Ewing's Treatments

First Line Chemotherapy for Ewing's Sarcoma

Neoadjuvant or induction chemotherapy is chemotherapy is given prior to surgical removal of a tumor. By killing all or part of the tumor, it permits a smaller operation and makes a limb-sparing surgery safer (i.e., prevents tumor recurrence). It is common for the first 4 cycles of chemotherapy to be neoadjuvant. The term "adjuvant" refers to "an additive that enhances the effectiveness of medical treatment." The term "neoadjuvant" means "treatment given before the primary treatment."

The standard chemotherapy protocol consists of two cycles of agents: one cycle given over 1-3 days, and consists of:

• Vincristine

• Doxorubicin/Adriamycin

• Cyclophosphamide/Cytoxan given with Mesna (a side effect drug)

The second cycle is normally given over 5 days, and consists of:

• Ifosfamide/Ifex (see the related papers cited below) given with Mesna (a side effect drug)

• Etoposide/VP-16

Because this protocol frequently causes reduced production of white blood cells, most patients receive 7-10 injections of filgrastim (i.e., Neupogen) or pegfilgrastim (Neulasta).  These are given in the home or in the hospital. Anti-emetics are given to help with nausea and vomiting.

There have been and continue to be a number of clinical trials comparing different "arms" of chemotherapy for Ewing's sarcoma. One example is a multi-center Phase 3 trial comparing a 30-week treatment to a 42-week treatment.  Another example is a multi-center Phase 3 trial in Europe (click here).

Some Common and Potential Chemotherapy Agents for Ewing's Sarcoma

• Bevacizumab; Anti-VEGF

• Carboplatin; Alkylating agent; platinum compounds

• Cisplatin (a.k.a. Plantinol); Akylating agent; inhibits DNA synthesis; platinum compounds

• Cyclophosphamide/Cytoxan; Alkylating agent; replaces hydrogen atoms with an alkyl radical resulting in a defective DNA molecule; given with Mesna to protect the bladder

• Docetaxel/Taxotere; Damages microtubules, which are vital structures that are involved in cell division

• Doxorubicin/Adriamycin; "Anticancer antibiotic", anthracycline; blocks synthesis of DNA and RNA; interferes with nucleic acids

• ET-743/Ecteinascidin/Yondelis; Seems to prevent repair proteins from mending the breaks in DNA strands 

• Etoposide/VP-16; Cytostatic/antimitotic; cell poison which cells undergoing mitosis (division) are vulnerable to; block cell cycle in the phase between the last division and the start of DNA replication, and block replication of DNA

• Gemcitabine and Docetaxe

• Ifosfamide/Ifex; Alkylating agent; sticks the cancer cell's DNA together, inhibiting reproduction; replaces hydrogen atoms with an alkyl radical resulting in a defective DNA molecule; given with Mesna to protect the bladder 

• ImmTher 

• Irinotecan; a.k.a. Irinotecan hydrochloride trihydrate and CPT-11; Alkaloid; DNA topoisomerase I inhibitor, keeps the cell from making proteins

• mTOR inhibitors

• Oxaliplatin/Eloxatin; Alkylating agent; cytotoxic; platinum compounds 

• Perifisine

• TRM (TRAIL); Agonistic antibody 

• Topotecan/Hycamtin;Alkaloid; DNA topoisomerase I inhibitor, keeps the cell from making proteins 

• Vincristine; Alkaloid, mitotic inhibitor; works by inhibiting cell division

Related Websites

• Barry Sugarman's web page on the initial diagnosis of Ewing's sarcoma.

• The NCI heath professional PDQ (Physician Data Query) which lists treatment options

• The NCI patient PDQ (Physician Data Query) which lists treatment options

Related Medical Abstracts and Papers:

• 2003 abstract which states that the addition of ifosfamide and etoposide to the standard regimen significantly improves the outcome of patients with nonmetastatic Ewing's

• 1998 abstract which states that the addition of ifosfamide to vincristine, cyclophosphamide, and doxorubicin improves prognosis when compared to a previous protocol

Side Effects

Many drugs have side effects, some of which are noted above in the above links. Here are a number of drugs for dealing with the effects of chemotherapy and radiation therapy

• Anzamet

• Anti-emetic; pill/injection

• Compazine (prochlorperazine); anti-emetic; pills/injections/suppositories; frequently used for delayed nausea

• Decadron (dexamethasone): steroid; used with Kytril, Zofran, etc. to increase anti-emetic properties; used to reduce swelling and the beginning of radiation (tumors frequently swell at the beginning of radiation, causing more pain); used after a craniotomy to reduce brain swelling; used with brain mets to reduce brain swelling; see Cedars Sinai webpage and Merck's drug circular (pdf).

• Megase: prescription med to increase appetite

• Mesna: protects the bladder from possible damage to certain chemos; Given with IV (more common) or in pill form; see product label

• Zinecard (see below)

Zinecard

Basic Information

• Zinecard is also called dexrazoxane.

• Dexrazoxane is used to help prevent or lessen a toxic effect to your heart that is caused by certain medicines that are used to treat cancer; one such med is doxorubicin/Adriamycin.

• Product label

Research Information

• 2003 abstract for Japanese review article on chemotherapy-induced cardiac toxicity; the current approach to to monitor the cardiac functions.

• 2002 abstract which details results for pediatric acute lymphoblastic leukemia (ALL) patients, half of them received Zinecard with their doxorubicin and the other half didn't.  The two groups were assessed for myocardiocyte injury by measuring a particular protein which is not normally present in serum except after cardiac injury.  Patients treated with doxorubicin alone had a higher rate of the protein (45% verses 23%)

Current Clinical Trials

• Dexrazoxane (zinecard) is being used in a Phase 2 trial including ImmTher: Vincristine, Doxorubicin, Cyclophosphamide and Dexrazoxane (VACdxr) With or Without ImmTher for Newly Diagnosed High Risk Ewing's Sarcoma