Medication Summary
The role of chemotherapy in the treatment of ependymoma has not been established.
Numerous drugs have been identified with activity against ependymoma in single-agent chemotherapy regimens in phase II trials. Of these, platinum compounds have been the most active (eg, cisplatin is the most effective single agent, with a 30% response rate).
Despite these findings, combination chemotherapeutic regimens for ependymoma have yielded disappointing results. The most encouraging data have been reported in infants using postoperative therapy consisting of cisplatin, cyclophosphamide, etoposide, and vincristine, with deferred radiation (2-y survival rate of 74%).
Current trials are evaluating the benefits of this regimen in older children with postoperative residual disease. At present, no definitive conclusions can be drawn.
An example of the dosing and administration of preirradiation chemotherapeutic agents used in a recent investigational protocol for children older than 3 years with postoperative residual disease is provided below. [16]
Antineoplastic agents
Class Summary
These agents disrupt DNA replication, which inhibits tumor growth and promotes tumor cell death. Cancer chemotherapy is based on an understanding of tumor cell growth and how drugs affect this growth. After cells divide, they enter a period of growth (phase G1), followed by DNA synthesis (phase S). The next phase is a premitotic phase (G2), then finally a mitotic cell division (phase M).
The cell division rate varies for different tumors. Most common cancers increase very slowly in size compared to normal tissues, and the rate may decrease further in large tumors. This difference allows normal cells to recover more quickly than malignant ones from chemotherapy and is the rationale behind current cyclic dosage schedules.
Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not phase-specific. Cellular apoptosis (ie, programmed cell death) is also a potential mechanism of many antineoplastic agents.
Vincristine (Oncovin)
Plant-derived vinca alkaloid. Acts as a mitotic inhibitor by binding tubulin. Inhibits microtubule formation in the mitotic spindle, causing metaphase arrest.
Cisplatin (Platinol)
Heavy metal coordination complex that exerts its cytotoxic effect by platination of DNA, a mechanism analogous to alkylation. This leads to interstrand and intrastrand DNA crosslinks and inhibition of DNA replication.
Cyclophosphamide (Cytoxan)
Exerts its cytotoxic effect by alkylation of DNA, leading to interstrand and intrastrand DNA crosslinks, DNA-protein crosslinks, and inhibition of DNA replication.
Etoposide (VePesid, VP-16)
Glycosidic derivative of podophyllotoxin that exerts its cytotoxic effect through stabilization of the normally transient covalent intermediates formed between DNA substrate and topoisomerase II, leading to single-stand and double-strand DNA breaks.
Antidote, cyclophosphamide-induced hemorrhagic cystitis
Class Summary
This agent is a detoxifying agent used as a protectant against hemorrhagic cystitis induced by cyclophosphamide.
Mesna (Mesnex)
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. Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.
Colony-stimulating factors
Class Summary
These agents reduce the duration of neutropenia and the associated risk of infection in patients receiving myelosuppressive chemotherapy. They act as a hematopoietic growth factor that stimulates the development of granulocytes. They are used to treat or prevent neutropenia when receiving myelosuppressive cancer chemotherapy and to reduce the period of neutropenia associated with bone marrow transplantation. These agents are also used to mobilize autologous peripheral blood progenitor cells for bone marrow transplantation and in the management of chronic neutropenia.
Filgrastim (Neupogen, G-CSF)
Granulocyte colony-stimulating factor that activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils.
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MRI showing an ependymoma of the fourth ventricle, compressing the cerebellum and brain stem.
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Sagittal section of an ependymoma of the fourth ventricle.
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Section displaying typical perivascular pseudorosettes of a benign ependymoma.
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Section displaying high cellularity, nuclear atypia, and numerous mitoses characteristic of an anaplastic ependymoma.
