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183C.W. Penteado Schmidt, F.G. Menezes, Drug Therapy and Interactions in Pediatric Oncology,DOI 10.1007/978-3-319-38872-4,© Springer International Publishing Switzerland 2017
Appendix
This appendix provides an overview of essential things to know in pediatric oncology practice, such as how to calculate body surface area in children, and how to calculate the carbo-platin dose using the area under the curve and the estimated creatinine clearance.
A glossary of terms used in the book is also provided.
List of tables
Table 1 Constant of Proportionality for Estimated Creatinine Clearance
Body Surface Area (BSA) [4]
The body surface area (BSA) is a mathematical relationship, expressed in m2, with the result obtained from the height and weight of the patient. This measure is used in order to obtain a more comprehensive parameter of the patient’s weight, to define more appropriate dosage. The BSA is widely used in oncology; the majority of protocols specify the dose in m2.
BSA (m2) = Weight kg Height cm( ) ´ ( ) ´( )0 425 0 725
71 84
10 000
. ..
,
184
Table 1 Constant of Proportionality for Estimated Creatinine ClearanceAge K<1 year (preterm) 0.33
< 1 year (full-term) 0.45
1–12 years old 0.55
13–21 years old, female 0.55
13–21 years old, male 0.70
Source: Based on information from Bragalone [4, 66]
log BSA (m2) = log . log . .
,
kg cm´( )+ ´( )+0 425 0 725 1 8564
10 000
DuBois Formula: BSA (m2) = Height cm Weight kg( )´ ( )
3 600,
Calculation of Carboplatin Dose
Carboplatin is excreted almost entirely by glomerular filtration; therefore, it has a half-life that is highly correlated with the clas-sification of glomerular filtration, and the area under the curve (AUC) is essential for the determination of the individual patient dose. Therapy may be optimized by being based on a wide vari-ety of methods of analysis of renal clearance. Studies of doses and chemotherapy protocols often use the AUC for calculate carboplatin doses, and these doses are not described in m2 [1].
Carboplatin dose in mg = Desired AUC × (25 + measured or estimated creatinine clearance) [4].
Estimated Creatinine Clearance [4]
This measure is used for patients with normal renal function, except when the serum creatinine changes quickly or when the patient has marked edema. Indicated only for children over 6 months old.
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185
Creatinine clearance (mL/min/1.73 m2) = K × Height (cm)/Scr (mg/dL)
Scr: Serum creatinine in mg/dLK: Constant of proportionality, as shown in Table 1The following formula can be applied for children and
adolescents between 1 and 18 years old: Crcl (mL/min/1.73 m2) = 0.48 × Height (cm)/Scr (mg/dL)
Appendix
187C.W. Penteado Schmidt, F.G. Menezes, Drug Therapy and Interactions in Pediatric Oncology,DOI 10.1007/978-3-319-38872-4,© Springer International Publishing Switzerland 2017
Aminoglycosides Class of bactericidal antibiotics that act by inhibition of bacterial protein synthesis; examples are ami-kacin, gentamicin, neomycin, and tobramycin.Anthracyclines Class of antineoplastic drugs with various mechanisms of action; this class includes doxorubicin, dauno-rubicin, and idarucibin.Antibiotics derived from penicillin Class of antibiotics that includes many drugs derived from penicillin; most commonly used are amoxicillin and ampicillin.ATRA (trans-retinoic acid) syndrome Characterized by fever, pulmonary infiltrates, pleural or pericardial effusion, and renal failure. It may occur usually 2–10 days after treat-ment and is reversible with the temporary suspension of ATRA and treatment with dexamethasone 0.5–2 mg/kg.Auer rods Auer rods are lysosomal compounds that can be seen in the blasts of some acute leukemias of myeloid lineage; they contain peroxidase, lysosomal enzymes, and large crys-talline inclusions.Azole antifungals Class of antifungals (fungistatics), with a broad spectrum of action; examples are fluconazole and voriconazole.Bcr-abl protein (hybrid) This protein is the result of trans-location between the long arms of chromosomes 9q34 and 22q1 (Philadelphia chromosome); this protein has increased tyrosine kinase activity.
Glossary
188
Chloroma Chloroma is the same as granulocytic sarcoma and extramedullary myeloid tumor, which is a tumor of myeloblasts or immature myeloid cells that appears in extra-medullary locations.Cytochrome P450 Family of metabolizing enzymes.Down syndrome Most cases are caused by trisomy of chro-mosome 21, but cases can occur by the translocation of chro-mosome 21 and other chromosomes.Dynamic equilibrium Dynamic equilibrium occurs when there is linearity and constancy in the bioavailability of a drug.Echinocandins Class of antifungal drugs that inhibit the synthesis of β-d-glucan in fungal cell walls. Exemples of echi-nocandins are micafungin and caspofungin.Free drug Drug that is not bound to a protein or enzyme.Hydrophobic substances These are non-polar; they tend to not mix with water.Hydrolytic substances These are polar; they tend to mix with water.Isoenzymes Enzymes that differ in amino acid sequence and catalyze the same chemical reactions.Lymphocyte predominant cells Called popcorn cells, lym-pho-histiocytic cells, or LP cells. These are a variant of Reed Steinberg cells, which exhibit a lobed and bent nucleus, with inconspicuous nucleolus.Macrolides Class of antibiotics that inhibit bacterial protein synthesis. Their action can be bacteriostatic or bactericidal (at high concentrations or depending on the microorganism).Narrow therapeutic dose This is the area between the mini-mum effective dose and the maximum dose.Pancytopenia Reduction of leukocytes, erythrocytes, and platelets; all reduced at the same time.pH Potential of hydrogen, used to measure acidity or alkalinity.Philadelphia chromosome This chromosome is the result of translocation between the long arms of chromosomes 9q34 and 22q1.pKa Acid dissociation constant.
Glossary
189
Platinum compounds Class of drugs, with many mechanisms of action, such as carboplatin and cisplatin.Reed Sternberg Cells Clonal B-lymphocytes that do not produce immunoglobulin nor possess functional B-receptors; they are giant cells, bi- or multinucleated.Stem cell This is an undifferentiated cell that can undergo differentiation to a specific type of cell.Vinca alkaloids Class of alkaloid drugs, such as vincristine, vinblastine, and vinorelbine, extracted from a plant called vinca.Xenobiotics Compounds synthesized industrially and not found in nature.
Glossary
191C.W. Penteado Schmidt, F.G. Menezes, Drug Therapy and Interactions in Pediatric Oncology,DOI 10.1007/978-3-319-38872-4,© Springer International Publishing Switzerland 2017
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201C.W. Penteado Schmidt, F.G. Menezes, Drug Therapy and Interactions in Pediatric Oncology,DOI 10.1007/978-3-319-38872-4,© Springer International Publishing Switzerland 2017
Index
Symbols & Numbers 3q27 , 139 4-Hidroxifosfamide , 159 4-Hydroxy-ifosfamide , 144 4q22 , 139 5HT3 antagonists , 153 6-Mercaptopurine , 71, 72, 74, 80,
83, 86, 91–93, 99, 144, 171, 174, 177
6-Methylmercaptopurine nucleotide (6-MMPN) , 171
6-Thioguanine , 59, 65, 66, 85, 97, 98
6-Tiouric acid , 171 7 + 3 (protocol) , 58 7p21 , 139 8 in 1 (protocol) , 101–103 13q32 , 139 16p13.1 , 139 17q21.3 , 139
A α1-acid glycoprotein (AAG) ,
135–136 ABC , 139, 140
genes , 139 transport protein , 136–140
ABCB1 , 139 inducers , 153
ABCC3 , 139 ABCC4 , 139 ABCC5 , 139 ABCC6 , 139 ABCG2 , 139 Abdominal pain , 161, 163 Absorption , 126, 127, 129, 131,
155, 160, 174, 177 ABVD (protocol) , 51, 52 ABVE-PC (protocol) , 54 Acetylation , 128 Acid characteristic , 148 Acid drug , 135, 144, 148 Acid protein , 135 Acrolein , 144 Acute leukemia , 3 Acute lymphoblastic leukemia
(ALL) , 2, 7, 24, 108–114 Acute lymphoid leukemia
(ALL) , 8, 15, 17, 20, 25, 69–99
IC-BFM 2002 (protocol) , 87–99
L3 , 115–121 Acute myeloid leukemia (AML) ,
15, 24, 25, 58–68 Addition , 130 Additive effect , 130, 162, 167 Additive nephrotoxic effect , 164 Adolescents , 3
202
Adrenal cortical hormone , 128 Adults , 4 Africa , 15, 17–19 African children , 18 Agonist , 129 AIDS , 18, 19 Albumin , 127, 128, 135
serum albumin , 127, 129 Aldehyde dehydrogenase
1A1 , 144 Aldoifosfamide , 144 Aldophosphamide tautomer , 144 Alkaline
pH , 144 urine , 148
Alkalinization of urine , 144 Allopurinol , 171 Americas , 20 Amikacin , 161 Amino acids , 139 Aminoglycoside antibiotic ,
161, 164 Amphotericin B , 167, 169 Anabolism , 171 Analgesics
narcotic , 153 non-opioid , 153
Anemia , 139 Antacid , 155, 160 Antagonism , 130
chemical antagonism , 130, 131
functional antagonism , 130, 131
physiological antagonism , 130, 131
processing , 130 Antagonist , 128, 154 Antagonize , 155 Anthracycline , 51, 139, 142 Antibiotic drugs , 162–166 Antibiotics derived from
penicilin , 162, 165 Anticonvulsants , 146–147 Antiemetic drugs , 148, 154–155 Antifungals , 167–170
Anti-infl ammatory drugs , 147–153
Anti-infl ammatory (nonsteroidal) , 147–148, 149
Antimicrobial , 125, 161–167 in tuberculosis , 162
Aprepitant , 154–157 Area under curve (AUC) , 154,
159, 161, 163, 180 Arthralgia , 147 Asia , 19–20 Asian children descendants , 8 Asparaginase , 70, 73, 76, 78, 79
L-asparaginase , 82, 84, 90, 94–98
Aspirin , 149 ATP-binding cassette
transporters , 139–140, 155, 160
ATRA syndrome , 67, 68 Atria , 142 Auer rods , 59 Australia , 24 Austria , 7 AVD (protocol) , 105 Azithromycin , 161, 163 Azole antifungal , 167–170
B Baby brain I (protocol) , 101 Bangladesh , 20 Barbiturates , 147 Basic drugs , 135 B-cell precursor ALL , 88, 89,
91, 92 BCR-ABL , 147 BEACOPP (protocol) , 55 Beijing , 20 Benefi cial drug interactions ,
141–145 Berlin-Frankfurt-Münster
Group , 87 BFM2004 (protocol) , 58–68 BFM95 (protocol) , 69–80 Bile salts , 139
Index
203
Bind , 148 Binding proteins , 132–136 Bioavailability , 173, 174, 177 Biotransformation , 126, 128, 131
by enzyme induction , 129 by enzyme inhibition , 129
Black children , 15, 18 Blast cells count , 81 Blast crisis , 56, 58 Blasts , 60, 61, 67, 69, 88, 115 Bleomycin , 51–55 Blocker of receptor-2 of
histamine , 155, 160 Blood count , 69 B non-Hodgkin lymphoma ,
108–114 Body surface area (BSA) , 130,
132, 135, 179–180 Bone marrow , 55, 81, 115
examination of , 60 induction , 60 puncture , 61, 62
Bone tumors , 3, 4 Boys , 8, 19 Brain , 8
and spinal tumors , 4 tumors , 8, 15, 16, 100–104
Brazil , 16, 17 Brentuximab vedotin , 133, 137 Burkitt lymphoma , 3, 18, 24,
115–121 Busulfan , 133, 161, 163
C Calcium , 174, 177 California , 15 Canada , 15 Cancer
deaths , 17 diagnosis , 3, 17 treatment , 3, 17
Carbamazepine , 146 Carboplatin , 122, 180 Carboxy-ifosfamide , 144 Carboxylesterases , 145
Carcinomas neoplasms , 4 Cardiac chambers , 142 Cardiac muscle fi ber , 142 Cardiomyocytes , 142 Cardiomyopathy , 142 Cardiotoxicity , 51, 142, 143 Caribbean , 1, 2, 21–23 Caspofungin , 168, 169 Catabolism (intracellular) , 171 Catalysis , 144 Catalyze , 145 CAV-P/VP (protocol) , 104 CCDE (protocol) , 106 Ceftriaxone , 162, 164 Cell membranes , 142 Central Africa , 19 Central America , 1, 2, 20–23 Central Europe , 7 Central nervous system (CNS) ,
8, 11–13, 66, 69, 115 disease , 95, 97, 98, 115 involvement , 89 tumors , 4, 16, 19, 20
Cerebrospinal fl uid , 115 Chemotherapeutic drugs , 25 Chemoytherapy , 173–177 Child cancer , 26 Childhood cancer mortality , 24 Childhood of 0 to 14 years old , 4, 9 Children
ages 1 to 14 years , 2, 11, 18, 24 10 and 14 years old , 2, 9, 13,
15, 16 between 0 and 14 years , 16, 24 between 1 and 19 years , 16 between 1 and 4 years old , 11 between 5 and 9 years old ,
2, 12 between 15 and 19 years old ,
2, 14 of 0 year old , 18 under 1 year old , 2, 10 under 15 years old , 17
Chloroacetaldehyde , 144 Chronic myeloid leukemia
(CML) , 55–58, 147
Index
204
Chronic phase , 55 Cisplatin , 101–104, 106, 123,
167, 169 Clarithromycin , 161 Clearance , 131, 147, 154, 158, 161,
174–176 Clearance of creatinine (Clcr) , 181
estimated clearance , 180–181 serum creatinine , 180, 181
Clear cell sarcoma of kidney , 3 Clinical practice , 25 Clinical protocols , 141–145 c-myc oncogene , 18 CODOX-M (protocol) , 107 Competitive inhibition , 131, 132 Concentration (drug) , 129, 132 Conjugation , 128 Constant of proportionality for
creatinine clearance estimated , 180
Constipation , 161 Contractile function , 144 Contraindicated interactions , 127 COPDAC (protocol) , 52 COPE (protocol) , 101 COPP/ABV (protocol) , 53 COPP (protocol) , 52 Corticosteroids , 168 Costa Rica rate , 21–23 Costs , 16
fi nancial cost of cancer , 4 health care, investments in , 17
Cow’s milk , 174, 177 Cranial nerve paralysis , 115 Cuba , 21, 23 CVP (protocol) , 55 Cyclophosphamide , 52–55, 71, 74,
75, 83, 85, 91, 94, 97, 98, 100, 101, 103, 104, 106–110, 113, 114, 116–118, 120, 121, 133, 144, 147, 156, 158, 175, 176
Cyclosporine , 168, 170 CYP , 131, 132, 145, 148, 173, 174 CYP450 , 126, 128, 131–132, 136,
144, 146, 162
CYP1A2 , 147, 149, 174 CYP1A6 , 147 CYP2A1 , 132, 135 CYP2A4 , 168 CYP2A6 , 133, 147, 151 CYP3A4 , 128, 132, 133, 135, 147,
149, 151, 154, 156, 158, 161–165, 169, 170, 173–176
CYP3A7 , 132 CYP2B6 , 133, 147, 149, 151 CYP2C , 132, 135 CYP2C8 , 133, 147, 149, 154, 156 CYP2C9 , 133, 147, 149, 151, 154,
156, 162, 164, 165, 168–170, 174–176
CYP2C19 , 133, 147, 149, 151, 154, 162, 164, 165, 168–170
CYP2CP , 168 CYP2D6 , 132, 133, 135, 149, 153,
174–176 CYP2E1 , 132, 133, 135, 149 CYP Polymorphisms , 173 Cystic fi brosis , 139 Cystitis
hemorrhagic cystitis , 144 prophylaxy , 71, 74, 76
Cytarabine , 59, 60, 62, 64–66, 68, 71, 74, 76, 78, 79, 82–85, 87, 91, 94–98, 102, 103, 107–114, 116, 117, 119, 120
high dose , 61, 63, 64, 111, 112, 119
Cytochrome. See CYP Cytosol , 145 Cytotoxic effects , 142
D Dacarbazine , 51, 52, 102, 133 Dactinomycin , 105 Daunorubicin , 70, 78, 82, 88, 90,
95, 137, 158 DBVE (protocol) , 54 Death , 3, 4, 9, 16–20 Deoxythymidine monophosphate
(dTMP) , 142
Index
205
Deoxyuridine monophosphate (dUMP) , 142
Detoxifi cation pathway , 144, 145 Developed countries , 3 Developing country , 3, 16, 17 Dexamethasone (DEXA) , 68, 73,
75–80, 82, 84, 87, 94–98, 148, 151, 154–155, 158, 159
Dexrazoxane , 142–144 Diastolic dysfunction , 144 Diclofenac , 147, 149 Dihydrofolate , 166
reductase enzyme , 141, 142, 166, 167
Dimesna , 144 Distribution , 127, 129, 131 DNA synthesis , 142 Docetaxel , 133, 156, 158, 175, 176 Dominican Republic , 21, 23 Down syndrome , 59, 66 Doxorubicin , 51–55, 73, 84, 97, 98,
100, 104–107, 109, 110, 113, 114, 117, 118, 120, 121, 123, 133, 137, 142–144, 153, 156, 158, 175, 176
Drop-out rate , 23 Drug clearance , 144 Drug-drug interactions , 126,
131–140 Drug interaction , 25, 26, 126–137,
147–156, 158, 160, 163–166, 175–177
Drug-parenteral nutrition interaction , 127
Drug resistance , 139 DuBois formula , 180 Dynamic equilibrium , 127
E East Asia , 19 East Asian ethnic origin , 15 Eastern Asia , 20 Eastern Europe , 7, 8 Echinocandins , 168, 169 Economic impact , 4
Edema , 180 Effl ux (by proteins) , 155, 161, 163 Egypt , 19 Elimination , 127, 128, 155, 160 El Salvador , 21–23 Embryonal tissues , 2 Embryonal tumors , 9 Endoplasmic reticulum , 131, 145 England , 9 Enzyme , 128, 131, 132, 142, 145,
147–149, 151, 162, 171 complex , 133, 148–153, 169,
175, 176 conditions in neonate
patients , 135 degradation , 144 hydrolytic enzymes , 145 inducers , 148 induction , 128 inhibition , 128, 156, 157 inhibitors , 131, 148 metabolism , 165
Epipodophyllotoxins , 139 Epithelial
neoplasms , 4 tumors , 3
Epstein-Barr virus , 18, 24 Erythromycin , 161 Esophageal refl ux , 155 Ester , 145 Ethnic groups , 8 Etoposide , 53–55, 60, 64, 79, 96,
101, 104, 106, 111, 112, 114, 119, 120, 122, 133, 137, 147, 156, 158, 175, 176
Europe , 1, 2, 4–9, 16, 20 European populations , 5 European Union , 19, 24 Ewing sarcoma , 3, 19 Excretion , 126, 128, 129, 131, 144 Eye drops , 62, 64, 65
F Facial tumor , 115 Fetal livers , 132
Index
206
Fever , 68 Filgrastin , 68 Filtration , 128, 129
glomerular fi ltration rate , 132, 135, 180
First few years of life , 9 First-pass metabolism , 171 Five-year survival rate , 2, 7, 17,
20, 24 FLAG (protocol) , 68 Fluconazole , 169, 170 Fludarabine , 68 Folate , 141 Folic acid , 174, 177 Folinic acid , 83, 86, 107,
117–121, 141 Food , 173–177 Free drug concentration ,
127, 129 Free radicals of oxygen , 142
G Gastric emptying , 127, 155, 160 Gastritis , 155 Gastrointestinal absorption , 127 Gastrointestinal motility , 127 GBTLI ALL-99 (protocol) ,
80–87 Gene , 139, 167 Genetic disorders , 139 Gentamicin , 161 Germany , 4, 7 Germ-cell , 4 Girls , 8, 19 Glioma , 167, 169 Glucuronidation , 128 Glutathione , 128 Gonadal neoplasms , 4 Granulocytes , 69 Grapefruit , 173, 176 Great Britain , 2, 8, 9 Growth hormone , 127 Guatemala , 21, 23
H Half-life (of a drug) , 180 Hawaii , 15 Hawaiian , 15 HD-CAV (protocol) , 100 Health policy , 17 Hearing , 161, 164 Heart , 144 Heart muscle , 142 Height , 179, 181 Hematological diseases , 1, 23 Hematological effects , 162 Hemato-oncological
disorders , 23 Hematuria , 167, 169 HEMORIO , 58–68 Hepatic and hematologic
toxicities , 86 Hepatic carcinomas , 18 Hepatic effects , 162 Hepatic metabolism , 132, 135 Hepatic tumors , 4 Hepatitis B and C , 18, 19 Hepatoblastoma , 3, 9, 16, 123 Hepatocellular carcinoma , 9, 16 Hepatocytes , 127, 131 Hepatotoxicity , 170 Hepatotoxins , 127 High-risk protocol (HR12) , 69 Hodgkin lymphoma , 3, 8, 15, 16,
18, 20, 24, 51–55 Honduras , 21, 23 Hong Kong , 19 Hydration , 144 Hydrocortisone , 82–85, 87,
108–113, 116, 117, 119, 120, 151
Hydrogen peroxide , 142 Hydrolysis , 128, 145 Hydrophobic compounds , 131 Hydroxylation pathway ,
131, 144 Hydroxyurea , 56–57, 102, 103 Hyperalbuminemia , 135
Index
207
I Ibuprofen , 147, 148, 150 ICCC (International Classifi cation
of Childhood Cancer) , 4, 9, 11–14
ICE (protocol) , 122, 123, 133, 144, 156, 158, 175, 176
IDA-FLAG (protocol) , 68 Idarubicin , 60, 62, 66, 68, 137, 158 Ifosfamide , 77, 95, 122 Ifosfamide mustard , 144 IgH , 81 Imatinib , 55–58, 133, 147–148,
154, 155, 160, 168 Immunodefi ciency , 18, 24 Imunnophenotyping , 81 Incidence rates , 3 India , 19, 20 Induce , 144, 146–153, 162
enzymes , 148 Inducer , 129, 137, 146–148,
154, 173 drug , 128
Induction , 59, 128, 132, 154, 164 Inductor , 131, 149, 151, 152, 158 Infant aged under a year , 19 Infant death , 16 Inhibition , 141, 144, 148–154, 161,
163, 165–167, 169, 170 enzymes , 153
Inhibitor , 137, 145, 146, 149–154, 162, 168–170, 173, 174
Inhibits , 171 Insulin , 127 Interaction , 25, 26, 125–127, 136,
146–148, 154, 160–162, 165, 167–169, 174–177
low interactions , 127 moderate interactions , 127 serious interactions , 127
International Classifi cation of Disease (ICD) , 4
Intestinal constipation , 163 Intestinal infectious diseases , 19
Intoxication , 144, 163 Intracranial mass , 115 Intracranial neoplasms,
miscellaneous , 11–13 Intracranial tumors , 8 Intraspinal neoplasms,
miscellaneous , 11–13 Intrathecal , 60, 61, 63–66, 82–85,
87, 97, 98, 111, 112 MADIT , 76, 78, 79
Invasive cancer , 11–14 incidence , 9, 10
Inversion of chromosome (16) , 59 Ions , 139 IPA (protocol) , 123 Irinotecan , 134, 138, 139, 144, 147,
156, 159, 168, 175, 176 Iron-doxorubicin complex , 142 Iron ions , 142 Isoenzymes , 128, 132 Isoniazid , 162, 165 Isophosphoramide mustard , 144 Itraconazole , 170
J Japan , 19 Japanese children , 19 Jaw pain , 161, 163
K Kaposi’s sarcoma , 18 Kidney , 131, 135, 144 Kinase inhibition , 147 Kuwait , 20
L Latin America , 16–17 Lethality (high) , 25 Leucovorin , 72, 77, 92–95,
109–113, 141–142 Leukemia , 4, 8–16, 19, 20, 24, 87
Index
208
Leukocyte , 56, 61, 66, 69 count , 56, 59, 66
Liposoluble , 128 Liposomal morphine , 153 Liver , 127, 128, 147
cirrhosis , 167 enzymes , 146
LMB86 (protocol) , 108–114 LMB89 (protocol) , 115–121 Lomustine , 102, 103, 134, 175, 176 Lung cancer , 139 Lymphocyte predominance , 15 Lymphoma , 4, 13, 14, 18, 20, 24
M m 2 , 179, 180 M0 AML , 59 M1 AML , 59 M2 AML , 59 M3 AML , 59 M4 AML , 59 M5 AML , 59 M6 AML , 59 M7 AML , 59 Macrolide , 161, 163 MADIT , 76, 78, 79 Malaria , 18, 19, 24 Malignant neoplasm , 18 Malignant tumors , 16 MAO inhibitors , 153 Maori , 24 Mediastinal tumor , 69 Medulograma , 69 Melanoma (malignant) , 24 Melanotic neuroectodermal
tumor , 3 Meloxicam , 150 Melphalan oral , 174, 177 Mesna , 71, 74, 76, 77, 83, 85, 122,
144 Metabolism , 128, 129, 156, 157,
161, 163, 168 Metal ions , 142 Metamyelocytes , 56 Methadone , 153
Methotrexate , 54, 70–75, 77–80, 82–88, 90–99, 107–113, 116, 117, 119–121, 138, 139, 141–142, 144–145, 148, 155, 160, 162, 165–167, 169, 174, 177
high dose of methotrexate (HD MTX) , 109, 110, 111, 112, 113, 117, 119, 121
Methylation , 128 Methylene-tetrahydrofolate , 142 Methylprednisolone , 102, 103 Metoclopramide , 135 Mexico , 20 Micafungin , 168, 170 Mitochondria , 142 Mitochondrial enzymes , 142 Mitoxantrone , 61, 63, 66, 139 Modulation , 25 Morocco , 19 Morphine , 153 Mortality rates , 15, 20, 24 Mucositis , 162, 165 Multidrug , 139 Multidrug resistance gene
complex (MDR) , 81 Multivitamin , 174, 177 Muscle cramps , 147 Musculoskeletal complaints , 147 Myalgia , 147 Myeloblasts , 56 Myelocytes , 56 Myelodysplasic diseases , 9–14 Myeloproliferative disease , 9–14 Myelosuppression , 162, 165, 167 Myocyte damage , 144
N NADH dehydrogenase , 142 Narrow therapeutic , 132
index , 25 window , 25
Nasopharyngeal carcinoma , 18, 24
Nauseas , 154
Index
209
Neonatal , 132, 135 Neonates , 126
dose adjustment in , 135 Nephrotic syndrome , 135 Nephrotoxic drug , 162, 167, 169 Nephrotoxicity , 161, 162, 164, 165 Neuroblastoma , 10, 17, 19,
100, 104 Neurokinin 1 (NK1) , 154 Neurological disorders , 139 Neurotoxicity , 168, 169 Neutrophil count , 107 Newborns , 130, 132, 135 New Zealand , 24 Nicaragua , 21–23 Nitric oxide , 142 Nodular sclerosing histology , 15 Nodular sclerosis , 8, 15 Non-competitive inhibition , 132 Non-Hodgkin lymphoma , 3, 18,
24, 106–108 Non-malignant tumors , 4 North America , 9–17 Northern Europe , 7 Northern hemisphere , 24 Nucleoside , 139 Numbness , 161 Nutrition , 127 Nutritional supplements , 174
O Oceania , 20, 24–25 OEPA (protocol) , 53 Older children , 3 Omeprazole , 155, 160 Ondansetron , 154 Opioid , 153 Opioids , 153 OPPA (protocol) , 53 Organic anion transporter-1
(OAT-1) , 147 Organic cation transporter-1
(OAT-1) , 147 Osteosarcoma , 18, 121–122 Ototoxicity , 161, 164
Oxidation , 128 metabolism , 128 pathways , 144 stress , 142
P Paclitaxel , 134, 138, 157, 159,
175, 176 Pain , 161, 163
management of , 153–154 Papua New Guinea , 24 Paralytic ileus , 161, 163 Paresthesia , 163 Passive diffusion , 142 PCR , 81 P450 cytochrome , 128 Peginterferon , 153 Penicillin inhibits , 162, 165 P450 enzymes , 131 Pericardial effusion , 68 Peripheral nervous cell
tumors , 10 P-glycoprotein , 136–138, 151, 153,
154, 158, 161–164, 169, 170 modulation , 148, 154
pH , 127, 129 of stomach , 155, 160 of urine , 148
Pharmaceutical form , 127 Pharmacodynamic , 25, 126,
132, 139 interaction , 128–131, 142
Pharmacokinetic , 25, 126, 131–140, 146, 167, 168
interactions , 127–128, 130 Pharmacological activity , 25 Pharmacological treatment ,
25–26 Phase I reactions products , 128 Phase II reactions products , 128 Phenobarbital , 146, 147 Phenylbutazone , 135 Phenytoin , 146, 147 Philadelphia chromosome (Ph) ,
56–58, 89
Index
210
Phosphoramide mustard , 147 Phytotherapeutic drugs , 173 pKa , 135 Plasma , 127, 132, 135, 139
binding sites , 127 concentrations , 161, 163, 167 protein , 126, 128, 129,
132–136, 166, 167 Plasmatic , 145 Platelet , 56, 62, 64, 66
count , 69 Platinum , 162
compounds , 161, 162, 164, 165 Pleural effusion , 68 PMN , 63, 64 Polymorphonuclear neutrophil , 62 Popcorn cells , 27 Posaconazole , 169, 170 Potentialization , 130, 165 Precursor lesions , 3 Prednisolone , 52–55, 70, 82, 90,
94–96, 108–110, 113, 114, 116–118, 120, 121, 135, 152
good response , 88 poor response , 88, 89
Premature , 130, 132, 135 Pre-school children , 3 Prevention, current policies , 16 Primary health provides , 3 pro-B ALL , 89 Procain , 153 Procarbazine , 52, 53, 55, 102, 103 Processing antagonism , 131 Prodrug , 126, 144, 145, 171 Prognosis , 8 Pro-myelocytes , 56 Prophylaxis , 168 Propranolol , 135 Protein , 127, 129, 135, 136, 147,
148, 151, 163, 169 of effl ux , 160
Proton pump inhibitors , 155, 160, 168
Proximal tubular secretion , 162, 165
Psoriasis , 148
P450 system , 128 Puberty , 130 Public health , 19
issue , 8 priority , 3, 19, 20
Pulmonary fi brosis , 51, 161, 163 Pulmonary infi ltrates , 68 Pulmonary toxicity , 167
R Radiotherapy , 65 Reactive metabolite , 131 Receptor , 129, 154 Reduction , 128 Reinduction , 166, 167 Renal effects , 162 Renal elimination , 132, 135 Renal failure , 68, 161, 162, 165 Renal function , 132, 180 Renal tubular
excretion , 166 secretion , 166, 167
Renal tubules , 144 Renal tumors , 4 Renal uptake , 147 Rescue with leucovorin , 75 Research , 4 Resistance
of antineoplasic therapy , 139 Reticuloendothelial neoplasms ,
4, 13, 14 Retinoblastoma , 3, 4, 17, 18, 106 Rhabdoid tumor (malignant) , 3 Rifampicin , 162, 164
S Salicylates , 148 Seizures , 153 Senegal , 19 Serotonin syndrome , 153 Serum concentration , 167 Serum dosage , 167 Serum level , 168 Sialic acid , 135 Sirolimus , 168
Index
211
Small round cell tumours , 3 SN-38 (metabolite of
irinotecan) , 147 Socio-economic development , 8 Sodium bicarbonate , 144–145 Soft-tissue sarcomas , 4 Solid tumors , 1, 2, 22, 23, 100, 122 South Africa , 18 South America , 16 South Asian ethnic origin , 8 Spinal cord , 115 Spinal puncture , 64 Splanchnic blood fl ow , 127 Stem cell transplantation , 55, 56,
59, 68, 89 Steroidal anti-infl ammatory
drugs , 151 Steroid hormones , 139, 173 St. John’s Wort , 173–175 Stomach upset , 155 Structural analogue , 174, 177 Sub-Saharan Africa , 17 Sub-Saharan African registries , 18 Substance P , 154 Substrate , 128, 129, 131, 133,
137, 139, 147, 149–154, 156–158, 168
Sub-tropical Africa , 18 Sucralfate , 155, 160 Sulfa drugs , 166, 167 Sulfamethoxazole , 167
with trimethoprim , 166 Sulfation , 128 Sunlight (exposure) , 24 Superoxide , 142 Supplements , 174 Supportive care , 127 Supportive drugs , 125 Survival , 8
differences in , 8 time , 2 at 5 years , 8
Sympathetic nervous system , 4, 8, 15
Synergic effect , 130 Synergism , 130
T Tacrolimus , 168, 170 Tanzania , 18 T-cell ALL , 88, 89, 91, 93 TCR , 81 Temozolamide , 174, 177 Testosterone , 127 Tetrahydrofolate , 166 Therapeutic effi cacy , 25 Thiol group , 144 Thiopurine methyltransferase
(TPMT) , 171 Three-year survival rate , 20 Thyroid hormone , 127 Tissue , 127, 129, 136, 144 Topoisomerase , 145 Topotecan , 139 Toxic , 25, 86, 127, 130, 132, 142,
145, 154, 162 Toxic additives , 164
effect , 161, 162, 165 Toxical mechanism of
doxorubicin , 142 Toxic effects , 162, 167 Toxicity , 25, 51, 127, 129–131,
139, 140, 144, 146, 148, 156, 157, 161, 163, 165, 168, 173, 174
poisoning , 161 Toxic metabolites , 144 Tramadol , 153 Translocation of chromosomes
(8; 21) , 59 Transplantation , 64
autologous transplantation , 55 stem cell transplantation , 55,
56, 59, 68, 89 Transport proteins , 136–140 Trans retinoic acid , 67 Tretinoin , 67 Trimethoprim , 167 Trophoblastic neoplasms , 4 Tropical Africa , 18 Tuberculosis , 18 Tubular secretion , 128, 129 Tumor prognostic factor , 139
Index
212
U Undifferentiated tumors , 3 United States , 2, 7, 9–16 Unreported , 3 Urine
alkalinization , 144 fl ow , 128, 129 pH , 128, 144
Urotoxic , 144
V Valproic acid , 146 VAMP , 54 Vancomycin , 162, 165 Venezuela , 17 Veno-occlusive disease , 161, 163 Ventricles , 142 Ventricular ejection , 142 Vietnam , 20 Vinblastine , 51–55, 78, 134, 138,
157, 159, 161–163, 175, 176
Vinca alkaloids , 164, 165, 168, 169
Vincristine , 52–55, 70, 73, 75, 80, 82, 84, 87, 90, 94, 97, 98, 100–105, 107–110, 113, 114, 116–118, 120, 121, 134, 138, 159, 161–163, 175, 176
Vindesine , 95
Vinorelbine , 134, 157, 159, 161, 163, 175, 176
Vitamins , 139 Vomits , 154 Voriconazole , 167–170
W Wales , 9 Warfarin , 135 Weight , 179 Western Europe , 8 West Indian , 8 West of Europe , 8 White blood cell
count , 66, 67, 80–81, 88, 89 levels , 57
White children , 8, 15 White populations , 8, 15, 20, 24 Wilms tumor , 3, 8, 15, 18, 19,
104–105
X Xanthine oxidase , 142, 174, 177 Xenobiotics , 131
Y Young adults , 3 Young Europeans , 1, 6
Index