. TTP and OS were 8.3 and 20.5 months, respectively. Fourteen patients experienced adverse events of toxicity grade 3–4. Serum VEGF-A levels in evaluated patients (n ¼ 15) and overall serum proangiogenic activity were significantly inhibited. A significant reduction in VEGF-C levels was found in several post-versus pretherapy serum samples.
    [Show full text]
  • The New Therapeutic Strategies in Pediatric T-Cell Acute Lymphoblastic Leukemia
    International Journal of Molecular Sciences Review The New Therapeutic Strategies in Pediatric T-Cell Acute Lymphoblastic Leukemia Marta Weronika Lato 1 , Anna Przysucha 1, Sylwia Grosman 1, Joanna Zawitkowska 2 and Monika Lejman 3,* 1 Student Scientific Society, Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland; [email protected] (M.W.L.); [email protected] (A.P.); [email protected] (S.G.) 2 Department of Pediatric Hematology, Oncology and Transplantology, Medical University of Lublin, 20-093 Lublin, Poland; [email protected] 3 Laboratory of Genetic Diagnostics, Medical University of Lublin, 20-093 Lublin, Poland * Correspondence: [email protected] Abstract: Childhood acute lymphoblastic leukemia is a genetically heterogeneous cancer that ac- counts for 10–15% of T-cell acute lymphoblastic leukemia (T-ALL) cases. The T-ALL event-free survival rate (EFS) is 85%. The evaluation of structural and numerical chromosomal changes is important for a comprehensive biological characterization of T-ALL, but there are currently no ge- netic prognostic markers. Despite chemotherapy regimens, steroids, and allogeneic transplantation, relapse is the main problem in children with T-ALL. Due to the development of high-throughput molecular methods, the ability to define subgroups of T-ALL has significantly improved in the last few years. The profiling of the gene expression of T-ALL has led to the identification of T-ALL subgroups, and it is important in determining prognostic factors and choosing an appropriate treatment. Novel therapies targeting molecular aberrations offer promise in achieving better first remission with the Citation: Lato, M.W.; Przysucha, A.; hope of preventing relapse.
    [Show full text]
  • Nelarabine) Injection • Severe Neurologic Reactions Have Been Reported
    HIGHLIGHTS OF PRESCRIBING INFORMATION --------------------- DOSAGE FORMS AND STRENGTHS -------------- These highlights do not include all the information needed to use 250 mg/50 mL (5 mg/mL) vial (3) ARRANON safely and effectively. See full prescribing information for -------------------------------CONTRAINDICATIONS------------------------ ARRANON. None. ----------------------- WARNINGS AND PRECAUTIONS ---------------- ARRANON (nelarabine) Injection • Severe neurologic reactions have been reported. Monitor for signs and Initial U.S. Approval: 2005 symptoms of neurologic toxicity. (5.1) WARNING: NEUROLOGIC ADVERSE REACTIONS • Hematologic Reactions: Complete blood counts including platelets should See full prescribing information for complete boxed warning. be monitored regularly. (5.2) Severe neurologic adverse reactions have been reported with the use of • Fetal harm can occur if administered to a pregnant woman. Women should ARRANON. These adverse reactions have included altered mental states be advised not to become pregnant when taking ARRANON. (5.3) including severe somnolence, central nervous system effects including ------------------------------ ADVERSE REACTIONS ----------------------- convulsions, and peripheral neuropathy ranging from numbness and The most common (≥ 20%) adverse reactions were: paresthesias to motor weakness and paralysis. There have also been • Adult: anemia, thrombocytopenia, neutropenia, nausea, diarrhea, reports of adverse reactions associated with demyelination, and ascending vomiting, constipation, fatigue,
    [Show full text]
  • BC Cancer Benefit Drug List September 2021
    Page 1 of 65 BC Cancer Benefit Drug List September 2021 DEFINITIONS Class I Reimbursed for active cancer or approved treatment or approved indication only. Reimbursed for approved indications only. Completion of the BC Cancer Compassionate Access Program Application (formerly Undesignated Indication Form) is necessary to Restricted Funding (R) provide the appropriate clinical information for each patient. NOTES 1. BC Cancer will reimburse, to the Communities Oncology Network hospital pharmacy, the actual acquisition cost of a Benefit Drug, up to the maximum price as determined by BC Cancer, based on the current brand and contract price. Please contact the OSCAR Hotline at 1-888-355-0355 if more information is required. 2. Not Otherwise Specified (NOS) code only applicable to Class I drugs where indicated. 3. Intrahepatic use of chemotherapy drugs is not reimbursable unless specified. 4. For queries regarding other indications not specified, please contact the BC Cancer Compassionate Access Program Office at 604.877.6000 x 6277 or [email protected] DOSAGE TUMOUR PROTOCOL DRUG APPROVED INDICATIONS CLASS NOTES FORM SITE CODES Therapy for Metastatic Castration-Sensitive Prostate Cancer using abiraterone tablet Genitourinary UGUMCSPABI* R Abiraterone and Prednisone Palliative Therapy for Metastatic Castration Resistant Prostate Cancer abiraterone tablet Genitourinary UGUPABI R Using Abiraterone and prednisone acitretin capsule Lymphoma reversal of early dysplastic and neoplastic stem changes LYNOS I first-line treatment of epidermal
    [Show full text]
  • Anticancer Alkylating Agents-Part-I.Pdf
    Anticancer Agents Medicinal Chemistry III B Pharm Dr. bilal al-jaidi Assistant Professor, Pharmaceutical Medicinal Chemistry Faculty of Pharmacy, Philadelphia University-Jordan Email: [email protected] Learning Outcome At the end of this lesson students will be able to – Outline the current status, causes and treatment strategies of cancer – Explain the mechanism of action, SAR, therapeutic uses and side effects of following classes of anti-cancer agents: • Alkylating Agents QUIZ = 20 Marks • Heavy metal compounds (Metallating Agents) • Anti-metabolite • Antibiotics • Plant Extracts • Topoisomerase inhibitors • Hormones • Combination of chemotherapy with other treatments • Others First Examination= 20 Marks The Status of Cancer • Cancer is a leading cause of death worldwide, accounting for 12.6 million new cases and 7.6 million deaths every year. THIS IS EQUIVALENT TO ONE PERSON, EVERY 5 SECONDS OF EVERYDAY Source: GLOBOCAN 2008 By 2020 the World Health Organisation (WHO) expects this rise to 16 million. Cancer • A new growth of tissue in which multiplication of cells is uncontrolled and progressive (tumour). • Abnormal cells can spread to other parts of the body (metastasise). Cancer Types Cancer types are categorized based on the functions/locations of the cells from which they originate: Carcinoma: a tumor derived from epithelial cells, those cells that line the inner or outer surfaces of our skin and organs (80-90% of all cancer cases reported) Sarcoma: a tumor derived from muscle, bone, cartilage, fat or connective tissues. Leukemia: a cancer derived from white blood cells or their precursors. Lymphoma: a cancer of bone marrow derived cells that affects the lymphatic system. Myelomas: a cancer involving the white blood cells responsible for the production of antibodies (B lymphocytes).
    [Show full text]
  • Maintenance Therapy in Solid Tumors Marie-Anne Smit, MD, MS,1 and John L
    Review Maintenance therapy in solid tumors Marie-Anne Smit, MD, MS,1 and John L. Marshall, MD2 1 Department of Internal Medicine, 2 Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC The concept of maintenance therapy has been well studied in hematologic malignancies, and now, an increasing number of clinical trials explore the role of maintenance therapy in solid cancers. Both biological and lower-intensity chemotherapeutic agents are currently being evaluated as maintenance therapy. However, despite the increase in research in this area, there has not been consensus about the definition and timing of maintenance therapy. In this review, we will focus on continuation maintenance therapy and switch maintenance therapy in patients with metastatic solid tumors who have achieved stable disease, partial response, or complete response after first-line treatment. aintenance therapy is the subject of an apeutic agents, such as capecitabine and oral 5- increased interest in cancer research. fluorouracil (5-FU), are currently being evaluated as MIn contrast to conventional chemo- maintenance therapy. therapy that aims to kill as many cancer cells as Despite the increase in research in this area, possible, the goal of treatment with maintenance there is no consensus on the definition and timing therapy is to sustain a stable tumor mass, reduce of maintenance therapy. The term maintenance cancer-related symptoms, and prolong the time to therapy is used in a variety of treatment situations, progression and the related symptoms. A thera- such as prolonged first-line therapy and less- peutic strategy that is explicitly designed to main- intense or different therapy given after first-line tain a stable, tolerable tumor volume could in- therapy.
    [Show full text]
  • ARRANON Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION -------------------------------------CONTRAINDICATIONS------------------------ These highlights do not include all the information needed to use None. (4) ARRANON safely and effectively. See full prescribing information for ARRANON. -------------------------WARNINGS AND PRECAUTIONS---------------------- Neurologic Adverse Reactions: Severe neurologic reactions have been ARRANON® (nelarabine) injection, for intravenous use reported. Monitor for signs and symptoms of neurologic toxicity. (5.1) Initial U.S. Approval: 2005 Hematologic Reactions: Complete blood counts including platelets should WARNING: NEUROLOGIC ADVERSE REACTIONS be monitored regularly. (5.2) See full prescribing information for complete boxed warning. Embryo-Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential of the potential risk to the fetus and to use effective Severe neurologic adverse reactions have been reported with the use of contraception; and advise males to use condoms. (5.3, 8.1, 8.3) ARRANON. These adverse reactions have included altered mental states Effects on Ability to Drive and Use Machines: Somnolence may occur. including severe somnolence, central nervous system effects including Advise patients to refrain from these activities until somnolence has convulsions, and peripheral neuropathy ranging from numbness and resolved. (5.6) paresthesias to motor weakness and paralysis. There have also been reports of adverse reactions associated with demyelination, and ascending ------------------------------------ADVERSE REACTIONS------------------------- peripheral neuropathies similar in appearance to Guillain-Barré The most common (≥ 20%) adverse reactions were: syndrome. (5.1) Adult: anemia, thrombocytopenia, neutropenia, nausea, diarrhea, vomiting, constipation, fatigue, pyrexia, cough, and dyspnea. (6.1) Full recovery from these adverse reactions has not always occurred with Pediatric: anemia, neutropenia, thrombocytopenia, and leukopenia. (6.1) cessation of therapy with ARRANON.
    [Show full text]
  • Chlormethine Gel for Treating Mycosis Fungoides-Type Cutaneous T- Cell Lymphoma [ID1589]
    Chlormethine gel for treating mycosis fungoides-type cutaneous T- cell lymphoma [ID1589] Produced by Aberdeen HTA Group Authors Dwayne Boyers1 Elisabet Jacobsen1 Clare Robertson3 Mari Imamura3 Dolapo Ayansina2 Paul Manson3 Gavin Preston4 Miriam Brazzelli3 1 Health Economics Research Unit, University of Aberdeen, UK 2 Medical Statistics Team, University of Aberdeen, UK 3 Health Services Research Unit, University of Aberdeen, UK 4 NHS Grampian, Aberdeen Royal Infirmary, Aberdeen, UK Correspondence to Miriam Brazzelli, Reader (Research) University of Aberdeen, Health Services Research Unit Foresterhill, Aberdeen, AB25 2ZD Email: [email protected] Date completed: 14 April 2020 Version: 2.0 (revised after factual error check) Copyright belongs to University of Aberdeen HTA Group, unless otherwise stated. : Copyright 2020 Queen's Printer and Controller of HMSO. All rights reserved. Source of funding: This report was commissioned by the NIHR Systematic Reviews Programme as project number 130927. Declared competing interests of the authors No competing interests to disclose. Acknowledgements The authors are grateful to Lara Kemp for providing administrative support. Copyright is retained by Recordati Rare Diseases/Helsinn Healthcare SA for Figures 1, 2, 3, 4, 5 and 6, and Table 8. Rider on responsibility for report The view expressed in this report are those of the authors and not necessarily those of the NIHR HTA Programme. Any errors are the responsibility of the authors. This report should be referenced as follows: Boyers D, Jacobsen E, Robertson C, Imamura M, Ayansina D, Manson P, Preston G, Brazzelli M. Chlormethine gel for treating mycosis fungoides-type cutaneous T-cell lymphoma. Aberdeen HTA Group, 2020.
    [Show full text]
  • An Analysis of Toxicity and Response Outcomes from Dose
    Brock et al. BMC Cancer (2021) 21:777 https://doi.org/10.1186/s12885-021-08440-0 RESEARCH ARTICLE Open Access Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer Kristian Brock1* ,VictoriaHomer1, Gurjinder Soul2, Claire Potter1,CodyChiuzan3 and Shing Lee3 Abstract Background: The overwhelming majority of dose-escalation clinical trials use methods that seek a maximum tolerable dose, including rule-based methods like the 3+3, and model-based methods like CRM and EWOC. These methods assume that the incidences of efficacy and toxicity always increase as dose is increased. This assumption is widely accepted with cytotoxic therapies. In recent decades, however, the search for novel cancer treatments has broadened, increasingly focusing on inhibitors and antibodies. The rationale that higher doses are always associated with superior efficacy is less clear for these types of therapies. Methods: We extracted dose-level efficacy and toxicity outcomes from 115 manuscripts reporting dose-finding clinical trials in cancer between 2008 and 2014. We analysed the outcomes from each manuscript using flexible non-linear regression models to investigate the evidence supporting the monotonic efficacy and toxicity assumptions. Results: We found that the monotonic toxicity assumption was well-supported across most treatment classes and disease areas. In contrast, we found very little evidence supporting the monotonic efficacy assumption. Conclusions: Our conclusion is that dose-escalation trials routinely use methods whose assumptions are violated by the outcomes observed. As a consequence, dose-finding trials risk recommending unjustifiably high doses that may be harmful to patients. We recommend that trialists consider experimental designs that allow toxicity and efficacy outcomes to jointly determine the doses given to patients and recommended for further study.
    [Show full text]
  • Chemotherapy: Drugs E-O Policy (Chemo Drug E-O)
    chemo drug e-o 1 Chemotherapy: Drugs E-O Policy Page updated: September 2020 This section contains policy related to billing for injection services, listed in alphabetical order by generic drug name or drug type. For general billing policy information regarding injections services, refer to the Chemotherapy: An Overview section in this manual. Additional policy information for chemotherapy drug services can be found in the Chemotherapy: Drugs A-D Policy and Chemotherapy: Drugs P-Z Policy sections in this manual. Elotuzumab Elotuzumab is a humanized IgG1 monoclonal antibody that specifically targets the SLAMF7 (signaling lymphocytic activation molecule family member 7) protein. SLAMF7 is expressed on myeloma cells independent of cytogenetic abnormalities. SLAMF7 is also expressed on natural killer cells, plasma cells and at lower levels on specific immune cell subsets of differentiated cells within the hematopoietic lineage. Elotuzumab directly activates natural killer cells through both the SLAMF7 pathway and Fc receptors. Elotuzumab also targets SLAMF7 on myeloma cells and facilitates the interaction with natural killer cells to mediate the killing of myeloma cells through antibody-dependent cellular cytotoxicity (ADCC). Indications Elotuzumab is indicated in combination with lenalidomide and dexamethasone for the treatment of patients ages 18 years or older, with multiple myeloma who have received one to three prior therapies. Pre-medicate with dexamethasone, diphenhydramine, ranitidine and acetaminophen. Advise patients that lenalidomide has the potential to cause fetal harm. Authorization An approved Treatment Authorization Request (TAR) is required for reimbursement. The TAR must state that the treatment is for a patient with multiple myeloma who has received one to three prior therapies.
    [Show full text]
  • Rtc-Fertility-Preservation-280318
    Fertility Preservation Oncofertility, social egg freezing and the transgender experience Dr Tamara Hunter FRANZCOG CREI Gynaecologist and Fertility Subspecialist Fertility Preservation • Oncofertility – Chemotherapy – Radiotherapy • Fertility preservation – Female – Male • Transgender fertility preservation • Elective oocyte cryopreservation (social egg freezing Oncofertility • 10% of cancers occur in women under 45yo • 50% have gonadotoxic treatment • 83% survive • Treatment, not disease itself premature ovarian failure – Chemotherapy – Radiotherapy • Loss of fertility • Menopause related complications Gonadotoxicity Risk of gondal dysfunction Sonmezer & Oktay 2004 High risk Medium risk Low risk • Cyclophosphamide • Cisplatin •Vincristine • Ifosfamide • Carboplatin •Methotrexate • Chlormethine • Doxorubicin •Bleomycin • Dactinomycin • Busulfan •Mercaptopurine •Vinblastine • Melphalan • Procarbazine • Chlorambucil Cyclophosphamide will induce permanent amenorrhea in high doses dependent on age 5g at age 40 10g at age 30 20g at age 20 Koyama et al. 1977 Risks of radiotherapy Impact depends on; –field of treatment –dose of radiation –fractionation Risks of radiotherapy • Estimated dose at which half oocytes depleted is 2Gy. • At birth 20 Gy to ovaries will cause ovarian failure • Women <30 15 Gy • Women <40 14 Gy • Women >40 6Gy (Hamish et al. 2005) Risk of radiotherapy In addition; • CNS irradiation may lead to hypogonadotrophic hypogonadism Uterine effects of radiotherapy • Decreased endometrial vascularisation • Decreased endometrial
    [Show full text]
  • 2015 Antiemesis.Pdf
    NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Antiemesis Version 2.2015 NCCN.org Continue Version 2.2015, 09/22/15 © National Comprehensive Cancer Network, Inc. 2015, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. Printed by Alexandre Ferreira on 10/25/2015 6:12:07 AM. For personal use only. Not approved for distribution. Copyright © 2015 National Comprehensive Cancer Network, Inc., All Rights Reserved. NCCN Guidelines Version 2.2015 Panel Members NCCN Guidelines Index Antiemesis Table of Contents Antiemesis Discussion David S. Ettinger, MD/Chair † Steve Kirkegaard, PharmD Σ Eric Roeland, MD The Sidney Kimmel Comprehensive Huntsman Cancer Institute UC San Diego Moores Cancer Cancer Center at Johns Hopkins at the University of Utah Center Michael J. Berger, PharmD/Vice Chair, BCOP Σ Dwight D. Kloth, PharmD, BCOP Σ Hope S. Rugo, MD † ‡ The Ohio State University Comprehensive Fox Chase Cancer Center UCSF Helen Diller Family Cancer Center - James Cancer Hospital Comprehensive Cancer Center and Solove Research Institute Ruth Lagman, MD £ Mayo Clinic Cancer Center Bridget Scullion, PharmD, BCOP Jonathan Aston, PharmD, BCOP, BCPS Σ Dana-Farber/Brigham and Women’s Vanderbilt-Ingram Cancer Center Dean Lim, MD † Cancer Center | Massachusetts City of Hope Comprehensive Cancer Center General Hospital Cancer Center Sally Barbour, PharmD, BCOP, CCP Σ Duke Cancer Institute Cynthia Ma, MD, PhD † John Timoney, PharmD, BCOP † Siteman Cancer Center at Barnes-Jewish Memorial Sloan Kettering Cancer Philip J. Bierman, MD † ‡ Hospital and Washington University School Center Fred & Pamela Buffet Cancer Center of Medicine Barbara Todaro, PharmD Σ Debra Brandt, DO Belinda Mandrell, PhD, RN † Roswell Park Cancer Institute Yale Cancer Center/Smilow Cancer Hospital St.
    [Show full text]