Pediatric Adrenal Carcinoma Medication

  • Author: Lawrence C Wolfe, MD; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: Nov 22, 2011
 

Medication Summary

Adjuvant or palliative treatment has been studied by using mitotane, cisplatin, etoposide, and doxorubicin. Mitotane leads to autodestruction of the adrenal cortex. Therefore, it is used in almost all protocols in the hope that it will decrease any autonomous hormone production and suppress tumor growth. Chemotherapy has focused on 3 antineoplastics given alone or in combination: cisplatin, etoposide, and doxorubicin. Studies have focused on etoposide and cisplatin or etoposide, doxorubicin, and cisplatin.

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Antineoplastic agents

Class Summary

Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (phase G2). Finally, a period of mitotic cell division (phase M) occurs.

Rates of cell division vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the rate may decrease if tumors are large. This difference allows healthy cells to recover from chemotherapy more quickly than do malignant cells, and this is the rationale for current cyclic dosage schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are specific to certain phases of the cell cycle, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase specific. Cellular apoptosis (ie, programmed cell death) is another potential mechanism of many antineoplastic agents.

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Mitotane (Lysodren)

 

Decreases production of cortisol by causing adrenal atrophy and affecting mitochondria in adrenocortical cells. No pediatric standards or dosages established, and doses in children must be individualized.

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Cisplatin (Platinol)

 

Inhibits DNA synthesis and, therefore, cell proliferation by causing DNA crosslinking and denaturation of double helix.

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Doxorubicin (Adriamycin)

 

Cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius. Blocks DNA and RNA synthesis by inserting between adjacent base pairs and binding to sugar-phosphate backbone of DNA, inhibiting DNA polymerase. Binds to nucleic acids presumably by specific intercalation of anthracycline nucleus with DNA double helix. Can also cause DNA strand breakage because of effects on topoisomerase II.

Powerful iron chelator. Iron-doxorubicin complex induces production of free radicals that can destroy DNA and cancer cells.

Maximum toxicity during S phase of cell cycle.

Has multiphasic disappearance curve, with half-lives up to 30 h. Does not cross blood-brain barrier but taken up rapidly by heart, lungs, liver, kidney, and spleen.

Both mutagenic and carcinogenic. Dosage related to body surface area.

Antiproliferative drugs may be useful for patients with diffuse metastases to palliate symptoms.

Liposomes in different drug products can vary in chemical and physical properties, which can substantially affect functional properties.

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Etoposide (Toposar, VePesid)

 

Glycosidic derivative of podophyllotoxin that exerts cytotoxic effect by stabilizing normally transient covalent intermediates formed between DNA substrate and topoisomerase II. Leads to single-strand and double-strand DNA breaks that arrest cellular proliferation in late S or early G2 phase of cell cycle.

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Contributor Information and Disclosures
Author

Lawrence C Wolfe, MD  Senior Associate in Pediatric Hematology/Oncology, Schneider Children's Hospital

Lawrence C Wolfe, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Association of Blood Banks, American Society of Hematology, Children's Oncology Group, and Eastern Society for Pediatric Research

Disclosure: Nothing to disclose.

Specialty Editor Board

Samuel Gross, MD  Professor Emeritus, Department of Pediatrics, University of Florida; Clinical Professor, Department of Pediatrics, University of North Carolina; Adjunct Professor, Department of Pediatrics, Duke University

Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and 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.

Timothy P Cripe, MD, PhD  Professor of Pediatrics, Division of Hematology/Oncology, Cincinnati Children's Hospital Medical Center; Clinical Director, Musculoskeletal Tumor Program, Co-Medical Director, Office for Clinical and Translational Research, Cincinnati Children's Hospital Medical Center; Director of Pilot and Collaborative Clinical and Translational Studies Core, Center for Clinical and Translational Science and Training, University of Cincinnati College of Medicine

Timothy P Cripe, MD, PhD is a member of the following medical societies: American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, American Society of Pediatric Hematology/Oncology, and Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary E Cataletto, MD  Director of Children's Sleep Services, Winthrop Sleep Disorders Center, Mineola, NY; Professor of Clinical Pediatrics, State University of New York at Stony Brook, Stony Brook, NY

Mary E Cataletto, MD is a member of the following medical societies: American Academy of Pediatrics and American College of Chest Physicians

Disclosure: Shering Plough Pharmaceuticals Honoraria Consulting

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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