Sections View Full Chapter Figures Tables Videos Annotate Full Chapter Figures Tables Videos Supplementary Content +++ 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 Graphic Jump LocationTable 22-1Commonly Used Chemotherapy Agents and Important Agent-Specific ToxicitiesView Table||Download (.pdf) Table 22-1 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) Neurotoxicity (ifosfamide) Infertility Hydration Mesna Methylene blue (for ifosfamide neurotoxicity) Cisplatin Carboplatin Platinums Plastination/cross-linking Ototoxicity Nephrotoxicity (↓CrCl and electrolyte wasting) Infertility Hydration and electrolyte replacement Audiogram before each cycle to assess if dose reduction required Doxorubicin, daunorubicin, mitoxantrone, idarubicin Anthracyclines DNA intercalation Cardiac (cardiomyopathy and arrhythmia) Mucositis Dexrazoxane (cardioprotectant) Vincristine, vinblastine Vinca alkaloids Inhibition of microtubule spindle formation Constipation Peripheral neuropathy SIADH Bowel regimen Decreased dose if necessary Methotrexate Antimetabolites DNA precursor analogues Nephrotoxicity, hepatotoxicity Neurotoxicity (highest risk with intrathecal) Hydration, urine alkalization, and leucovorin for high dose If nephrotoxicity develops, consider glucarpidase 6-Mercaptopurine Thioguanine Antimetabolites DNA precursor analogues Hepatotoxicity Veno-occlusive disease (thioguanine) Thiopurine methyltransferase 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 Consider premedication due to frequent anaphylaxis Imatinib Sorafenib Tyrosine kinase inhibitors Inhibit certain tyrosine kinases Hypertension Rash Esophagitis/gastritis Switching to another agent in same class Take medication with lots of fluids SIADH = syndrome of inappropriate antidiuretic hormone. +++ 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... Your Access profile is currently affiliated with [InstitutionA] and is in the process of switching affiliations to [InstitutionB]. Please select how you would like to proceed. Keep the current affiliation with [InstitutionA] and continue with the Access profile sign in process Switch affiliation to [InstitutionB] and continue with the Access profile sign in process 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 Error: Incorrect UserName or Password Username Error: Please enter User Name Password Error: Please enter Password Sign in Forgot Password? Forgot Username? Sign in via OpenAthens Sign in via Shibboleth You already have access! Please proceed to your institution's subscription. Create a free profile for additional features.