Nonrhabdomyosarcoma Soft Tissue Sarcomas Medication
- Author: Justine K Walker, MD; Chief Editor: Robert J Arceci, MD, PhD more...
Medication Summary
The chemotherapeutic agents described below are used in select cases of nonrhabdomyosarcoma soft tissue sarcoma (NRSTS). Dosages and schedules of treatment for individual agents vary with the clinical environment with the particular patient. For each agent, general facts, representative pediatric dosages, and toxicities are noted.
Chemotherapeutic 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), then finally a mitotic cell division (ie, 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 it is the rationale behind current cyclic dosage schedules.
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) also is a potential mechanism of many antineoplastic agents. Refer to specific protocol for duration of therapy with each drug and timing of administration within each treatment cycle.
Doxorubicin (Adriamycin)
Anthracycline antibiotic. Vesicant administered in free-flowing peripheral vein or central venous catheter. Several mechanisms of action: DNA intercalation, topoisomerase-mediated breaks in DNA strands, and oxidative damage due to production of free radicals.
Cyclophosphamide (Cytoxan, Neosar)
Alkylating agent; mechanism of action of active metabolites may involve cross-linking of DNA, which may interfere with growth of normal and neoplastic cells. Usually administered IV. Available PO. Use with high doses in combination with aggressive fluid hydration and monitoring of renal output. Chemically related to nitrogen mustards.
Ifosfamide (Ifex)
Alkylating agent. Inhibits DNA and protein synthesis and, thus, cell-proliferation by causing DNA cross-linking and denaturation of double helix.
Cisplatin (Platinol)
Alkylating agent. Forced diuresis with IV fluids, mannitol, and furosemide necessary to minimize renal effects.
Inhibits DNA synthesis and, thus, cell proliferation by causing DNA cross-linking and denaturation of double helix.
Etoposide (Toposar, VePesid)
VP-16 is plant alkaloid. Usually administered IV as slow or continuous infusion. Use PO in certain diagnoses. Rapid infusion causes hypotension and allergic reactions.
Inhibits topoisomerase II and causes breakage of DNA strands, arresting cellular proliferation in late S or early G2 portion of cell cycle.
Vincristine (Oncovin, Vincasar PFS)
Plant alkaloid. Inhibits cellular mitosis by inhibiting function of intracellular tubulin, binding to microtubule and spindle proteins in S phase. Administer IV only in free-flowing vein or central venous catheter. Pain due to peripheral neuropathy usually treated with acetaminophen or codeine.
Dactinomycin (Actinomycin D)
Antibiotic derived from Streptomyces bacterium. Apparently inhibits DNA synthesis.
Vesicant administered in free-flowing vein or central catheter.
Colony-stimulating factors
Class Summary
Colony-stimulating factors are used for supportive care. They act as hematopoietic growth factors that stimulate the development of granulocytes. They are used to treat or prevent neutropenia when patients are receiving myelosuppressive chemotherapy for cancer and to reduce the period of neutropenia associated with bone marrow transplantation. Colony-stimulating factors are also used to mobilize autologous progenitor cells in peripheral blood in bone marrow transplantation and in the management of chronic neutropenia.
Filgrastim (Neupogen)
G-CSF that activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils. Enhances dosage intensification with chemotherapy and speeds recovery from neutropenia.
Antiemetic agents
Class Summary
Antineoplastic-induced vomiting is stimulated through the chemoreceptor trigger zone (CTZ), which then stimulates the vomiting center (VC) in the brain. Increased activity of central neurotransmitters (dopamine in the CTZ or acetylcholine in the VC) appears to be a major mediator for inducing vomiting. After antineoplastic agents are administered, serotonin (5-HT) is released from enterochromaffin cells in the GI tract. With this release of serotonin and with its subsequent binding to 5-HT3 receptors, vagal neurons are stimulated and 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 before and after cancer treatment is often essential to ensure administration of the entire chemotherapy regimen.
Effective antiemetics include ondansetron, granisetron, metoclopramide, diphenhydramine, lorazepam, perphenazine, prochlorperazine, and trimethobenzamide.
Ondansetron (Zofran)
Selective 5-HT3 receptor antagonist that peripherally and centrally blocks 5-HT. Prevents nausea and vomiting associated with emetogenic chemotherapy for cancer. Sometimes combined with dexamethasone to potentiate antiemetic effect.
Granisetron (Kytril)
Potent serotonin 5-HT3 receptor antagonist to prevent and treat chemotherapy- and irradiation-induced nausea and vomiting.
Uroprotective antidotes
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)
Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity.
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| Primary Tumor | Regional Lymph Nodes | Distant Metastasis | Histologic Grade | |
| Stage I | Any tumor size, superficial or deep | N0 | M0 | G1 or G2 |
| Stage II | T1a (tumor < 5 cm, superficial) | N0 | M0 | G3 |
| T1b (tumor < 5 cm, deep) | N0 | M0 | G3 | |
| T2a (tumor >5 cm, superficial) | N0 | M0 | G3 | |
| Stage III | T2b (tumor >5 cm, deep) | N0 | M0 | G3 |
| Stage IV | Any tumor size, superficial or deep | N1 | M0 or M1 | G1, G2, or G3 |
| Any tumor size, superficial or deep | N0 or N1 | M1 | G1, G2, or G3 |
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