Chemotherapy in Neonates and Infants

210 Pages·2018·1.689 MB·English

by  Carolina Witchmichen Penteado Schmidt

Carolina Witchmichen Penteado Schmidt
Chemotherapy in
Neonates and Infants
Pharmacological
Oncology for Children
Under 1 Year Old
123
Chemotherapy in Neonates
and Infants
Carolina Witchmichen Penteado Schmidt
Chemotherapy in
Neonates and Infants
Pharmacological Oncology for
Children Under 1 Year Old
Carolina Witchmichen Penteado Schmidt
Curitiba
Paraná
Brazil
ISBN 978-3-319-70590-3 ISBN 978-3-319-70591-0 (eBook)
https://doi.org/10.1007/978-3-319-70591-0
Library of Congress Control Number: 2018931380
© Springer International Publishing AG, part of Springer Nature 2018
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Preface
There are few publications about use of chemotherapy in
neonates and infants, and even fewer about what to do and
what cannot be done in daily practice. The purpose of this
book is to provide a guideline for drug therapy in children
under 1 year old, according to each week or month of the
patient’s life. This book provides guidance for physicians,
pharmacists, and other health care professionals directly
involved in chemotherapy for pediatric patients under 1 year
old. It is a pocket guide to assist daily practice, describing
drug metabolism, excretion, and toxicity; which drugs can be
used in each week or month of the patient’s life; dose adjust-
ments; protocols; and other important details. The focus of
this book is safe treatment of children under 1 year old. It will
be essential to pediatric oncology/hematology institutions
and will be also very helpful to researchers, as it details the
metabolism of chemotherapy in these patients.
Curitiba, Paraná, Brazil
Carolina Witchmichen Penteado Schmidt
Contents
1 Introduction ....................................... 1
1.1 Concepts ................................. 1
1.2 D ifferences of Drug Metabolism in Neonates
and in Infants ............................. 2
1.3 C hemotherapy in Neonates and Infants....... 3
1.4 S tatistics on Diseases in Neonates
and Infants. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.5 Concepts of Oncohematology Treatment
of Neonates and Infants .................... 7
1.5.1 Congenital Tumors ................... 7
1.5.2 Teratomas........................... 8
1.5.3 Neuroblastoma ...................... 9
1.5.4 Central Nervous System Tumors ....... 10
1.5.5 Leukemias .......................... 11
1.5.6 Renal Tumors ....................... 12
1.5.7 Hepatic Tumors...................... 13
1.5.8 Other Tumors ....................... 14
2 Protocols Used in Chemotherapy Treatment
of Neonates and Infants ........................... 17
2.1 Acute Lymphoblastic Leukemia/Biphenotypic
Leukemia................................. 18
2.1.1 I nterfant-06 Protocol for Infants
Younger than 1 Year with Acute
Lymphoblastic Leukemia or Biphenotypic
Leukemia................................ 18
2.1.2 BFM95 (Berlin–Frankfurt–Münster)
Protocol for Children Under 1 Year Old
with Acute Lymphoid Leukemia ....... 41
viii Contents
2.2 Acute Myeloid Leukemia................... 56
2.2.1 AIEOP 2002/01 Protocol for Children
Under 1 Year Old with Acute Myeloid
Leukemia........................... 56
2.3 Central Nervous System .................... 63
2.3.1 CCG-9921 Protocol for Children
Younger than 36 Months with
Malignant Brain Tumor,
Medulloblastoma, Supratentorial
Primitive Neuroectodermal Tumor,
Ependymoma, or Rhabdoid Tumor ..... 63
2.4 Wilms’ Tumor ............................. 66
2.4.1 Protocol with Vincristine Used
as a Single Agent in a 3-Week-Old
Neonate ............................ 66
2.5 Hepatoblastoma........................... 68
2.5.1 Protocol with Cisplatin Used
as a Single Agent in a 2-Week-Old
Neonate ............................ 68
2.6 Retinoblastoma............................ 70
2.6.1 Guideline for Retinoblastoma
Treatment of Preterm and Full-Term
Neonates up to 3 Weeks Old, Including
Carboplatin ......................... 70
2.7 Neuroblastoma............................ 76
2.7.1 Case of a Neonate (Gestational
Age 40 Weeks) Diagnosed at 3 Days
of Age with Low-Risk Localized
Unresectable Neuroblastoma .......... 76
3 Pharmacokinetics and Pharmacodynamics
of Chemotherapy Drugs in Neonates and Infants ... 77
3.1 Pharmacokinetics of Chemotherapy
Drugs in Neonates and Infants............... 77
3.1.1 Absorption of Chemotherapy
in Neonates and Infants............... 78
3.1.2 Excretion of Chemotherapy
in Neonates and Infants............... 82
Contents ix
3.1.3 Drug Binding and Distribution
by Proteins in Neonates and Infants .... 83
3.1.4 Biotransformation by Enzyme
Complexes and Phase I and II
Reactions........................... 94
3.1.5 Enzymes That Metabolize
Chemotherapy....................... 97
3.1.6 Phase I and Phase II Reactions
in Neonates and Infants............... 97
3.1.7 Drug Excretion via the Renal
Route in Neonates and Infants......... 100
3.1.8 Excretion of Drugs via Other Paths
in Neonates and Infants............... 102
3.1.9 Repeated Administration of Drugs
and Notions of Pharmacokinetics
That Alter Chemotherapy
in Neonates and Infants............... 103
3.2 P harmacodynamics of Chemotherapy Drugs
in Neonates and Infants..................... 104
3.2.1 Dose–Response Relationship
and Therapeutic Index in Neonates
and Infants.......................... 105
4 Peculiarities of Most Commonly Used
Chemotherapy Drugs in Neonates and Infants . . . . . 107
4.1 6-Mercaptorurine.......................... 107
4.2 6-Tioguanine.............................. 108
4.3 Carboplatin............................... 109
4.4 Cisplatin..................................110
4.5 Cyclophosphamide......................... 111
4.6 Cytarabine................................111
4.7 Doxorubicin ..............................112
4.8 Etoposide.................................112
4.9 Methotrexate.............................. 113
4.10 Vincristine................................114
x Contents
5 Adjuvant Drugs Used in Chemotherapy for
Neonates and Infants . . . . . . . . . . . . . . . . . . . . . . . . . 115
5.1 Pain Management.......................... 115
5.1.1 Codeine ............................115
5.1.2 Morphine........................... 115
5.2 Nausea/Vomiting Management ..............123
6 Drug Interactions in Neonates and Infants ..........125
6.1 Human Milk Interactions
with Chemotherapy . . . . . . . . . . . . . . . . . . . . . . . . 125
6.2 D rug Interactions by Binding and Transport
Proteins in Neonates and Infants............. 126
6.3 D rug Interactions Involving Steroidal Anti-
inflammatories Commonly Used in Neonates
and Infants................................130
6.4 D rug Interactions Involving Antiemetic Drugs
Commonly Used in Neonates and Infants .....132
6.5 D rug Interactions with Chemotherapy
and Antibiotics Used in Neonates
and Infants................................132
6.5.1 Antibiotics and Platinum Compounds...132
6.5.2 Macrolide Antibiotics................. 133
6.5.3 Antibiotics Derived from Penicillin.....134
6.5.4 Sulfamethoxazole/Trimethoprim .......134
6.5.5 Antibiotics for Tuberculosis............ 134
6.6 D rug Interactions with Chemotherapy
and Antifungals Used in Neonates
and Infants................................135
6.7 P ain Management and Drug Interactions......136
7 Toxicity ...........................................137
7.1 Excipients of Drugs ........................ 137
7.2 Analgesics ................................142
7.2.1 Narcotics ...........................142
7.2.2 Genetics and Toxicity................. 143
7.3 T oxicity and Renal Excretion................ 146
Contents xi
8 Tumor Lysis in Neonates and Infants ...............147
9 Chemotherapy in Neonates and Infants with Cancer
and Other Congenital Diseases: Down Syndrome
and HIV ........................................... 151
9.1 Down Syndrome........................... 151
9.2 HIV .....................................154
10 Stem Cell Transplantation in Neonates
and Infants ........................................ 157
10.1 S tem Cell Transplantation in Patients Treated
with the Interfant-06 Protocol ...............159
10.1.1 Criteria............................. 159
10.1.2 Time of Scheduling................... 159
10.1.3 Human Leukocyte Antigen Typing
of the Patient and Donor, and Its
Priority in Transplantation............. 159
10.1.4 Stem Cell Source: Technical Choices .... 161
10.1.5 Conditioning Therapy for Stem Cell
Transplantation in Patients Treated
with the Interfant-06 Protocol.......... 161
Appendix ............................................. 167
References ............................................ 169
Index ................................................. 177