Sections View Full Chapter Figures Tables Videos Full Chapter Figures Tables Videos Supplementary Content +++ 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 Graphic Jump LocationTABLE 21-1 Commonly Used Chemotherapy Agents and Important Agent-Specific Toxicities View Table||Download (.pdf) 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... Your MyAccess profile is currently affiliated with '[InstitutionA]' and is in the process of switching affiliations to '[InstitutionB]'. Please click ‘Continue’ to continue the affiliation switch, otherwise click ‘Cancel’ to cancel signing in. Get Free Access Through Your Institution Learn how to see if your library subscribes to McGraw Hill Medical products. Subscribe: Institutional or Individual Sign In Username Error: Please enter User Name Password Error: Please enter Password Forgot Username? Forgot Password? Sign in via OpenAthens Sign in via Shibboleth