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LEUKERAN 3 (Chlorambucil) 4 Tablets 5
1 PRESCRIBING INFORMATION ® 2 LEUKERAN 3 (chlorambucil) 4 Tablets 5 6 WARNING 7 LEUKERAN (chlorambucil) can severely suppress bone marrow function. Chlorambucil is a 8 carcinogen in humans. Chlorambucil is probably mutagenic and teratogenic in humans. 9 Chlorambucil produces human infertility (see WARNINGS and PRECAUTIONS). 10 DESCRIPTION 11 LEUKERAN (chlorambucil) was first synthesized by Everett et al. It is a bifunctional 12 alkylating agent of the nitrogen mustard type that has been found active against selected human 13 neoplastic diseases. Chlorambucil is known chemically as 4-[bis(2- 14 chlorethyl)amino]benzenebutanoic acid and has the following structural formula: 15 16 17 18 Chlorambucil hydrolyzes in water and has a pKa of 5.8. 19 LEUKERAN (chlorambucil) is available in tablet form for oral administration. Each 20 film-coated tablet contains 2 mg chlorambucil and the inactive ingredients colloidal silicon 21 dioxide, hypromellose, lactose (anhydrous), macrogol/PEG 400, microcrystalline cellulose, red 22 iron oxide, stearic acid, titanium dioxide, and yellow iron oxide. 23 CLINICAL PHARMACOLOGY 24 Chlorambucil is rapidly and completely absorbed from the gastrointestinal tract. After single 25 oral doses of 0.6 to 1.2 mg/kg, peak plasma chlorambucil levels (Cmax) are reached within 1 hour 26 and the terminal elimination half-life (t½) of the parent drug is estimated at 1.5 hours. 27 Chlorambucil undergoes rapid metabolism to phenylacetic acid mustard, the major metabolite, 28 and the combined chlorambucil and phenylacetic acid mustard urinary excretion is extremely 29 low — less than 1% in 24 hours. In a study of 12 patients given single oral doses of 0.2 mg/kg of 30 LEUKERAN, the mean dose (12 mg) adjusted (± SD) plasma chlorambucil Cmax was 31 492 ± 160 ng/mL, the AUC was 883 ± 329 ng●h/mL, t½ was 1.3 ± 0.5 hours, and the tmax was 32 0.83 ± 0.53 hours. -
Chemotherapy in Advanced Ovarian Cancer: an Overview of Randomised Clinical Trials BMJ: First Published As 10.1136/Bmj.303.6807.884 on 12 October 1991
Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials BMJ: first published as 10.1136/bmj.303.6807.884 on 12 October 1991. Downloaded from Advanced Ovarian Cancer Trialists Group Abstract cytotoxic drugs, usually doxorubicin and cyclophos- Objectives-To consider the role of platinum and phamide with or without hexamethylmelamine.45 the relative merits of single agent and combination When, however, doubt was cast on the effectiveness chemotherapy in the treatment of advanced ovarian of doxorubicin by both randomised phase III trials6-8 cancer. and phase II studies in patients not responding to Design-Formal quantitative overview using cisplatin9 several major centres adopted cisplatin plus updated individual patient data from all available cyclophosphamide as standard. Furthermore, when randomised trials (published and unpublished). other trials failed to find significant survival differences Subjects-8139 patients (6408 deaths) included in between single agent cisplatin and cisplatin in combi- 45 different trials. nation with other drugs'0 some centres reverted to Results-No firm conclusions could be reached. using single agent platinum as routine first line treat- Nevertheless, the results suggest that in terms of ment. Recently a large number oftrials have compared survival immediate platinum based treatment was cisplatin with its less nephrotoxic and neurotoxic better than non-platinum regimens (overall relative analogue carboplatin, and although follow up times risk 0-93; 95% confidence interval 0-83 to 1-05); were often short, many institutions have now adopted platinum in combination was better than single agent carboplatin as standard. platinum when used in the same dose (overall Currently it is unclear what constitutes optimal relative risk 0-85; 0*72 to 1-00); and cisplatin and chemotherapy for advanced disease and treatment carboplatin were equally effective (overall relative strategies vary both nationally and internationally. -
Melphalan) for Injection, for Intravenous Use History of Serious Allergic Reaction to Melphalan Initial U.S
HIGHLIGHTS OF PRESCRIBING INFORMATION --------------------DOSAGE FORMS AND STRENGTHS----------------------- These highlights do not include all the information needed to use For Injection: 50 mg per vial, lyophilized powder in a single-dose vial for EVOMELA safely and effectively. See full prescribing information for reconstitution. (3) EVOMELA. ---------------------------CONTRAINDICATIONS---------------------------------- EVOMELA® (melphalan) for injection, for intravenous use History of serious allergic reaction to melphalan Initial U.S. Approval: 1964 WARNING: SEVERE BONE MARROW SUPPRESSION, ---------------------WARNINGS AND PRECAUTIONS-------------------------- HYPERSENSITIVITY, and LEUKEMOGENICITY See full prescribing information for complete boxed warning. • Gastrointestinal toxicity: Nausea, vomiting, diarrhea or oral mucositis may occur; provide supportive care using antiemetic and antidiarrheal • Severe bone marrow suppression with resulting infection or medications as needed. (2.1, 5.2) bleeding may occur. Controlled trials comparing intravenous (IV) • Embryo-fetal toxicity: Can cause fetal harm. Advise of potential risk to melphalan to oral melphalan have shown more myelosuppression fetus and to avoid pregnancy . (5.6, 8.1, 8.3) with the IV formulation. Monitor hematologic laboratory • Infertility: Melphalan may cause ovarian function suppression or testicular parameters. (5.1) suppression. (5.7) • Hypersensitivity reactions, including anaphylaxis, have occurred in approximately 2% of patients who received the IV formulation -
Chapter 1.Pdf
CHAPTER 1 INTRODUCTION AND OUTLINE OF THIS THESIS INTRODUCTION Inflammatory bowel diseases (IBD), comprising Crohn’s disease, ulcerative colitis and IBD- 1 unclassified, are chronic recurrent inflammatory disorders of the (large) intestine with a heterogeneous, but often disabling disease presentation. The prevalence of IBD is increasing worldwide and medical therapies are introduced earlier to improve health-related quality of life and postpone surgical interventions1,2. This has led to the more extensive use of immunosuppressive therapies including biologicals and thiopurines. While the use of tioguanine was soon abandoned due to toxicity concerns3, over the years efficacy data on the use of azathioprine and mercaptopurine for the treatment of IBD has grown4,5. However, due to side effects and ineffectiveness, related to unprofitable metabolism, thiopurine therapy often fails; up to 50% of patients discontinues treatment within 2 years6. Increasing the knowledge on thiopurine metabolism may provide opportunities to further explore the therapeutic usefulness of thiopurines, which both from a patient’s perspective and a pharmacoeconomic perspective is essential. THIOPURINES In the 1950’s Gertrude Elion (1918-1999) worked as an assistant to George Hitchings (1905- 1998), both employees of Burroughs-Wellcome, focussing on the advent of drugs that inhibited cell growth without doing harm to the host cells. They discovered that purine bases are essential components of nucleic acids and vital for cell growth7. Subsequently, they designed the purine antagonists diaminopurine and tioguanine that blocked the synthesis of original nucleic acids and inhibited cell growth8. For the first time a successful treatment of leukaemia became available. Some years later Elion and colleagues also developed mercaptopurine, azathioprine, allopurinol, trimethoprim and acyclovir. -
B. Package Leaflet
B. PACKAGE LEAFLET 1 Package Leaflet: Information for the User Chlorambucil 2 mg tablets chlorambucil Read all of this leaflet carefully before you start taking this medicine because it contains important information for you. - Keep this leaflet. You may need to read it again. - If you have any further questions ask your doctor or nurse. - This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours. - If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4. What is in this leaflet 1. What Chlorambucil is and what it is used for 2. What you need to know before you take Chlorambucil 3. How to take Chlorambucil 4. Possible side effects 5. How to store Chlorambucil 6. Contents of the pack and other information 1. What Chlorambucil is and what it is used for Chlorambucil contains a medicine called chlorambucil. This belongs to a group of medicines called cytotoxics (also called chemotherapy). Chlorambucil is used to treat some types of cancer and certain blood problems. It works by reducing the number of abnormal cells your body makes. Chlorambucil is used for: - Hodgkin's disease and Non-Hodgkin’s Lymphoma. Together, these form a group of diseases called lymphomas. They are cancers formed from cells of the lymphatic system. - Chronic lymphocytic leukaemia. A type of white blood cell cancer where the bone marrow produces a large number of abnormal white cells. -
Safe Handling of Cytotoxic, Monoclonal Antibody & Hazardous Non-Cytotoxic Drugs
PROCEDURE SAFE HANDLING OF CYTOTOXIC, MONOCLONAL ANTIBODY & HAZARDOUS NON-CYTOTOXIC DRUGS TARGET AUDIENCE All nursing, pharmacy and medical staff involved with dispensing, preparation, or administration of medicines. STATE ANY RELATED PETER MAC POLICIES, PROCEDURES OR GUIDELINES Administration and Management of Anti-Cancer Drugs Administration of Cytotoxics in the Home/Community Collection and Disposal of Soiled Linen Dangerous Goods and Hazardous Substances Environmental Management Individual Personal Protective Equipment (Cancer Research Division) Management of Cytotoxic Drug Spill Medication Management Medication Management for Nurses Pharmaceutical Review & Medication Supply Personal Protective Equipment Administration of Intravesical Immunotherapy BCG PURPOSE This procedure provides direction to all hospital staff involved in the management, preparation, transportation, administration of hazardous drugs and related wastes. In particular, safe handling practices for cytotoxic and hazardous non-cytotoxic drugs are outlined. BACKGROUND Hazardous drugs are regulated medicines that have been classified by the National Institute for Occupational Safety and Health (NIOSH) of the United States and/or the Cancer Institute New South Wales as posing a risk to health from occupational exposure. Exposure to hazardous drugs can result in adverse health effects in healthcare workers. The health risk depends on how much exposure a worker has to these drugs and the specific toxicity of the drug. The occupational exposure risk of hazardous drugs is therefore evaluated according to risk of internalisation (by ingestion, absorption through mucous membranes, and penetration of skin) and risk of toxicity (carcinogenicity, genotoxicity, teratogenicity, and reproductive or fertility impairment, organ toxicity) at low doses and continuous exposure. Hazardous drugs include both cytotoxic and non-cytotoxic medicines such as chemotherapy, monoclonal antibodies, immunomodulatory drugs, and some anti-infective drugs. -
Refractory Multiple Myeloma Patients: a Meta-Analysis and Systematic Review
OncoTargets and Therapy Dovepress open access to scientific and medical research Open Access Full Text Article REVIEW Arsenic trioxide-based therapy in relapsed/ refractory multiple myeloma patients: a meta-analysis and systematic review Xuepeng He Abstract: Multiple myeloma (MM) is a clonal malignancy characterized by the proliferation of Kai Yang malignant plasma cells in the bone marrow and the production of monoclonal immunoglobulin. Peng Chen Although some newly approved drugs (thalidomide, lenalidomide, and bortezomib) demonstrate Bing Liu significant benefit for MM patients with improved survival, all MM patients still relapse. Arsenic Yuan Zhang trioxide (ATO) is the most active single agent in acute promyelocytic leukemia, the antitumor Fang Wang activity of which is partly dependent on the production of reactive oxygen species. Due to its multifaceted effects observed on MM cell lines and primary myeloma cells, Phase I/II trials have Zhi Guo been conducted in heavily pretreated patients with relapsed or refractory MM. Therapy regimens Xiaodong Liu varied dramatically as to the dosage of ATO and monotherapy versus combination therapy with Jinxing Lou For personal use only. other agents available for the treatment of MM. Although ATO-based combination treatment Huiren Chen was well tolerated by most patients, most trials found that ATO has limited effects on MM Department of Hematology, patients. However, since small numbers of patients were randomized to different treatment General Hospital of Beijing arms, trials have not been statistically powered to determine the differences in progression-free Military Area of PLA, Beijing, People’s Republic of China survival and overall survival among the experimental arms. -
Efficacy of Ethinylestradiol Re-Challenge for Metastatic Castration-Resistant Prostate Cancer
ANTICANCER RESEARCH 36: 2999-3004 (2016) Efficacy of Ethinylestradiol Re-challenge for Metastatic Castration-resistant Prostate Cancer TAKEHISA ONISHI1, TAKUJI SHIBAHARA1, SATORU MASUI1, YUSUKE SUGINO1, SHINICHIRO HIGASHI1 and TAKESHI SASAKI2 1Department of Urology, Ise Red Cross hospital, Ise, Japan; 2Department of Urology, Mie University Graduate School of Medicine, Tsu, Japan Abstract. Background: There has recently been renewed corticosteroids, estrogens, sipuleucel T and, more recently, interest in the use of estrogens as a treatment strategy for CYP17 inhibitor (abirateron acetate) and androgen castration-resistant prostate cancer (CRPC). The purpose of receptor antagonist (enzaltamide) (2-7). Treatment with this study was to evaluate the feasibility and efficacy of estrogens was used as a palliative therapy for advanced ethinylestradiol re-challenge (re-EE) in the management of prostate cancer, however, the discovery of luteinizing CRPC. Patients and Methods: Patients with metastatic CRPC hormone-releasing hormone (LH-RH) agonists led them to who received re-EE after disease progression on prior EE become less common and they stopped being used in most and other therapy were retrospectively reviewed for prostate- countries in the 1980s (8). One of the reasons for reduction specific antigen (PSA) response, PSA progression-free in their use is the risk of cardiovascular and survival (P-PFS) and adverse events. Results: Thirty-six re- thromboembolic events during therapy. However, several EE treatments were performed for 20 patients. PSA response reports demonstrated the positive oncological results of to the initial EE treatment was observed in 14 (70%) patients. therapy with estrogens, such as diethylstilbestrol (DES) PSA response to re-EE was 33.3% in 36 re-EE treatments. -
Hematologic Oncology Update — Issue 1, 2014
POST-TEST Hematologic Oncology Update — issue 1, 2014 The c o rrec T answer is indicaTed wiTh yellow highlighTin g. 1. Which of the following is true regarding the 6. A Phase II study of single-agent brentux- CRS related to CAR T-cell therapy? imab vedotin for the treatment of relapsed a. It manifests as fever, nausea, myalgia or refractory CD30-positive non-hodgkin and hypotension lymphomas demonstrated promising antitumor b. It is associated with high levels of IL-6 activity in patients with DLBCL with a broad c. It is irreversible range of CD30 expression levels. d. Both a and b a. True b. False 2. Updated results of a pilot trial by Porter and colleagues of chimeric antigen receptor T-cell 7. Results from a Phase II trial comparing therapy for patients with relapsed/refractory consolidation therapy with a single dose of CLL reported an overall response rate of 90y-ibritumomab tiuxetan to rituximab mainte- _____________. nance for patients with newly diagnosed Fl a. 12% who have experienced a response to r-CHOP b. 57% demonstrated statistically significant differ- ences in _____________ favoring rituximab c. 82% maintenance. 3. Tocilizumab, an IL-6 receptor antagonist, is a. Progression-free survival effective at reversing the cytokine release b. Overall survival syndrome associated with chimeric antigen c. Both a and b receptor-modified T-cell therapy. a. True 8. The final stage II results of the Phase b. False III CLL11 trial for patients with CLL and coexisting medical conditions demon- 4. The results of a Phase III study of induction strated that obinutuzumab/chlorambucil was therapy with lenalidomide and dexametha- superior to rituximab/chlorambucil in terms of sone followed by maintenance lenalidomide _____________. -
Essential Thrombocythemia Facts No
Essential Thrombocythemia Facts No. 12 in a series providing the latest information for patients, caregivers and healthcare professionals www.LLS.org • Information Specialist: 800.955.4572 Introduction Highlights Essential thrombocythemia (ET) is one of several l Essential thrombocythemia (ET) is one of a related “myeloproliferative neoplasms” (MPNs), a group of closely group of blood cancers known as “myeloproliferative related blood cancers that share several features, notably the neoplasms” (MPNs) in which cells in the bone “clonal” overproduction of one or more blood cell lines. marrow that produce the blood cells develop and All clonal disorders begin with one or more changes function abnormally. (mutations) to the DNA in a single cell; the altered cells in l ET begins with one or more acquired changes the marrow and the blood are the offspring of that one (mutations) to the DNA of a single blood-forming mutant cell. Other MPNs include polycythemia vera and cell. This results in the overproduction of blood cells, myelofibrosis. especially platelets, in the bone marrow. The effects of ET result from uncontrolled blood cell l About half of individuals with ET have a mutation production, notably of platelets. Because the disease arises of the JAK2 (Janus kinase 2) gene. The role that this from a change to an early blood-forming cell that has the mutation plays in the development of the disease, capacity to form red cells, white cells and platelets, any and the potential implications for new treatments, combination of these three cell lines may be affected – and are being investigated. usually each cell line is affected to some degree. -
VINBLASTINE-VINCRISTINE (Chlvpp-EVA
Chemotherapy Protocol LYMPHOMA CHLORAMBUCIL-DOXORUBICIN-ETOPOSIDE-PREDNISOLONE-PROCARBAZINE- VINBLASTINE-VINCRISTINE (ChlVPP-EVA) Regimen • Lymphoma – ChlVPP-EVA-Chlorambucil-Doxorubicin-Etoposide-Prednisolone- Procarbazine-Vinblastine-Vincristine Indication • Hodgkin’s Lymphoma Toxicity Drug Adverse Effect Chlorambucil Gastro-intestinal disturbance Doxorubicin Cardiomyopathy, alopecia, urinary discolouration (red) Etoposide Hypotension on rapid infusion, hyperbilirubinaemia Weight gain, gastro-intestinal disturbances, hyperglycaemia, Prednisolone CNS disturbances, cushingoid changes, glucose intolerance Procarbazine Insomnia, ataxia, hallucinations, headache Vinblastine Peripheral neuropathy, constipation, jaw pain, ileus Vincristine Peripheral neuropathy, constipation, jaw pain, ileus The adverse effects listed are not exhaustive. Please refer to the relevant Summary of Product Characteristics for full details. Patients diagnosed with Hodgkin’s Lymphoma carry a lifelong risk of transfusion-associated graft versus host disease (TA-GVHD). Where blood products are required these patients must receive only irradiated blood products for life. Local blood transfusion departments must be notified as soon as a diagnosis is made and the patient must be issued with an alert card to carry with them at all times. Monitoring Drugs • FBC, LFTs and U&Es prior to day one and eight of treatment Version 1 (May 2018) Page 1 of 10 Lymphoma- ChlVPP-EVA-Chlorambucil-Doxorubicin-Etoposide-Prednisolone-Procarbazine-Vinblastine-Vincristine Dose Modifications The dose modifications listed are for haematological, liver and renal function and limited drug specific toxicities. Dose adjustments may be necessary for other toxicities as well. In principle all dose reductions due to adverse drug reactions should not be re-escalated in subsequent cycles without consultant approval. It is also a general rule for chemotherapy that if a third dose reduction is necessary treatment should be stopped. -
SUPPLEMENTARY FILE Cellular Fitnessphenotype of Cancer Target
SUPPLEMENTARY FILE Cellular FitnessPhenotype of Cancer Target Genes in Cancer Therapeutics Bijesh George, P. Mukundan Pillai, Aswathy Mary Paul, Revikumar Amjesh, Kim Leitzel, Suhail M. Ali, Oleta Sandiford, Allan Lipton, Pranela Rameshwar, Gabriel N. Hortobagyi, Madhavan Radhakrishna Pillai, and Rakesh Kumar Supplementary Figures Supplementary Figure S1: Fitness-dependency of cellular targets of approved oncology drugs in cancer cell lines. A, Distribution of alterations in the cellular fitness in esophageal cancer cell lines upon selective knockdown of FSPS test gene. The values are plotted as boxplots with positive and negative changes in the cellular fitness for each cell line, represented by a single dot. B, Effect of knocking down of indicated targets in Head and Neck carcinoma cell lines. C, Distribution of 47 cancer targets of FDA-approved drugs, including, a subset of its 15 priority therapeutic targets in across cancer- types for which drugs targeting these cellular targets are approved. D, Distribution of 47 fitness targets across 19 cancer types for which drugs targeting these molecules are approved corresponds to the loss of Fitness score for were taken from Cancer Dependency Map (23). Supplementary Figure S2: Cellular targets of approved oncology drugs as excellent fitness genes in cancer-types for which drugs targeting these are not approved. Distribution of 43 cellular fitness genes with a significant loss of cellular fitness upon their depletion across peripheral nervous system, large intestine and ovarian cell lines