Medication Summary
As previously mentioned, treatment of Ewing sarcoma lasts 6-9 months and consists of alternating courses of 2 chemotherapeutic regimens: (1) vincristine, doxorubicin, and cyclophosphamide and (2) ifosfamide and etoposide. [4]
Dose intensity is critical in the treatment of these tumors. To facilitate maximum dosing of chemotherapeutic agents, anticipatory supportive care is necessary. Neutrophils are stimulated with G-CSF, and fevers are aggressively treated. New symptoms that occur while patients are being treated should be closely evaluated and monitored.
Antineoplastic Agents
Class Summary
Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect it. After cells divide, they enter a period of growth (G1 phase), followed by DNA synthesis (S phase). The next phase is a premitotic phase (G2 phase), after which comes the final phase, mitotic cell division (M phase).
Rates of cell division vary for different tumors. Most common cancers grow slowly compared with normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant ones do. This is partly the rationale for current cyclic dosage schedules.
Antineoplastic agents interfere with cellular reproduction. Some agents are specific to the cell cycle, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not. Cellular apoptosis (programmed cell death) is also a potential mechanism of many antineoplastic agents.
Doxorubicin (Adriamycin)
Multiple mechanisms of action are recognized for doxorubicin (eg, DNA intercalation, topoisomerase-mediated DNA strand breaks, oxidative damage by free radical production).
Cyclophosphamide
This agent exerts its cytotoxic effect through alkylation of DNA, which leads to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA replication.
Vincristine (Vincasar PFS)
Vincristine is a plant-derived vinca alkaloid that acts as mitotic inhibitor by binding tubulin. It inhibits microtubule formation in the mitotic spindle, causing metaphase arrest.
Ifosfamide (Ifex)
Ifosfamide exerts its cytotoxic effect via alkylation of DNA, leading to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA replication.
Etoposide (Toposar)
Etoposide is a glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect by stabilizing normally transient covalent intermediates formed between DNA substrate and topoisomerase II. This results in single- and double-strand DNA breaks.
Uroprotectants
Class Summary
Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide or cyclophosphamide. In the kidney, mesna disulfide is reduced to free mesna. Free mesna has thiol groups that react with acrolein, the ifosfamide and cyclophosphamide metabolite considered responsible for urotoxicity.
Mesna (Mesnex)
Mesna inactivates acrolein (the urotoxic metabolite of ifosfamide and cyclophosphamide) and prevents urothelial toxicity without affecting cytostatic activity.
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Radiograph of an 11-year-old boy with a large Ewing sarcoma in the right pelvic area. Destruction of the bone structure resulted from tumor involvement.
