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.

Appendix

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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References

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