Wilms Tumor Medication

  • Author: Arnold C Paulino, MD; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: Sep 23, 2011
 

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.

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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.

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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.

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Vincristine (Vincasar PFS)

 

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

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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.

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Etoposide (Toposar)

 

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

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Carboplatin

 

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

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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: American Medical Association, American Radium Society, American Society for Therapeutic Radiology and Oncology, American Society of Clinical Oncology, Children's Oncology Group, International Society of Paediatric Oncology, and Radiological Society of North America

Disclosure: Nothing to disclose.

Coauthor(s)

Max J Coppes, MD, PhD, MBA  Senior Vice President, Center for Cancer and Blood Disorders, Children's National Medical Center; Professor of Medicine, Oncology, and Pediatrics, Georgetown University School of Medicine; Clinical Professor of Pediatrics, George Washington University School of Medicine and Health Sciences

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

Disclosure: Nothing to disclose.

Specialty Editor Board

Kathleen M Sakamoto, MD, PhD  Professor and Chief, Division of Hematology-Oncology, Vice-Chair of Research, Mattel Children's Hospital at UCLA; Co-Associate Program Director of the Signal Transduction Program Area, Jonsson Comprehensive Cancer Center, California Nanosystems Institute and Molecular Biology Institute, University of California, Los Angeles, David Geffen School of Medicine

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

Disclosure: Nothing to disclose.

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, American Society of Clinical Oncology, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, and International Society for Experimental Hematology

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD  King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

References

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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
StageRelapse-Free Survival, %Overall Survival, %
I9298
II8596
III9095
IV8090
Table 1. Current Approach to Favorable Histology Wilms Tumor by Stage
Stage and HistologySurgeryChemotherapyRadiation Therapy*
Stage I or II favorable histology without loss of heterozygosity (LOH) 1p and 16q†NephrectomyVincristine, dactinomycinNo
Stage I or II favorable histology with LOH 1p and 16qNephrectomyVincristine, dactinomycin, doxorubicinNo
Stage III and IV favorable histology without LOH 1p and 16qNephrectomyVincristine, dactinomycin, doxorubicinYes
Stage III and IV favorable histology with LOH 1p and 16qNephrectomyVincristine, dactinomycin, doxorubicin, cyclophosphamide, etoposideYes
* The current dose for radiation therapy for favorable histology Wilms tumor is approximately 1080 cGy for the abdomen and 1200 cGy for the lung.[24] Postoperative radiotherapy is started within 14 days of nephrectomy.[25] 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.[26] 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 TumorImaging StudiesOff-Treatment Schedule
Stages I, II, and III with favorable histology; stages I, II, and III with anaplastic histologyChest radiography6 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 restsAbdominal ultrasonographyEvery 3 mo for 6 y
All stages in patients aged >48 mo at diagnosis with nephrogenic restsAbdominal ultrasonographyEvery 3 mo for 4 y
Stages I and II with favorable histologyAbdominal ultrasonographyYearly (6 times)
Stage III with favorable histologyAbdominal ultrasonography6 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 histologyAbdominal ultrasonographyEvery 3 mo (4 times), then every 6 mo (4 times)
* Subsequent imaging studies should be performed as clinically indicated.
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