Pediatric Rhabdomyosarcoma Medication

Updated: Dec 08, 2022
  • Author: Timothy P Cripe, MD, PhD, FAAP; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Medication Summary

Standard therapy for rhabdomyosarcoma (RMS) includes chemotherapy combined with surgical resection, radiotherapy, or both for local control, if necessary. These modalities have not improved survival rates in patients with metastatic disease; however, new agents active against rhabdomyosarcoma are being sought, and agents are being tested in phase I and II clinical trials. Novel therapies in development include oncolytic viruses [35] and immunotherapies, such as monoclonal antibodies [36] and dendritic-cell vaccines. In addition, evidence suggests that some targeted agents may be active in rhabdomyosarcoma, including proteosome inhibitors, [37] and anti-insulinlike growth factor receptor (IGFR) antibodies. [38] The role of oral maintenance therapy may be useful in controlling metastatic disease but has not been confirmed. [39]


Antineoplastics agents

Class Summary

This therapy is aimed at killing tumor cells. Cancer chemotherapy is based on an understanding of how tumor cell grow and of 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) and, finally, mitotic cell division (phase M) occurs.

The cell-division rate varies for different tumors. Tumors of most common cancers grow slowly compared with normal tissues, and the rate of growth may decrease further in large tumors. This difference allows normal cells to recover from chemotherapy more quickly than malignant cells can and is the rationale behind current cyclic dosing schedules.

Antineoplastic agents interfere with cell reproduction. Some agents are phase specific, whereas others (eg, alkylating agents, anthracyclines, cisplatin) are not. Cellular apoptosis (ie, programmed cell death) is a potential mechanism of many antineoplastic agents. [40] Those listed here are the standard active agents, although others, such as irinotecan, appear useful, are under investigation, and are now being included in all high-risk clinical trials. [41] The addition of agents known to be active in rhabdomyosarcoma, such as ifosfamide and topotecan, do not appear to provide additional benefit to intermediate-risk patients when added to the standard regimen of vincristine, actinomyocin, and cyclophosphamide. [5]

Vincristine (Oncovin)

Inhibits tubulin polymerization, targeting dividing cells. Acts as vesicant.

Dactinomycin (Cosmegen, actinomycin D)

Antibiotic derived from Streptomyces bacteria.

Cyclophosphamide (Cytoxan)

Alkylating agent believed to be cytotoxic to dividing cells by cross-linking cellular DNA. Processed in liver to active metabolites. Byproducts (eg, acrolein) accumulate in bladder and cause cystitis.

Etoposide (Toposar, VP16)

Inhibits topoisomerase II and therefore toxic to cells undergoing DNA replication.

Ifosfamide (Ifex)

Alkylating agent. Inhibits DNA and protein synthesis and therefore cell proliferation by causing DNA cross-linking and denaturation of double helix.

Irinotecan (Camptosar, CPT-11)

Topoisomerase I inhibitor. Use in RMS currently investigational.


Uroprotective antidote

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 to be responsible for urotoxicity.

Mesna (Mesnex)

Inactivates acrolein and prevents urothelial toxicity without affecting cytostatic activity. Sulfhydryl compound that accumulates in urine and inactivates toxic byproducts of cyclophosphamide and ifosfamide.


Colony-stimulating factors

Class Summary

These agents act as hematopoietic growth factors that stimulate the development of granulocytes. They are used to treat or prevent neutropenia when patients are receiving myelosuppressive cancer chemotherapy and to reduce the period of neutropenia associated with bone marrow transplantation. They are also used to mobilize autologous peripheral blood progenitor cells for bone marrow transplantation and in the management of chronic neutropenia. They shorten the time to neutrophilic recovery after chemotherapy.

Filgrastim (Neupogen)

Granulocyte colony-stimulating factor (G-CSF) that activates and stimulates production, maturation, migration, and cytotoxicity of neutrophils. Better tolerated than alternative GM-CSF.