Pediatric Teratomas and Other Germ Cell Tumors Medication

Updated: Jul 31, 2019
  • Author: E Stanton Adkins, III, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Medication

Medication Summary

Since the introduction of platinum-based therapy for this disease, the survival rate has improved considerably. First-line therapy includes the use of bleomycin, etoposide, and cisplatin (BEP). Survival with carboplatin-containing regimens has not been as favorable. For low-risk tumors (testicular stage II; ovarian stage I and II), four cycles of BEP has a survival rate of 94-100%. For high-risk tumors (testicular and ovarian stage III and IV; extragonadal stage I-IV), high-dose BEP has better overall survival at the cost of some increase in toxicity.

Salvage therapy typically consists of a combination of paclitaxel, ifosfamide, carboplatin, etoposide, and vinblastine or vincristine plus peripheral blood stem cell (PBSC) transplantation. Gemcitabine has been used as salvage therapy in a phase 2 protocol.

Kollmannsberger et al reported improved 2-year survival with a second course of high-dose chemotherapy with stem cell rescue and complete surgical resection in high-risk patients who failed initial ablative chemotherapy and autologous stem cell transplant. [46]

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Antineoplastic agents

Class Summary

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 (ie, phase G1), followed by DNA synthesis (ie, phase S). The next phase is a premitotic phase (ie, G2). Finally, a mitotic cell division occurs (ie, phase M). Cell division rates vary for different tumors.

Antineoplastic agents interfere with cell reproduction. Some agents are cell cycle specific, while 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.

Current protocols use these agents in combinations that exploit differences in growth and recovery between tumors and normal tissues.

Bleomycin (Blenoxane)

Glycopeptide antibiotic that inhibits DNA synthesis. For palliation in the management of several neoplasms.

Etoposide (Toposar, VePesid)

Inhibits topoisomerase II and causes DNA strand breakage, which arrests cell proliferation in the late S or early G2 portion of the cell cycle.

Vinblastine (Velban)

Inhibits microtubule formation, which, in turn, disrupts the formation of the mitotic spindle, causing cell proliferation to arrest at metaphase.

Cisplatin (Platinol)

Inhibits DNA synthesis and, thus, cell proliferation by causing DNA cross-linking and denaturation of the double helix.

Carboplatin (Paraplatin)

Analog of cisplatin. Has same efficacy as cisplatin but with a better toxicity profile. Dose is based on the following formula: total dose (mg) = (target AUC) X (GFR + 25), where AUC is the area under plasma concentration-time curve expressed in mg/mL/min, and GFR is expressed in mL/min.

Paclitaxel (Taxol)

Mechanisms of action are tubulin polymerization and microtubule stabilization.

Ifosfamide (Ifex)

Inhibits DNA and protein synthesis and, thus, cell proliferation by causing DNA cross-linking and denaturation of the double helix.

Gemcitabine (Gemzar)

Cytidine analog. After it is intracellularly metabolized to become an active nucleotide, it inhibits ribonucleotide reductase and competes with deoxycytidine triphosphate for incorporation into DNA.

This drug has been shown to have activity in a phase 2 trial against relapsed germ cell tumors.

Vincristine (Vincasar PFS, Oncovin)

Mechanism of action is uncertain. May involve a decrease in reticuloendothelial cell function or an increase in platelet production. However, neither of these mechanisms fully explains the effect in TTP and HUS.

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Antibiotic agents

Class Summary

Trimethoprim and sulfamethoxazole (TMP-SMZ) is indicated for prophylaxis of Pneumocystis carinii infection.

Trimethoprim and sulfamethoxazole (Septra, Bactrim)

Dihydrofolate reductase inhibitor that prevents tetrahydrofolic acid production in bacteria. Active in vitro against a broad range of gram-positive and gram-negative bacteria, including uropathogens (eg, Enterobacteriaceae species, Staphylococcus saprophyticus). Resistance is usually mediated by decreased cell permeability or alterations in amount or structure of dihydrofolate reductase. Demonstrates synergy with sulfonamides, potentiating inhibition of bacterial tetrahydrofolate production.

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Uroprotective antidotes

Class Summary

Mesna is a prophylactic detoxifying agent used to inhibit hemorrhagic cystitis caused by ifosfamide and 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)

Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.

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Antiemetic agents

Class Summary

Antiemetics should be administered before, during, and for 6 hours after chemotherapy. Antineoplastic-induced vomiting is stimulated through the chemoreceptor trigger zone (CTZ), which then stimulates the vomiting center (VC) in the brain. Increased activity of the central neurotransmitters dopamine in CTZ or acetylcholine in VC appears to be a major mediator for inducing vomiting. After the administration of antineoplastic agents, serotonin (5-HT) is released from enterochromaffin cells in the GI tract. With serotonin release and subsequent binding to 5-HT3-receptors, vagal neurons are stimulated; they transmit signals to the VC, resulting in nausea and vomiting.

Antineoplastic agents may cause nausea and vomiting so intolerable that patients may refuse further treatment. Some antineoplastic agents are more emetogenic than others. Prophylaxis with antiemetic agents prior to and after cancer treatment is often essential to ensure administration of the entire chemotherapy regimen.

Ondansetron (Zofran)

Selective 5-HT3-receptor antagonist that blocks serotonin both peripherally and centrally. Prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and complete-body radiotherapy.

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