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CHAPTER 21: Oncology

Jason L. Freedman; Benjamin R. Oshrine; Naomi Balamuth

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    AMA Citation
    Freedman JL, Oshrine BR, Balamuth N. Freedman J.L., Oshrine B.R., Balamuth N Freedman, Jason L., et al.Oncology. In: Shah SS, Zaoutis LB, Catallozzi M, Frank G. Shah S.S., Zaoutis L.B., Catallozzi M, Frank G Eds. Samir S. Shah, et al.eds. The Philadelphia Guide: Inpatient Pediatrics, 2e New York, NY: McGraw-Hill; . http://accesspediatrics.mhmedical.com/content.aspx?bookid=1698&sectionid=112041916. Accessed January 17, 2019.
    MLA Citation
    Freedman JL, Oshrine BR, Balamuth N. Freedman J.L., Oshrine B.R., Balamuth N Freedman, Jason L., et al.. "Oncology." The Philadelphia Guide: Inpatient Pediatrics, 2e Shah SS, Zaoutis LB, Catallozzi M, Frank G. Shah S.S., Zaoutis L.B., Catallozzi M, Frank G Eds. Samir S. Shah, et al. New York, NY: McGraw-Hill, , http://accesspediatrics.mhmedical.com/content.aspx?bookid=1698&sectionid=112041916.

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PRINCIPLES OF TREATING CANCER

CHEMOTHERAPY

GENERAL PRINCIPLES

  • Cancer cells are rapidly dividing, and therefore more susceptible to cytotoxic agents

  • Combination therapy is useful for preventing the development of resistance and overcoming existing resistance by using agents with different mechanisms of action

    • ✓ Also permits more intensive overall therapy by using agents with nonoverlapping toxicities

  • Dose-intensification effective as most malignancies have a steep dose-response curve

    • ✓ Two main approaches: Increase dose (per cycle or by increasing the total number of chemotherapy cycles) or decrease interval between treatment cycles

    • ✓ Increases supportive care requirements

  • Adjuvant therapy: Administration of systemic chemotherapy in the absence of overt disease

    • ✓ Targeted at micrometastases (see Solid Tumor section)

  • Toxicities: Myelosuppression, alopecia, nausea/vomiting are most common acute toxicities (see Principles of Supportive Care for management of specific toxicities)

    • ✓ Long-term many agents affect fertility and can cause secondary leukemia

    • ✓ See Table 21-1 for specific toxicities relevant to commonly used agents in pediatric oncology

TABLE 21-1

Commonly Used Chemotherapy Agents and Important Agent-Specific Toxicities

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TABLE 21-1

Commonly Used Chemotherapy Agents and Important Agent-Specific Toxicities
Agent(s) Class Mechanism of Action Specific Toxicities Prevention/Treatment

Cyclophosphamide

Ifosfamide

 Alkylators DNA cross-linking

Hemorrhagic cystitis

Fanconi syndrome (Ifosfamide)

Hydration

Mesna

Cisplatin

Carboplatin

 Platinum Platination/Cross-linking

Ototoxicity

Nephrotoxicity (↓Cr and electrolyte wasting)

 Hydration and electrolyte replacement
Doxorubicin, daunorubicin, mitoxantrone, idarubicin Anthracycline DNA intercalation

Cardiac (cardiomyopathy and arrhythmia)

Mucositis

 Dexrazoxane (cardioprotectant)
Vincristine, Vinblastine Vinca alkaloids Inhibition of microtubule spindle formation

Constipation

Peripheral neuropathy

Bowel regimens

Decreased dose if necessary
Methotrexate Antimetabolites DNA precursor analogues Nephrotoxicity, hepatotoxicity Hydration, urine alkalization, and leucovorin for high dose

6-Mercaptopurine

Thioguanine

 Hepatotoxicity TPMT genotyping for slow metabolizers to dose correctly
Etoposide Epipodophyllotoxin Topoisomerase inhibitor

Hypotension

Anaphylaxis

 Slow the infusion rate if hypotension
Asparaginase Enzyme Asparagine depletion

Pancreatitis

Thrombosis

Anaphylaxis

 Can switch to another type/hypoallergenic form

Imatinib

Sorafenib

 Tyrosine kinase inhibitors Inhibit certain tyrosine kinases

Hypertension

Rash

 Switching to another agent in same class

RADIATION THERAPY (RT)

GENERAL PRINCIPLES

  • Delivery of ionizing radiation typically by external beam

  • Biologic effect achieved by inducing direct and indirect DNA damage

  • Different tumor types have different required doses for efficacy

    • ✓ Wide range (e.g., 21 Gy for neuroblastoma/lymphoma, up to 60+Gy for sarcomas)

  • Normal tissues have different dose tolerance thresholds before toxicity is seen

  • Effect (and toxicity) can be potentiated by concomitant chemotherapy (e.g., doxorubicin, dactinomycin)

  • Radiation recall: Inflammation in previous radiation field after administration of certain chemotherapy (days to years after original treatment)

  • Photons versus protons

    • ✓ Photons are standard, but deliver radiation to all structures in path (i.e., entry and exit doses)

      • ▪ Intensity-modulated RT (IMRT) is used to carve out treatment volume to minimize exposure to normal tissues

    • ✓ Protons are heavier and deposit radiation more precisely at target

      • ▪ Decreased exposure to normal tissues as they enter/exit target areas

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