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PRINCIPLES OF TREATING CANCER

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CHEMOTHERAPY

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GENERAL PRINCIPLES

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  • 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

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TABLE 21-1

Commonly Used Chemotherapy Agents and Important Agent-Specific Toxicities

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RADIATION THERAPY (RT)

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GENERAL PRINCIPLES

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  • 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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