The easy book of cancer pharmacology 9781634850438, 1634850432
185 65 4MB
English Pages [526] Year 2016
THE EASY BOOK OF CANCER PHARMACOLOGY
THE EASY BOOK OF CANCER PHARMACOLOGY
Library of Congress Cataloging-in-Publication Data
CONTENTS
FOREWORD
PREFACE
Chapter 1: ABIRATERONE: ABIRATERONE ACETATE:
CB7630: ZYTIGA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics [2]
Mechanism of Resistance
Indications [2]
Dosages
Methods of Preparation/Administration
Special Information and Cautions [2]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Immunisations
Warnings [2]
Mineralocorticoid Excess
Adrenocortical Insufficiency
Hepatotoxicity
Food Effect
Toxicities [2]
Dose Modifications [2]
Interactions [2]
CONCLUSION
REFERENCES
Chapter 2: ALBUMIN-BOUND (NAB) PACLITAXEL, ABRAXANE®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
MECHANISM OF ACTION
Pharmacokinetics
INDICATIONS
Metastatic Breast Cancer
Metastatic Pancreatic Adenocarcinoma
Dosages
METHODS OF PREPARATION/ADMINISTRATION
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly
Pediatric
Renal
Hepatic
Immunisations
Pregnancy
Breast-Feeding
TOXICITIES [9, 10]
Dose Modifications
INTERACTIONS
CONCLUSION
REFERENCES
Chapter 3:
AFLIBERCEPT. ZALTRAP®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
MECHANISM OF ACTION
MECHANISM OF RESISTANCE
PHARMACOKINETICS [6]
INDICATIONS
DOSAGES
METHODS OF PREPARATION/ADMINISTRATION [6]
SPECIAL INFORMATION AND CAUTIONS [6]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
WARNINGS [6]
Hemorrhage
Gastrointestinal Perforation
Compromised Wound Healing
Fistula Formation
Hypertension
Arterial Thromboembolic Events
Proteinuria
Neutropenic Complications
Diarrhea and Dehydration
Pregnancy and Nursing
Immunisations
TOXICITIES
DOSE MODIFICATIONS
INTERACTIONS
CONCLUSION
REFERENCES
Chapter 4:
AXITINIB. INLYTA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics [2, 3]
Mechanism of Resistance [3]
Indications
Dosage
Methods of Preparation/Administration [1]
Special Information and Cautions [1]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Breast-Feeding
Pregnancy
Immunisations
Warnings [1]
Hypertension
Thromboembolic Events
Hemorrhagic Events
Toxicities [1]
Dose Modifications [1]
Hepatic Impairment
Concomitant Strong CYP3A4/5 Inhibitors
Concomitant Strong CYP3A4/5 Inducers
Interactions [1]
CYP3A4/5 Inhibitors
CYP1A2 and CYP2C19 Inhibitors
CYP3A4/5 Inducers
CONCLUSION
REFERENCES
Chapter 5: BEVACIZUMAB. AVASTIN®
ABSTRACT
INTRODUCTION
DRUG CLASSIFICATION
MECHANISM OF ACTION
PHARMACOKINETICS
MECHANISM OF RESISTANCE
INDICATIONS [10]
DOSAGES [10]
METHODS OF ADMINISTRATION/PREPARATION [10]
SPECIAL INFORMATION AND CAUTIONS [10]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Immunisations
Lactation
Patients of Reproductive Potential
WARNINGS [10]
Gastrointestinal (GI) Perforations and Fistulae
Non-Gastrointestinal Fistulae
Surgery and Wound Healing Complications
Arterial Thromboembolic Events
Venous Thromboembolic Events
Haemorrhage
Hypertension
Posterior Reversible Encephalopathy Syndrome (PRES)
Proteinuria
Infusion Reactions
Embryo-fetal Toxicity
Ovarian Failure
TOXICITIES [10]
DOSE MODIFICATIONS [10]
INTERACTIONS [10]
CONCLUSION
REFERENCES
Chapter 6:
BLEOMYCIN. BLEO-KYOWA. BLENOXANE
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics
Mechanism of Resistance
INDICATIONS
DOSAGES
Intravenous/Intramuscular
Germ Cell Tumours
Intravenous
Hodgkin’s Lymphoma
Intra-Pleural
Sclerosing Agent for Chemical Pleurodesis
METHODS OF PREPARATION/ADMINISTRATION
Intravenous/Intra-Arterial
Intramuscular
Intrapleural
Subcutaneous
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy and Breast-Feeding
WARNINGS
Pulmonary Toxicity
Idiosyncratic Reactions
Renal and Hepatic Toxicity
TOXICITIES
DOSE MODIFICATIONS
INTERACTIONS
CONCLUSION
REFERENCES
Chapter 7:
CABAZITAXEL. JEVTANA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification [1, 2]
Mechanism of Action [1-4]
Pharmacokinetics [1, 3]
Mechanism of Resistance [2]
Indications [1, 3, 4]
Dosages [1, 3, 4]
METHODS OF PREPARATION/ADMINISTRATION [1, 3, 4]
Step 1 (1st Dilution)
Step 2 (2nd Dilution)
Stability
Premedication
Administration
Special Information and Cautions [1, 3, 4]
Contraindications
Elderly
Pediatric
Renal
Hepatic
Immunisations
Pregnancy
Breast-Feeding
Warnings [1, 3, 4]
Renal Failure
Hypersensitivity
Diarrhoea
Neutropenia
Toxicities [1, 3, 4]
Dose Modifications [1, 3, 4]
Interactions [1, 3, 4]
CONCLUSION
REFERENCES
Chapter 8:
CABOZANTINIB (XL184). COMETRIQ®
ABSTRACT
INTRODUCTION
DRUG CLASSIFICATION
MECHANISM OF ACTION
PHARMACOKINETICS [17, 18]
MECHANISM OF RESISTANCE
INDICATIONS
DOSAGES
METHODS OF PREPARATION/ADMINISTRATION
SPECIAL INFORMATION AND CAUTIONS [17, 18]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Pregnancy and Breast Feeding
Immunizations
WARNINGS [17, 18]
Haemorrhage
Hypertension
Osteonecrosis
Palmar-Plantar Erythrodysaesthesia Syndrome (PPES)
Perforations, Fistulas, and Intra-Abdominal Abscesses
Prolongation of QT Interval
Proteinuria
Proton Pump Inhibitors
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Thromboembolic Events
Wound Complications
TOXICITIES [17, 18]
DOSE MODIFICATIONS [ACCORDING TO COMMON TERMINOLOGY CRITERIA FOR ADVERSE EVENTS (CTCAE)] [17, 18]
Hematologic Toxicities
Other Non-Hematologic Toxicities
Permanent Discontinuation
INTERACTIONS [4, 17, 18]
Strong CYP3A4 Inducers
Strong CYP3A4 Inhibitors
Bisphosphonates
CONCLUSION
REFERENCES
Chapter 9:
CAPECITABINA. XELODA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
PHARMACOKINETICS
Mechanism of Resistance
Indications
METHODS OF PREPARATION/ADMINISTRATION
Dosage
SPECIAL INFORMATION AND CAUTIONS [5]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Liver Impairment
Immunisations
Pregnancy
Lactation
Warnings
DPD Deficiency
Toxicities [6]
Dose Modification [5]
Grade 1 Toxicities
Grade 2
Grade 3
Grade 4
Note
Interactions [6]
CONCLUSION
REFERENCES
Chapter 10: CARBOPLATIN. PARAPLATIN®. CBDCA. DIAMMINEPLATINUM (II). CIS-(1,1.CYCLOBUTANEDICARBOXYLATO). CIS-DIAMMINE(1,1-CYCLOBUTANEDIOCARBOXYLATO) PLATINUM
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
PHARMACOKINETICS [4, 5]
Mechanism of Resistance
Indications [4]
Dosages
Maximum AUC-Based Carboplatin Dose
METHODS OF PREPARATION/ADMINISTRATION [4]
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunizations
Pregnancy
Breast-Feeding
WARNINGS
Emesis
Bone Marrow Suppression
Nephrotoxicity
Neurotoxicity
Visual Disorders
Ototoxicity
Allergic Reactions
Liver Toxicity
TOXICITIES [4, 5]
DOSE MODIFICATIONS [4]
Interactions [5]
CONCLUSION
REFERENCES
Chapter 11: CETUXIMAB. ERBITUX®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification [3]
Mechanism of Action [3]
Pharmacokinetics [3]
Mechanism of Resistance
Indications [3]
Dosages [3]
1. Squamous Cell Carcinoma of the Head and Neck
1.1. Erbitux in Combination with Radiation Therapy or in Combination with Platinum-Based 48 Therapy with 5-FU
1.2. Erbitux Monotherapy
2. Colorectal Cancer
Methods of Preparation/Administration [3]
Special Cautions [3]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Warnings [3]
Infusion Reactions
Hypomagnesemia and Electrolyte Abnormalities
Dermatology Toxicity
Cardiopulmonary Arrest
Pulmonary Toxicity
Toxicity [3]
Dose Modifications [3]
1. Infusion Reactions
2. Dermatological Toxicity
Interactions [3]
CONCLUSION
REFERENCES
Chapter 12: CISPLATIN, PLATINOL®, PLATINOL®-AQ
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
PHARMACOKINETICS [3]
MECHANISMS OF RESISTANCE [5, 6]
INDICATIONS [7, 8]
Dosages
METHODS OF PREPARATION/ADMINISTRATION [2]
SPECIAL INFORMATION AND CAUTIONS [2]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment [14, 15]
Hepatic Impairment
Immunizations
TOXICITIES [2, 16]
DOSE MODIFICATIONS
If Toxicities Related to Grades: [2, 16]
INTERACTIONS [3]
CONCLUSION
REFERENCES
Chapter 13:
CRIZOTINIB. XALKORI®
ABSTRACT
INTRODUCTION
DRUG CLASSIFICATION
MECHANISM OF ACTION
PHARMACOKINETICS [1, 4, 5]
MECHANISM OF RESISTANCE
INDICATIONS
DOSAGE
METHODS OF PREPARATION/ADMINISTRATION
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly Patients
Paediatric Patients
Renal Impairment
Hepatic Impairment
Immunisations
Radiation
WARNINGS
Hepatic Laboratory Abnormalities
QT Interval Prolongation
Bradycardia
Pneumonitis
ALK Testing
Pregnancy, Breast-Feeding, Fertility
Vision Disorders
TOXICITIES [1, 9]
DOSE MODIFICATIONS [1]
INTERACTIONS [5]
CONCLUSION
REFERENCES
Chapter 14: CYTARABINE: ARA-C: CYTOSAR U: CYTOSINE ARABINOSIDE: TARABINE PFS,
ARABINOSYLCYTOSINE, 1-Β-ARABINOSYLCYTOSINE
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics [4, 5, 6]
Indications [1-4]
Dosages [1, 3, 6]
Methods of Preparation/Administration [1-4]
Special Information and Cautions
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Myelosuppression
Cytarabine Syndrome
Toxicities [1, 6]
Adverse Effect Due to High-Dose Cytarabine [1]
Dose Modifications
Renal Impairment in High-Dose Cytarabine [3]
Hepatic Impairment in High-Dose Cytarabine [3]
Low-Dose Cytarabine [5]
Interactions [1, 3, 6]
CONCLUSION
REFERENCES
Chapter 15:
DENOSUMAB, PROLIA®, XGEVA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics
Mechanism of Resistance
Indications [3, 4, 5]
Dosage [2]
Methods of Preparation/Administration [2]
Special Information and Cautions
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Pregnancy
Warnings [2]
Bone Fractures
Dermatologic Reactions
Hypersensitivity
Hypocalcemia
Infection
Osteonecrosis of the Jaw (ONJ)
Musculoskeletal Pain
Dose Modifications [2]
Toxicities [2]
Interactions [2]
CONCLUSION
REFERENCES
Chapter 16: DOCETAXEL.TAXOTERE®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification [3-5]
Mechanism of Action [3-4]
Mechanism of Resistance
Pharmacokinetics [3, 4]
Indications [3, 4]
Breast Cancer
NSCLC
Hormone Refractory Prostate Cancer
Gastric Adenocarcinoma
Squamous Cell Carcinoma of the Head and Neck Cancer
Dosages [3-5]
Metastastic Breast Cancer
Adjuvant Breast Cancer
NSCLC
Prostate Cancer Hormonorefractory
Gastric Cancer
Head and Neck Tumours
For All Patients
Methods of Preparation/Administration [3-5]
Dilution for Infusion
Administration
Stability
Special Information and Cautions [3-5]
Contraindications
Concentrate Vial
Solvent Vial
Elderly
Pediatric
Renal
Hepatic
Immunisations
Pregnancy
Breast-Feeding
Warnings [3, 5]
Hypersensitivity Reactions
Severe Fluid Retention
Toxicities [4]
Dose Modifications [4, 5]
Interactions [3-5]
CONCLUSION
REFERENCES
Chapter 17:
DOXORUBICIN HYDROCHLORIDE. ADRIAMYCIN
ABSTRACT
INTRODUCTION [1, 2]
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action [2]
Pharmacokinetics [3]
INDICATIONS [4]
PREPARATIONS AND ADMINISTRATION [4, 5]
DOSAGES [4, 5]
Doxorubicin
Caelyx
Breast Cancer/Ovarian Cancer
Multiple Myeloma
AIDS-Related Kaposi’s Sarcoma
Myocet
Metastatic Breast Cancer (First Line Treatment)
For All Patients
SPECIAL INFORMATION AND CAUTIONS [4, 5, 6]
Renal Impairment
Hepatic Impairment
Pediatric Patients
Elderly
Pregnancy
Women of Child-Bearing Potential
Breast-Feeding
Fertility
TOXICITIES [5, 6]
DOSE MODIFICATIONS [4, 5]
STOMATITIS
HAEMATOLOGICAL TOXICITY
Impaired Cardiac Function
Impaired Hepatic Function
Impaired Renal Function
INTERACTIONS [7]
CONCLUSION
REFERENCES
Chapter 18:
ENZALUTAMIDE. XTANDI®. MVD3100
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action [1]
Pharmacokinetics
Mechanism of Resistance
Indications [7, 8]
Dosages [3]
Methods of Preparation/Administration [4]
Special Information and Cautions [1, 3]
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Seizures
Hypertension
Prolonged QTc
Toxicities [10]
DOSE
MODIFICATIONS
INTERACTIONS [4]
CONCLUSION
REFERENCES
Chapter 19:
ERLOTINIB, TARCEVA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics
Mechanism of Resistance
Indications
Dosages
Methods of Preparation/Administration
Special Information and Cautions [11]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Myocardial Infarction (MI)/Ischemia
Interstitial Lung Disease (ILD)
Gastrointestinal Perforations
Renal Impairment
Hepatotoxicity
Bullous and Exfoliative Skin Disorders
Ocular Disorders
Cerebrovascular Accident (CVA)
Microangiopathic Hemolytic Anemia (MAHA)
Hemorrhage in Patients Taking Warfarin
Note
Toxicities [11]
Dose
Modifications
CONCLUSION
REFERENCES
Chapter 20:
ETOPOSIDE: VP16: VEPESID: ETOPOPHOS
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification [1]
Mechanism of Action [1, 3]
Pharmacokinetics [4]
Indications [3, 5]
Dosages [5]
Methods of Administration/Preparation [5]
Special Information and Cautions [3, 5]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Myelosuppression
Anaphylaxis
Hypotension
Skin Reactions
Mutagenicity and Carcinogenicity
Liver and Renal Impairment
Fertility
Toxicities [5]
Dose Modifications [3, 5]
Etoposide Cycles Should Not Begin If:
Doses Following the First Dose Should Be Adjusted if:
Patients with Impaired Renal Function:
Patients with Impaired Hepatic Function:
Interactions [6]
Major Interactions:
Milder Interactions:
CONCLUSION
REFERENCES
Chapter 21:
EVEROLIMUS. AFINITOR®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification [4, 5]
Mechanism of Action [4, 5]
Indications [4, 5]
Breast Cancer
Renal Cancer
Pancreatic Neuroendocrine Tumours (PNET)
Renal Angiomyolipoma
Mechanism of Preparation/Administration [4, 5]
Dosage [4, 5]
Pharmacokinetics [4, 5]
Special Information and Cautions [4, 5]
Contraindications
Immunisations
Pregnancy
Breast-Feeding
Warnings [4, 5]
Infections
Renal Failure
Mouth Ulcers
Non-Infectious Pneumonitis
Laboratory Alterations
Toxicity [4, 5]
Dose Modifications [4, 5]
Interactions [4, 5]
CONCLUSION
REFERENCES
Chapter 22: GEFITINIB
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics
Mechanism of Resistance
Indications
Dosages
Methods of Preparation/Administration
Special Information and Cautions [9, 10]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Ocular Disorders
Skin Disorders
Gastrointestinal Perforation
Diarrhoea
Interstitial Lung Disease (ILD)
Hepatotoxicity
Toxicities [11]
Dose Modifications [11, 12]
Interactions
CONCLUSION
REFERENCES
Chapter 23: GEMCITABINE. GEMZAR®
ABSTRACT
INTRODUCTION
DRUG CLASSIFICATION
MECHANISM OF ACTION
PHARMACOKINETICS
INDICATIONS [3-9]
DOSAGE
METHODS OF PREPARATION/ADMINISTRATION
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Toxicities
DOSE MODIFICATION
INTERACTIONS
Radiotherapy
Live Vaccines
CONCLUSION
REFERENCES
Chapter 24: IMATINIB. GLEEVEC®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action [3]
Pharmacokinetics [3-5]
MECHANISM OF RESISTANCE [6]
INDICATIONS [3-6]
Chronic Myeloid Leukemia
Myelodysplastic/Myeloproliferative Diseases (MDS/MPD)
Hypereosinophilic Syndrome (HES) and/or Chronic Eosinophilic Leukemia(CEL)
Kit+ Gastrointestinal Stromal Tumors (GIST)
Dermatofibrosarcoma Protuberans (DFSP)
DOSAGES [3-6]
METHODS OF ADMINISTRATION/PREPARATION [3-6]
SPECIAL INFORMATION AND CAUTIONS [3-6]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast Feeding
WARNINGS
Cytopenias
Bullous Dermatologic Reactions
Hypothyroidism
Gastrointestinal Perforation
Edema and Severe Fluid Retention
Cardiogenic Shock/Left Ventricular Dysfunction
Haemorrhage
Severe Congestive Heart Failure and Left Ventricular Dysfunction
TOXICITIES [3-6]
DOSE MODIFICATIONS [3-6]
Dose Modifications in Hepatic Impairment
INTERACTIONS [3-7]
CONCLUSION
REFERENCES
Chapter 25: IPILIMUMAB
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY [6]
Drug Type
Mechanism of Action
Pharmacokinetics
Indications
Dosage
Methods of Preparation/Administration
Special Informations and Cautions [6]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Immune-Mediated Adverse Reactions
Toxicity [6]
Interactions
Steroids
Anticoagulants
CONCLUSION
REFERENCES
Chapter 26: IRINOTECAN.CPT-11. CAMPTOSAR®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification [4, 5]
Pharmacokinetics [4, 5]
Mechanisn of Resistance [1-3]
Indications [4, 5]
Dosages [4, 5]
Single Agent
Combination
METHODS OF PREPARATION/ADMINISTRATION
Special Information and Cautions [4, 5]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Immunisations
Warnings [4, 5]
Diarrhoea (Early and Late)
Myelosuppression
Pregnancy
Breastfeeding
Gilbert Syndrome
Extravasation
INTERACTIONS [4, 5]
CYP3A4 Enzyme-Inducers
Anticonvulsants
Antibiotics
St. John’s Wort
5-FU/Leucovorin (LV)
Dexamethasone
Ketoconazole
Toxicities [4, 5]
CONCLUSION
REFERENCES
Chapter 27: LAPATINIB
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
MECHANISM OF ACTION
PHARMACOKINETICS
MECHANISM OF RESISTANCE
Indications
Dosages
METHODS OF PREPARATION/ADMINISTRATION
Note
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
WARNINGS
Left Ventricular Ejection Fraction (LVEF
Hepatotoxicity
QT Interval Prolongation
Diarrhoea
Interstitial Lung Disease and Pneumonitis
Rash
TOXICITIES
DOSE MODIFICATION
Cardiac Events
Hepatic Impairment
Interactions
CONCLUSION
REFERENCES
Chapter 28:
LENVATINIB, LENVIMA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics
Mechanism of Resistance
Indications
Dosages
Methods of Administration/Preparation
Special Information and Cautions
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Thyroid Hormones
Blood Pressure
Cardiac Impairment
Toxicity [2, 5]
Dose Modifications
Hypertension
Proteinuria
Interactions
CONCLUSION
REFERENCES
Chapter 29:
MITOMYCIN C
MITOMYCIN-C KYOWA [3], MUTAMYCIN, AMETYCINE,
MITOCIN-C, MITOLEM,
MITO-MEDAC [1] MITOSOL [12]
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Pharmacokinetics
MECHANISM OF RESISTANCE [18]
INDICATIONS
DOSAGES
METHODS OF PREPARATION/ADMINISTRATION
IV
Intravesical
Intraocular
Intraperitoneal
Intra-Arterial
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
WARNINGS
Extravasation
Skin Contact
Use of Creams
With Radiotherapy and Other Antineoplastic Agents
Intraarterial Injection
Use of Oxygen
INTERACTIONS
TOXICITIES [3, 19]
DOSE MODIFICATIONS
Dosage in Renal Impairment [26]
Dosage in Hepatic Impairment [27]
CONCLUSION
REFERENCES
Chapter 30:
NINDETANIB. VARGATEF®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification [1, 2]
Mechanism of Action [1, 2]
Pharmacokinetics [3]
MECHANISM OF RESISTANCE
Limited Data
Indications [1, 3]
Dosages [3]
METHODS OF ADMINISTRATION/PREPARATION [3]
Special Information and Cautions [3]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings [3]
Liver Tests
Gastrointestinal Symptoms
Arterial Thromboembolic Events
Bleeding and Gastrointestinal Perforation
Dose Modifications [3]
Diarrhoea, Nausea, and/or Vomiting
Toxicity [3]
Interactions [3]
CONCLUSION
REFERENCES
Chapter 31:
NIVOLUMAB. OPDIVO®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Type
Mechanism of Action [5-7]
Pharmacokinetics [5-7]
Indications [5-7]
Dosage [5-7]
Methods of Preparation/Administration [5-7]
Special Informations and Cautions [5-7]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings [5-7]
Immune-mediated adverse reactions
Pneumonitis
Colitis
Hypothyroidism and hyperthyroidism
TOXICITY [6, 7]
DOSE MODIFICATIONS [6-7]
INTERACTIONS [6-7]
CONCLUSION
REFERENCES
Chapter 32:
OXALIPLATIN. 1-OHP, L-OHP, OXALATOPLATIN,
OXALIPLATINUM, ELOXATIN
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action [2]
Pharmacokinetics [3]
Mechanism of Resistance [2]
Indications
Dosages
Methods of Preparation/Administration [3]
Special Information and Cautions
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunizations
Warnings
Pulmonary Toxicity
Allergic Reactions
Neuropathy
Hepatotoxicity
Pregnancy
Extravasation [11, 12]
Toxicities [2, 3, 13]
Note
Dose Modifications [3, 4]
Interactions [3]
CONCLUSION
REFERENCES
Chapter 33: PACLITAXEL: TAXOL
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics [4]
Indications [4]
Ovarian Cancer
Breast Cancer
NSCLC
AIDS-Related Kaposi’s Sarcoma (2nd Line Therapy)
Off-Label Indications
Dosages [4, 5]
Ovarian Cancer
Breast Cancer
AIDS-Related Kaposi’s Sarcoma (2nd Line Therapy)
Methods of Preparation/Administration [4, 5]
Special Information and Cautions [4, 5]
Contraindications
Excipients
Elderly [6]
Pediatric
Renal
Hepatic
Immunisations
Pregnancy
Breast-Feeding
Warnings [4]
Hypersensitivity
Neutrophils
Toxicities [4]
Dose Modifications [4, 5]
Hepatic Impairment
Neutropenia
Interactions [4]
CONCLUSION
REFERENCES
Chapter 34:
PANITUMUMAB. VECTIBIX®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics
Mechanism of Resistance
Indications
Dosages
Methods of Preparation/Administration
Special Information and Cautions
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Lactation
Warnings
Infusion Reactions
Electrolyte Depletion/Monitoring
Photosensitivity
Dermatology Toxicity
Toxicities
Dose Modifications
1. For Infusion Reactions
2. Dermatologic Toxicity
3. Ocular or Pulmonary Toxicity
Interactions
CONCLUSION
REFERENCES
Chapter 35:
PAZOPANIB. VOTRIENT®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics [1]
INDICATIONS [1]
DOSAGE [1]
METHODS OF ADMINISTRATION/PREPARATION [1]
SPECIAL INFORMATION AND CAUTIONS [1]
Contraindications
Elderly Patient
Pediatric Patients
Renal Impairment
Hepatic Impairment
Fertility
Pregnancy (Category D)
Breast-Feeding
WARNINGS [1]
TOXICITIES [1]
DOSE MODIFICATIONS [1]
Other Dose Modifications
INTERACTIONS [1]
Combination with Other Systemic Anti-Cancer Therapies
Effect of Pazopanib on Other Drugs
CONCLUSION
REFERENCES
Chapter 36:
PEMBROLIZUMAB. KEYTRUDA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY [5-7]
Drug Type
Mechanism of Action
Indications
Melanoma
Pharmacokinetics
Non-Small Cell Lung Cancer (NSCLC)
Gastric and Gastroesophageal Junction Adenocarcinomas
Dosage
Methods of Preparation/Administration
Administration
SPECIAL INFORMATIONS AND CAUTIONS [5-7]
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Immune-Mediated Adverse Reactions
Toxicity [7]
Dose Modifications [5-7]
Note
Interactions [5-7]
CONCLUSION
REFERENCES
Chapter 37: PEMETREXED. ALIMTA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Pharmacokinetics
Mechanisn of Resistance [1]
Indications [1]
Dosages
Methods of Preparation/Administration [2, 3]
Special Information and Cautions
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Warnings
Contraception
Third Space
Concomitant Use of Non-Steroidal Anti-Inflammatories (NSAIDs)
NSAIDs with Short Half-Lives
NSAIDs with Long Half-Lives
Premedications
Interactions
1. NSAIDs [2]
2. Vaccines
3. Nephrotoxic DRUGS
4.
Concurrent Administration of Tubularly Secreted Substances
Toxicities [2, 3]
Dose Modification
CONCLUSION
REFERENCES
Chapter 38:
PERTUZUMAB. PERJETA
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
PHARMACOKINETICS [5, 6]
Mechanism of Resistance
Indications
Dosages
METHODS OF PREPARATION/ADMINISTRATION
SPECIAL INFORMATION AND CAUTIONS
Contraindications [6]
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Immunisations
WARNINGS
Left Ventricular Dysfunction
Embryo-Fetal Toxicity
Pregnancy
Lactation
Infusion Related Adverse Effects
TOXICITIES
DOSE MODIFICATIONS
1. Left ventricular dysfunction
2. Hypersensitivity reactions
INTERACTIONS
CONCLUSION
REFERENCES
Chapter 39:
REGORAFENIB. STIVARGA®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics
Mechanism of Resistance
Indications
Dosages [6]
Methods of Administration [6]
SPECIAL INFORMATION AND CAUTIONS [6]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
WARNINGS [6]
Hepatotoxicity
Hemorrhage
Hand-Foot Skin Reaction (HFSR)
Hypertension
Reversible Posterior Leukoencephalopathy Syndrome (RPLS)
Gastrointestinal Perforation or Fistula
Wound Healing Complications
Embryo-Fetal Toxicity
Breastfeeding
IMMUNISATIONS
TOXICITIES [6]
DOSE MODIFICATIONS [6]
INTERACTIONS
CONCLUSION
REFERENCES
Chapter 40:
SORAFENIB, NEXAVAR®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action [3-5]
Mechanism of Resistance [3-5]
Pharmacokinetics [3-5]
Indications [3-5]
Dosages [3-5]
Methods of Administration/Preparation [3-5]
Special Information and Cautions [3-5]
Elderly
Pediatric
Renal impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings [3-5]
Gastrointestinal Perforation
Hypertension
Dermatologic Toxicities
QT Prolongation
Cardiac Ischemia
Bleeding
Drug-Induced Hepatitis
Impairment of Thyroid Stimulating Hormone (TSH)
Wound Healing
Toxicity [3-5]
Dose Modifications [3-5]
Interactions [3-5]
Cyp3a4 Inducers
Examples
Exceptions
Warfarin
CONCLUSION
REFERENCES
Chapter 41: STREPTOZOCIN. ZANOSAR®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics [1]
Mechanism of Resistance
Indications
Advanced Neuroendocrine Carcinoma
Pancreatic Adenocarcinoma
Advanced Adrenal Carcinoma
Dosage
Methods of Preparation/Administration
Special Information and Cautions
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Hypoglycaemia
Radiotherapy
Proteinuria
Note
Toxicities [1]
Dose Modifications [1]
Interactions [1]
CONCLUSION
REFERENCES
Chapter 42:
SUNITINIB. SUTENT®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics
Mechanism of Resistance
Indications
Dosages
Method of Preparation/Administration
Special Information and Cautions
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Pregnancy, Fertility and Breastfeeding
Immunisations
Warnings
Toxicities [17]
Dose Modifications
Drug Interactions
CYP3A4 Inhibitors
CYP3A4 Inducers
CONCLUSION
REFERENCES
Chapter 43:
TRASTUZUMAB EMTANSINE (TDM-1)
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
MECHANISM OF ACTION
PHARMACOKINETICS [8, 9]
MECHANISM OF RESISTANCE
INDICATIONS
DOSAGES
METHODS OF PREPARATION/ADMINISTRATION
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
DOSE MODIFICATIONS
TOXICITIES [8]
Hepatotoxicity
Infusion or Hypersensitivity Reactions
Left Ventricular Ejection Dysfunction
Thrombocytopenia
Pulmonary Toxicity
Peripheral Neuropathy
INTERACTIONS
CONCLUSION
REFERENCES
Chapter 44: TEMOZOLOMIDE. TEMODAL®. TEMODAR®.SCHS2.365. NSC 362856
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action [1]
Pharmacokinetics [1, 2]
Mechanism of Resistance [1]
Indications
Dosage [2, 4]
Concomitant with RT
Adjuvant Setting
Advanced Setting
Methods of Preparation/Administration [1, 2]
Special Information and Cautions
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breast-Feeding
Warnings
Myelosuppression
Second Neoplasias
Dose Modifications [3, 5]
Interactions
CONCLUSION
REFERENCES
Chapter 45: TEMSIROLIMUS. CCI-779. TORISEL®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetics [6]
Mechanism of Resistance
Indications [6, 9]
Dosages [10]
RCC
Mantle Cell Lymphoma
Methods of Preparation/Administration [6]
Special Information and Cautions [10]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Immunisations
Breastfeeding
Childbearing
Overdose
Warnings [10]
Hypersensitivity/Infusion Reactions
Hyperglycemia and Hyperlipemia
Interstitial Lung Disease (ILD)
Bowel Perforation
Abnormal Would Healing
Renal Failure
Toxicities [9]
Dose Modifications [9, 10]
1. Haematological Toxicity
2. Hepatic Impairment
3. Renal Impairment
Drug Interactions [10]
1. Agents Inducing Cytochrome P4503A (CYP3A) Metabolism
2. Agents Inhibiting CYP3A Metabolism
3. Sunitinib
CONCLUSION
REFERENCES
Chapter 46:
TOPOTECAN, HYCAMTIN®
ABSTRACT
CLINICAL PHARMACOLOGY
Drug Classification
MECHANISM OF ACTION
PHARMACOKINETICS [7]
MECHANISM OF RESISTANCE
INDICATIONS [6]
DOSAGE [7]
METHODS OF PREPARATION/ADMINISTRATION [7]
SPECIAL INFORMATION AND CAUTIONS [7]
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
WARNINGS [7]
Bone Marrow Suppression
Diarrhoea
Interstitial Lung Disease
Pregnancy and Breast-Feeding
Extravasation
Overdoses
TOXICITIES [7]
DOSE MODIFICATIONS
DRUG INTERACTIONS [7]
CONCLUSION
REFERENCES
Chapter 47: TRASTUZUMAB. HERCEPTIN®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
MECHANISM OF ACTION
PHARMACOKINETICS [6]
MECHANISM OF RESISTANCE
METHODS OF PREPARATION/ADMINISTRATION
Breast Cancer [6, 18]
Metastatic Gastric Cancer [6, 18]
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
WARNINGS
TOXICITIES [6, 18]
DOSE MODIFICATIONS
INTERACTIONS
CONCLUSION
REFERENCES
Chapter 48: VANDETANIB (ZD 6474). CAPRELSA
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
PHARMACOKINETICS [6, 7]
Mechanism of Resistance
Indications
Dosages
METHODS OF ADMINISTRATION
SPECIAL INFORMATION AND CAUTIONS
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
QTc Interval Prolongation, Torsades De Pointes and Sudden Death
QTc Interval Prolongation, Torsades De Pointes and Sudden Death
IMMUNISATIONS
TOXICITIES [6]
DOSE MODIFICATIONS
INTERACTIONS
CONCLUSION
REFERENCES
Chapter 49:
VEMURAFENIB. ZELBORAF®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY [2, 3]
Drug Classification
MECHANISM OF ACTION
PHARMACOKINETICS
Indications
Dosages
METHODS OF ADMINISTRATION/PREPARATION
SPECIAL INFORMATIONS AND CAUTIONS
Contraindications
Elderly
Pediatric
Renal Impairment
Hepatic Impairment
Immunisations
Pregnancy
Breastfeeding
WARNINGS
Hypersensitivity
Malignancies
Hepatic Deterioration
Photosensitivity
QT Prolongation
Eye Complications
Overdosage
TOXICITIES
DOSE MODIFICATIONS
INTERACTIONS
CONCLUSION
REFERENCES
Chapter 50: VINORELBINE. NAVELBINE®
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
PHARMACOKINETICS
Mechanism of Resistance
INDICATIONS
DOSAGES
1. Advanced NSCLC, Advanced Breast Cancer and Mesothelioma [9]
Intravenous
Oral
2. Hodgkin’s Lymphoma
Intravenous
3. Desmoid Tumours
Intravenous
4. Rhabdomyosarcomas
Intravenous
5. Advanced ovarian cancer
Intravenous
METHODS OF ADMINISTRATION/PREPARATION [16]
Intravenous Administration
Oral Administration
SPECIAL INFORMATION AND CAUTIONS [16]
Contraindications
ELDERLY PATIENTS
Pediatric Patients
Immunisations
WARNINGS [16]
Myelosuppression
Hepatic Toxicity
Severe Constipation and Bowel Obstruction
Extravasation and Tissue Injury [17]
Neurological Toxicity
Pulmonary Toxicity and Respiratory Failure
Embryo-Fetal Toxicity
Contact with Eyes
TOXICITIES [16]
DOSE MODIFICATIONS [16]
Renal Impairment
Hepatic Impairment
Myelosuppression
Neurological Toxicity
Pulmonary Toxicity and Respiratory Failure
Other Toxicities
INTERACTIONS [16]
CONCLUSION
REFERENCES
Chapter 51: ZOLEDRONIC ACID, ZOMETA®,ACLASTA®, RECLAST®
ABSTRACT
INTRODUCTION
DRUG CLASSIFICATION
Mechanism of Action
Pharmacokinetics
Mechanism of Resistance
Indications [3, 4]
Dosage
METHODS OF PREPARATION/ADMINISTRATION
Special Information and Cautions
Contraindications
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
WARNINGS [3]
Bone Fractures
Hypersensitivity Reactions
Hypocalcemia
Musculoskeletal Pain
Ocular Infection
Osteonecrosis of the Jaw (ONJ)
Toxicities [3]
Dose Modifications
Interactions [3]
CONCLUSION
REFERENCES
Chapter 52:
5-FLUOROURACIL, 5-FLURACIL,FLUOROURACIL, FU
ABSTRACT
INTRODUCTION
CLINICAL PHARMACOLOGY
Drug Classification
Mechanism of Action
Pharmacokinetic [5, 6]
Mechanism of Resistance
Indications
Other Non Cancer Use
Dosage
Monotherapy Dose
Maintenance treatment
Methods of Preparation/Administration
Special Information and Cautions
Elderly Patients
Pediatric Patients
Renal Impairment
Hepatic Impairment
Immunisations
Warnings
DPD Deficiency
Hand-Foot Syndrome (Palmar-Plantar Erythrodysesthesia)
Pregnancy
Lactation
Toxicities
Interactions
Dose Modifications
CONCLUSION
REFERENCES
EDITOR’S CONTACT INFORMATION
INDEX
Blank Page
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CANCER ETIOLOGY, DIAGNOSIS AND TREATMENTS PHARMACOLOGY - RESEARCH, SAFETY TESTING AND REGULATION
THE EASY BOOK OF CANCER PHARMACOLOGY
No part of this digital document may be reproduced, stored in a retrieval system or transmitted in any form or by any means. The publisher has taken reasonable care in the preparation of this digital document, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained herein. This digital document is sold with the clear understanding that the publisher is not engaged in rendering legal, medical or any other professional services.
CANCER ETIOLOGY, DIAGNOSIS AND TREATMENTS PHARMACOLOGY - RESEARCH, SAFETY TESTING AND REGULATION Additional books in this series can be found on Nova‘s website under the Series tab. Additional e-books in this series can be found on Nova‘s website under the e-book tab.
CANCER ETIOLOGY, DIAGNOSIS AND TREATMENTS PHARMACOLOGY - RESEARCH, SAFETY TESTING AND REGULATION
THE EASY BOOK OF CANCER PHARMACOLOGY
ESTHER UNA CIDON EDITOR
New York
Copyright © 2016 by Nova Science Publishers, Inc. All rights reserved. No part of this book may be reproduced, stored in a retrieval system or transmitted in any form or by any means: electronic, electrostatic, magnetic, tape, mechanical photocopying, recording or otherwise without the written permission of the Publisher. We have partnered with Copyright Clearance Center to make it easy for you to obtain permissions to reuse content from this publication. Simply navigate to this publication‘s page on Nova‘s website and locate the ― Get Permission‖ button below the title description. This button is linked directly to the title‘s permission page on copyright.com. Alternatively, you can visit copyright.com and search by title, ISBN, or ISSN. For further questions about using the service on copyright.com, please contact: Copyright Clearance Center Phone: +1-(978) 750-8400 Fax: +1-(978) 750-4470 E-mail: [email protected]. NOTICE TO THE READER The Publisher has taken reasonable care in the preparation of this book, but makes no expressed or implied warranty of any kind and assumes no responsibility for any errors or omissions. No liability is assumed for incidental or consequential damages in connection with or arising out of information contained in this book. The Publisher shall not be liable for any special, consequential, or exemplary damages resulting, in whole or in part, from the readers‘ use of, or reliance upon, this material. Any parts of this book based on government reports are so indicated and copyright is claimed for those parts to the extent applicable to compilations of such works. Independent verification should be sought for any data, advice or recommendations contained in this book. In addition, no responsibility is assumed by the publisher for any injury and/or damage to persons or property arising from any methods, products, instructions, ideas or otherwise contained in this publication. This publication is designed to provide accurate and authoritative information with regard to the subject matter covered herein. It is sold with the clear understanding that the Publisher is not engaged in rendering legal or any other professional services. If legal or any other expert assistance is required, the services of a competent person should be sought. FROM A DECLARATION OF PARTICIPANTS JOINTLY ADOPTED BY A COMMITTEE OF THE AMERICAN BAR ASSOCIATION AND A COMMITTEE OF PUBLISHERS. Additional color graphics may be available in the e-book version of this book.
Library of Congress Cataloging-in-Publication Data ISBN: 978-1-63485-043-8 (e-book) Library of Congress Control Number: 2016935307
Published by Nova Science Publishers, Inc. † New York
CONTENTS Foreword
ix F. Lopez-Lara
Preface
xi ®
Chapter 1
Abiraterone: Abiraterone Acetate: CB7630: Zytiga A. Ballesteros
1
Chapter 2
Albumin-Bound (NAB) Paclitaxel, Abraxane® V. Arrazubi, E. Galve and P. Martínez del Prado
7
Chapter 3
Aflibercept. Zaltrap® M. López-Gómez, B. García de Santiago, E. Jiménez, A. M. Jiménez-Gordo and E. Casado
19
Chapter 4
Axitinib. Inlyta® A. Ballesteros
29
Chapter 5
Bevacizumab. Avastin® M. López-Gómez, B. García de Santiago, A. I. García, A. M. Jiménez-Gordo and E. Casado
37
Chapter 6
Bleomycin. Bleo-Kyowa. Blenoxane B. Masters
49
Chapter 7
Cabazitaxel. Jevtana® E. Una Cidon
59
Chapter 8
Cabozantinib (XL184). Cometriq® J. Molina Cerrillo, M. Gion Cortés, T. Alonso-Gordoa and E. Grande-Pulido
67
Chapter 9
Capecitabina. Xeloda® P. Diezhandino and P. Alonso
77
Chapter 10
Carboplatin. Paraplatin®. CBDCA. Diammineplatinum (II). Cis-(1,1.Cyclobutanedicarboxylato). Cis-Diammine (1,1-Cyclobutanediocarboxylato) Platinum M. Luque Cabal and P. Garcia Teijido
85
vi
Contents
Chapter 11
Cetuximab. Erbitux® M. López-Gómez, B. García de Santiago, Y. Martín, A. M. Jiménez-Gordo and E. Casado
Chapter 12
Cisplatin, Platinol®, Platinol®-AQ M. Luque Cabal and P. Garcia Teijido
103
Chapter 13
Crizotinib. Xalkori® V. Wood
113
Chapter 14
Cytarabine: Ara-C: Cytosar U: Cytosine Arabinoside: Tarabine PFS, Arabinosylcytosine, 1-Β-Arabinosylcytosine T. Cummin
123
Chapter 15
Denosumab, Prolia®, Xgeva® P. Alonso and P. Diezhandino
131
Chapter 16
Docetaxel.Taxotere® E. Galve, V. Arrazubi, P. Martínez del Prado and E. Una Cidon
139
Chapter 17
Doxorubicin Hydrochloride. Adriamycin Z. Anwar
147
Chapter 18
Enzalutamide. Xtandi®. MVD3100 J. Ching
157
Chapter 19
Erlotinib, Tarceva® S. Adeleke
165
Chapter 20
Etoposide: VP16: Vepesid: Etopophos Z. Anwar
173
Chapter 21
Everolimus. Afinitor® Y. Inam
181
Chapter 22
Gefitinib S. Adeleke
189
Chapter 23
Gemcitabine. Gemzar® P. Martínez del Prado, E. Galve and V. Arrazubi
197
Chapter 24
Imatinib. Gleevec® A. Ballesteros
207
Chapter 25
Ipilimumab J. Fra
219
Chapter 26
Irinotecan.CPT-11. Camptosar® E. Una Cidon
227
Chapter 27
Lapatinib V. Reguero Cuervo, T. Sampedro Gimeno and P. García Teijido
235
95
Contents
vii
Chapter 28
Lenvatinib, Lenvima® O. Martínez-Sáez, A. Madariaga-Urrutia, T. Alonso-Gordoa and E. Grande-Pulido
Chapter 29
Mitomycin C Mitomycin-C Kyowa [3], Mutamycin, Ametycine, Mitocin-C, Mitolem, Mito-Medac [1] Mitosol [12] M. Uherek
257
Chapter 30
Nindetanib. Vargatef® E. Una Cidon
267
Chapter 31
Nivolumab. Opdivo® E. Una Cidon
273
Chapter 32
Oxaliplatin. 1-OHP, L-OHP, Oxalatoplatin, Oxaliplatinum, Eloxatin® M. Luque Cabal and P. Garcia Teijido
281
Chapter 33
Paclitaxel: Taxol E. Una Cidon and A. Ballesteros
291
Chapter 34
Panitumumab. Vectibix® M. López-Gómez, B. García de Santiago, R. Hernández, A. M. Jiménez-Gordo and E. Casado
299
Chapter 35
Pazopanib. Votrient® A. Hernandez-Sanchez
307
Chapter 36
Pembrolizumab. Keytruda® E. Una Cidon
317
Chapter 37
Pemetrexed. Alimta® M. Uherek
327
Chapter 38
Pertuzumab. Perjeta T. Sampedro Gimeno, V. Reguero Cuervo and P. Garcia-Teijido
337
Chapter 39
Regorafenib. Stivarga® M. López-Gómez, B. García de Santiago, C. Martín, M. Caridad Miguel and E. Casado
349
Chapter 40
Sorafenib, Nexavar® E. Una Cidon
359
Chapter 41
Streptozocin. Zanosar® V. Wood
367
Chapter 42
Sunitinib. Sutent® S. Adeleke
375
Chapter 43
Trastuzumab Emtansine (TDM-1) P. Garcia-Teijido, T. Sampedro Gimeno, V. Reguero Cuervo and M. Luque Cabal
385
249
viii
Contents
Chapter 44
Temozolomide. Temodal®. Temodar®. Schs2.365. Nsc 362856 J. Ching
395
Chapter 45
Temsirolimus. CCI-779. Torisel® J. M. Roca
405
Chapter 46
Topotecan, Hycamtin® J. M. Roca
415
Chapter 47
Trastuzumab. Herceptin® P. Garcia-Teijido, T. Sampedro Gimeno, V. Reguero Cuervo and M. Luque Cabal
425
Chapter 48
Vandetanib (ZD 6474). Caprelsa P. Reguera Puertas, M. Villamayor Delgado, T. Alonso Gordoa and E Grande Pulido
435
Chapter 49
Vemurafenib. Zelboraf® A. Hernandez-Sanchez
445
Chapter 50
Vinorelbine. Navelbine® B. Masters
457
Chapter 51
Zoledronic Acid, Zometa®, Aclasta®, Reclast® P. Alonso and P. Diezhandino
469
Chapter 52
5-Fluorouracil, 5-Fluracil, Fluorouracil, Fu P. Diezhandino and P. Alonso
479
Editor's Contact Information
487
Index
489
FOREWORD The Easy Book of Cancer Pharmacology is a practical and updated guide to the antitumor drugs. The chapters of the book explain the general data of each drug used as an antineoplastic in a very simple way. The book is easy to understand and allows an immediate knowledge about the details of each drug and a prompt diagnosis of the side effects and their management. The editor and author, Dr. Esther Una Cidon, is a competent and brilliant medical oncologist, trained in Spain, and with who I have been honoured to work for a few years at the Clinical University Hospital of Valladolid. She is notorious for her strong clinical experience, continuous updating and scientific rigor. Her professional activity extends to clinical research and, as this book shows, teaching. The book is primarily aimed at residents and registrars in oncology, specialist in oncology nurse practitioners, young consultants in oncology and cancer clinical pharmacologists, and provides them with valuable information. Due to its facility and accuracy, this guide will be an essential tool for the target audience as it incorporates the latest news and updates in the dynamic field of cancer pharmacology. Prof. F. Lopez-Lara Director of the Department. Of Clinical Oncology Clinical University Hospital of Valladolid, Spain
PREFACE The Easy Book of Cancer Pharmacology represents the efforts of young oncologists, haematologists, pharmacists and oncology nurses who are highly motivated and encouraged by the significant development of new effective anticancer drugs. Since the discovery of antimetabolites and alkylating agents in the 1940s and 1950s, many new products have been introduced into our daily arsenal not only through chemotherapy agents, but also by means of biological or immunotherapeutic drugs whose side effects differ significantly. The idea of this book was born from a simple observation and confirmation of fact. New doctors in training experience high levels of stress and lack of confidence when confronting cancer patients and explaining a treatment or managing frequent side effects. Patients‘ questions will only add more nervousness, and this will lead to a failure in the doctor-patient relationship, causing the patient‘s mistrust and doctor‘s frustration. Nurses dealing with these patients will suffer pressure too, as many questions regarding antineoplastic drugs will be asked of them and patients expect them to ease their doubts. This feeling of vulnerability in front of a patient, though a part of the maturation process when becoming a professional caretaker, causes discomfort and incertitude. In this context, it is crucial to gain great knowledge about pharmacokinetic and pharmacological features of each active anticancer drug used, as well as the indications, dosages, interactions and toxicities, to be able to face the daily practice of oncology without concerns and manage daily therapeutic complications easily. This may be considered very difficult, taking into account the huge number of active agents doctors manage routinely, but doctors have accepted the challenge and designed a straightforward, comprehensible book to solve this issue. The Easy Book of Cancer Pharmacology provides the means to overcome the problem. It is conceived as an accessible, concise and yet exhaustive tool which displays a vast amounts of knowledge in a very schematic way. It is easy to consult and offers a very practical expertise to develop the ability of managing effectively each antineoplastic agent quickly. It gives the necessary insights to explain this to the patients with confidence. Each chapter reviews one active drug and shows the information with a pragmatic style, and they are divided into different sections. Each section covers distinct aspects of the agent, from general characteristics to more specific details related to clinical pharmacology.
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Esther Una Cidon
In quickly advancing fields such as oncology, tools like this book are necessary to help update the ever developing knowledge in an efficient manner. The authors are greatly appreciated for their invaluable collaboration and for having respected the spirit with which this book was written. Esther Una Cidon, MD, PhD Medical Oncologist Medical Oncology Department Royal Bournemouth Hospital NHS Foundation Trust Bournemouth, UK
To my parents, my two sisters and my uncle P. for their great support throughout my career and also in the preparation of this book
I dedicate this book to them and to those who always believed in me
In: The Easy Book of Cancer Pharmacology Editor: Esther Una Cidon
ISBN: 978-1-63485-038-4 © 2016 Nova Science Publishers, Inc.
Chapter 1
ABIRATERONE: ABIRATERONE ACETATE: CB7630: ZYTIGA® A. Ballesteros Directorate Pharmacist, Oncology, Poole Hospital Foundation Trust, Poole, Dorset, UK
ABSTRACT Abiraterone inhibits 17 α-hydroxylase/C17, 20 lyase (CYP17A1), an enzyme which is expressed in testicular, adrenal, and prostatic tumor tissues which leads to a reduction in circulating levels of testosterone. Androgen-sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with luteinizing hormone-releasing hormone analogues (LHRH) or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumour. Treatment with Zytiga® decreases serum testosterone to undetectable levels (using commercial assays) when given with LHRH (or orchiectomy) [1]. In 2011 the Food and Drug Administration (FDA) approved abiraterone acetate for use in combination with prednisone for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) who have received prior chemotherapy containing docetaxel. This approval was based on the results of a randomized placebocontrolled multicenter trial which demonstrated a statistically significant improvement in overall survival in patients receiving abiraterone acetate compared with placebo. In 2012 the FDA approved an expanded indication for the treatment of mCRPC based on a trial that randomly assigned patients with mCRPC naïve for chemotherapy to either abiraterone plus prednisone or placebo plus prednisone. Entry was restricted to patients with metastases to the bone, soft tissue, or lymph nodes. Patients with moderate to severe cancer pain or opiate use for cancer pain were excluded. All patients had a prior orchiectomy or continued to receive a gonadotropin releasing hormone analog. Radiographic progression-free survival (rPFS) was improved significantly by abiraterone. Median overall survival at the pre-specified third interim analysis was 35.3 months for abiraterone acetate and 30.1 months for placebo though not statistically significant [2].
Alejandro Ballesteros, [email protected].
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A. Ballesteros
Keywords: abiraterone, prostate cancer, castration resistant prostate cancer
INTRODUCTION Abiraterone is a structural analogue of pregnenolone (steroidal hormone manufactured primarily in the adrenal glands from its precursor, cholesterol with a number of beneficial effects) which inhibits an enzyme necessary for androgen synthesis, 17α-hydroxylase/C17, 20-lyase (CYP17) that is expressed in testicular, prostate, and adrenal tissue. It is approved for the treatment of mCRPC in patients asymptomatic or mildly symptomatic after failure of androgen deprivation therapy or patients who have progressed on docetaxel [3]. Although the activity of abiraterone is primarily confined to effects on androgen production, there is a reactive increase in corticotropin secondary to a pituitary response to the partial adrenal inhibition, which can lead to increased mineralocorticoid production. This can lead to hypokalemia and hypertension, which can be reduced by concurrent prednisone administration [2].
CLINICAL PHARMACOLOGY Drug Classification Endocrine therapy, other hormone antagonists and related agents [2].
Mechanism of Action Abiraterone inhibits 17 α-hydroxylase/C17,20 lyase (CYP17A1), an enzyme which is expressed in testicular, adrenal, and prostatic tumour tissues. CYP17 catalyses two sequential reactions: (a) the conversion of pregnenolone and progesterone to their 17-α-hydroxy derivatives by its 17 α-hydroxylase activity, and (b) the subsequent formation of dehydroepiandrosterone (DHEA) and androstenedione, respectively, by its C17,20 lyase activity [9]. DHEA and androstenedione are androgens and precursors of testosterone. Inhibition of CYP17 activity by abiraterone thus decreases circulating levels of testosterone [3]. Androgen-sensitive prostatic carcinoma responds to treatment that decreases androgen levels. Androgen deprivation therapies, such as treatment with LHRH analogues or orchiectomy, decrease androgen production in the testes but do not affect androgen production by the adrenals or in the tumour. Treatment with abiraterone decreases serum testosterone to undetectable levels (using commercial assays) when given with LHRH analogues (or orchidectomy) [2].
Abiraterone: Abiraterone Acetate
3
Pharmacokinetics [2] Absorption
Distribution
Metabolism Excretion
Time to reach maximum plasma concentration is approximately 2 hours. Administration of abiraterone acetate with food, compared with administration in a fasted state, results in up to a 10-fold (AUC) and up to a 17-fold (Cmax) increase in mean systemic exposure of abiraterone, depending on the fat content of the meal. Given the normal variation in the content and composition of meals, taking Zytiga with meals has the potential to result in highly variable exposures. Therefore, Zytiga must not be taken with food. It should be taken at least two hours after eating and no food should be eaten for at least one hour after taking Zytiga. The tablets should be swallowed whole with water. The plasma protein binding of 14C-abiraterone in human plasma is 99.8%. The apparent volume of distribution is approximately 5,630 l, suggesting that abiraterone extensively distributes to peripheral tissues. Liver metabolism due to cytochrome CYP3A4 Mean half-life 15 hours. Excreted mostly in faeces (88%)
Mechanism of Resistance Increase on intratumoral androgen synthesis and increased expression of full length and split variants of the androgen receptor [2].
Indications [2] Abiraterone indications are as follows:
The treatment of mCRPC in adult men who are asymptomatic or mildly symptomatic after failure of androgen deprivation therapy in whom chemotherapy is not yet clinically indicated. The treatment of mCRPC in adult men whose disease has progressed on or after a docetaxel-based chemotherapy regimen.
Dosages Abiraterone is available as 250 mg tablets and is administered at a dose of 1000 mg daily in combination with prednisone 5 mg administered twice daily [2].
Methods of Preparation/Administration Tablets should be taken whole, swallowed with water and on an empty stomach, with no food for 2 hours before and 1 hour after administration [2].
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A. Ballesteros
Special Information and Cautions [2] Contraindications
Hypersensitivity to the active substance or to any of the excipients listed below. Microcrystalline cellulose Croscarmellose sodium Lactose monohydrate Magnesium stearate Povidone (K29/K32) Colloidal anhydrous silica Sodium lauryl sulphate Women Severe hepatic impairment (Child-Pugh C)
Elderly Patients In a phase 3 trial of abiraterone, 71% of patients were 65 years and over and 28% were 75 years and over. No overall differences in safety or efficacy were observed between these elderly patients and younger patients. Pediatric Patients Not applicable. Renal Impairment No dose adjustment is needed in renal impairment mild to moderate. However, there are no data in patients with severe renal impairment, therefore it is recommended caution in these patients. Hepatic Impairment The use of abiraterone should be cautiously assessed in patients with moderate hepatic impairment, in whom the benefit clearly should outweigh the possible risk. Abiraterone should not be used in patients with severe hepatic impairment. Immunisations Not applicable.
Warnings [2] Mineralocorticoid Excess Use with caution in patients with a history of cardiovascular disease. The safety of abiraterone in patients with left ventricular ejection fraction (LVEF) 1/100 to