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Wilms Tumor Medication

  • Author: Arnold C Paulino, MD; Chief Editor: Jennifer Reikes Willert, MD  more...
 
Updated: Apr 27, 2016
 

Medication Summary

As previously stated, several cytotoxic agents may cause liver damage in patients treated for Wilms tumor. Reports have documented hepatic toxicity with the combination of vincristine and dactinomycin even in the absence of radiation therapy (which many early reports suggested was the major etiologic factor in liver damage).

In the fourth NWTSG report, the incidence of hepatotoxicity was 2.8-14.3% in patients who did not receive irradiation. The fact that patients who received less dactinomycin than others (ie, those with relatively low-stage disease) had a low incidence of 2.8% suggests a dose-related toxicity for dactinomycin.

Patients who survive Wilms tumor are at risk because inherited disposition and treatment (eg, chemotherapy, irradiation) can induce second malignant neoplasms. Although most secondary malignant neoplasms reported (eg, bone tumors, breast and thyroid cancers) have occurred in irradiated areas, certain chemotherapeutic agents, including doxorubicin, dactinomycin, and vincristine, may contribute to an increased risk for secondary malignancies.

A study by Pritchard-Jones et al on 583 children from 251 hospitals in 26 countries aimed to assess whether doxorubicin can be omitted safely from chemotherapy for stage II-III, histological intermediate-risk Wilms' tumor in order to avoid doxorubicin-related cardiotoxicity effects. The study concluded that doxorubicin does not need to be included in treatment of stage II-III intermediate risk Wilms' tumour when the histological response to preoperative chemotherapy is incorporated into the risk stratification.[36, 37, 38]

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Antineoplastic agents

Class Summary

These chemotherapeutic agents used to treat patients with Wilms tumor depend on the stage and histology of disease. Commonly used agents include dactinomycin, vincristine, doxorubicin, cyclophosphamide, etoposide, and carboplatin. The dosage depends on the particular stage of the disease and on the child.

Dactinomycin (Cosmegen)

 

This antibiotic is derived from Streptomyces bacterium. It binds to the guanine portion of deoxyribonucleic acid (DNA) and causes topoisomerase-mediated breaks in DNA strands.

Vincristine (Vincasar PFS)

 

Vincristine inhibits tubulin polymerization; therefore, it targets dividing cells.

Cyclophosphamide

 

This alkylating agent is believed to be cytotoxic to dividing cells through cross-linkage of cellular DNA. It is processed in the liver to active metabolites; byproducts (eg, acrolein) accumulate in the bladder and cause cystitis.

Etoposide (Toposar)

 

Etoposide inhibits topoisomerase II; therefore, it is toxic to cells undergoing DNA replication.

Carboplatin

 

This analog of cisplatin is used in treatment regimens for relapse.

Doxorubicin (Adriamycin)

 

Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius (var caesius). It binds to nucleic acids, presumably by the specific intercalation of the anthracycline nucleus with the DNA double helix

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Contributor Information and Disclosures
Author

Arnold C Paulino, MD Professor of Radiation Oncology, Methodist Hospital and Weill-Cornell Medical College; Associate Professor of Pediatrics, Baylor College of Medicine

Arnold C Paulino, MD is a member of the following medical societies: Radiological Society of North America, Children's Oncology Group, American Society of Clinical Oncology, International Society of Paediatric Oncology, American Medical Association, American Radium Society, American Society for Radiation Oncology

Disclosure: Received royalty from Elsevier, Inc for author of book.

Coauthor(s)

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Jennifer Reikes Willert, MD Associate Clinical Professor, Department of Pediatrics, Division of Pediatric Hematology/Oncology, Section of Stem Cell Transplantation, Stanford University Medical Center, Lucile Packard Children's Hospital

Jennifer Reikes Willert, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Hematology, American Society for Blood and Marrow Transplantation, Children's Oncology Group, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Additional Contributors

Kathleen M Sakamoto, MD, PhD Shelagh Galligan Professor, Division of Hematology/Oncology, Department of Pediatrics, Stanford University School of Medicine

Kathleen M Sakamoto, MD, PhD is a member of the following medical societies: International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

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CT scan in a patient with a right-sided Wilms tumor with favorable histology.
CT scan of child with a stage IV Wilms tumor with favorable histology. Note the bilateral pulmonary metastases.
Gross nephrectomy specimen shows a Wilms tumor pushing the normal renal parenchyma to the side.
Table 3. Survival Rates in Patients with Favorable-Histology Wilms Tumor
Stage Relapse-Free Survival, % Overall Survival, %
I 92 98
II 85 96
III 90 95
IV 80 90
Table 1. Current Approach to Favorable Histology Wilms Tumor by Stage
Stage and Histology Surgery Chemotherapy Radiation Therapy*
Stage I or II favorable histology without loss of heterozygosity (LOH) 1p and 16q† Nephrectomy Vincristine, dactinomycin No
Stage I or II favorable histology with LOH 1p and 16q Nephrectomy Vincristine, dactinomycin, doxorubicin No
Stage III and IV favorable histology without LOH 1p and 16q Nephrectomy Vincristine, dactinomycin, doxorubicin Yes
Stage III and IV favorable histology with LOH 1p and 16q Nephrectomy Vincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposide Yes
* The current dose for radiation therapy for favorable histology Wilms tumor is approximately 1080 cGy for the abdomen and 1200 cGy for the lung.[28] Postoperative radiotherapy is started within 14 days of nephrectomy.[29] Patients with stage IV favorable histology Wilms tumor and lung metastases whose pulmonary lesions do not disappear after 6 weeks of chemotherapy receive whole-lung radiation therapy.



† Some evidence suggests that certain children with stage I disease and favorable histology do well with nephrectomy alone.[30] Children younger than 24 months with small (< 550 g) Wilms tumors with favorable histology are noted in the current COG protocol.



Table 2. Recommended Follow-Up Imaging Studies in Children with Wilms Tumor Without Metastasis at Diagnosis *
Stage and Type of Wilms Tumor Imaging Studies Off-Treatment Schedule
Stages I, II, and III with favorable histology; stages I, II, and III with anaplastic histology Chest radiography 6 wk and 3 mo after surgery, then every 3 mo (5 times), then every 6 mo (3 times), then yearly (2 times)
All stages in patients aged < 48 mo at diagnosis with nephrogenic rests Abdominal ultrasonography Every 3 mo for 6 y
All stages in patients aged >48 mo at diagnosis with nephrogenic rests Abdominal ultrasonography Every 3 mo for 4 y
Stages I and II with favorable histology Abdominal ultrasonography Yearly (6 times)
Stage III with favorable histology Abdominal ultrasonography 6 wk and 3 mo after surgery, then every 3 mo (5 times), then every 6 mo (3 times), then yearly (2 times)
All stages with unfavorable histology Abdominal ultrasonography Every 3 mo (4 times), then every 6 mo (4 times)
* Subsequent imaging studies should be performed as clinically indicated.
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