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CHEMOTHERAPY

General Principles

  • Cancer cells divide rapidly and are, 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 because most malignancies have a steep dose–response curve

    • ✓ The main approaches are to either increase dose (per cycle or by increasing the total number of chemotherapy cycles) or to decrease the interval between treatment cycles.

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

    • ✓ Targeted at micrometastases (see “Solid Tumor” section)

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

    • ✓ There are also many long-term toxicities (see “Late Effects of Cancer Treatment” section).

    • ✓ See Table 22-1 for specific toxicities relevant to commonly used agents in pediatric oncology.

Table 22-1Commonly Used Chemotherapy Agents and Important Agent-Specific Toxicities

RADIATION THERAPY

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

    ...

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