CHEMOTHERAPY tumors. For patients with localized solid tumors, chemo-Because most pediatric solid tumors have a high risk for therapy administered after removal of the primary tumor is micrometastatic disease at the time of diagnosis, chemo-referred to as adjuvant therapy. Chemotherapy administered therapy is used in almost all cases (Table 154-2). Exceptions while the primary tumor is still present is referred to as neoinclude low-stage neuroblastoma and Wilms tumor (particu-adjuvant chemotherapy. Neoadjuvant chemotherapy has larly in infants) and low-grade central nervous system (CNS) a number of potential benefits, including an early attack on
Methotrexate Folic acid Hepatic Renal, 50%–90% ALL, lymphoma, Myelosuppression (nadir 7–10 antagonist; inhibits excreted medulloblastoma, days), mucositis, dermatitis, dihydrofolate unchanged; biliary osteosarcoma hepatitis, renal and CNS reductase effects with high-dose administration; prevent with hydration and leucovorin, monitor levels 6-Mercaptopurine Purine analog Hepatic Renal ALL Myelosuppression; hepatitis; mucositis; allopurinol increases toxicity myopathy, osteoporosis, infection, peptic ulceration, irritability, psychosis, hunger, fluid retention
Chapter 154 u Principles of Cancer Treatment 541
Table 154-2 Cancer Chemotherapy—cont’d DRUG* ACTION METABOLISM EXCRETION INDICATION ACUTE TOXICITY Antimetabolites Hormones Prednisone Direct lymphocyte cytotoxicity Hepatic Renal ALL; Hodgkin disease, lymphoma Cushing syndrome, cataracts, diabetes, hypertension,
Carboplatin Inhibits DNA — Renal Same as for cisplatin Myelosuppression synthesis
Etoposide (VP-16) Topoisomerase-— Renal ALL, lymphoma, germ Myelosuppression, secondary inhibitor cell tumor, sarcoma leukemia, allergic reaction
ADH, Antidiuretic hormone; ALL, acute lymphoblastic leukemia; AML, acute myeloid leukemia; CNS, central nervous system. *Many drugs produce nausea and vomiting during administration, and many cause alopecia with repeated doses.
presumed micrometastatic disease, shrinkage of the primary tumor to facilitate local control, and additional time to plan for definitive surgery.
Resistance to a particular chemotherapeutic agent can develop in a number of ways: decreased influx into or increased efflux of the chemotherapeutic agent from the malignant cell; mutation in the target tissue so that it cannot be inhibited by the drug; amplification of a drug target to overcome inhibition; and blockade of normal cellular processes leading to programmed cell death or apoptosis. Because mutation is an ongoing process in malignant tumors, it follows that certain subpopulations of tumor cells within a tumor may be more or less sensitive to any particular chemotherapy drug. Given this fact, combinations of chemotherapy drugs are used, as opposed to sequential single agents, to treat the various forms of childhood cancer.
The blood-brain barrier prevents the penetration of chemotherapeutic drugs into the CNS; instillation of the chemotherapeutic agent directly into the cerebrospinal fluid (by lumbar puncture) may be necessary. Radiation therapy also circumvents the blood-brain barrier.
Radiation therapy is the process of delivering ionizing radiationto malignant cells in order to kill them directly or, more commonly, prevent them from dividing by interfering with DNAreplication. Conventional radiation therapy uses photons, butatomic particles such as electrons, protons, and neutrons canalso be used. Not all tumors are radiosensitive, and radiation therapy is not necessary in all tumors that are radiosensitive.