Ewing's Sarcoma: Treatment


  • Overview
  • Chemotherapy
  • Surgery
  • Radiation

First Line Treatments

The treatment for Ewing's sarcoma, like the disease itself, is aggressive. It is normally 9-12 months long and can consist of 10-14 cycles of chemotherapy, resection surgery to remove the primary tumor, and radiation to the local site. The chemotherapeutic agents used differ a bit depending on the specific protocol the doctor is following. Each of these approaches is discussed separately on this page.

Dr. Randall, in his article, "Ewing’s Sarcoma Family of Tumors (ESFT)," states that, "It is critical that a patient diagnosed with ESFT is treated at a center very familiar with this disease." He goes on to state, "Advances in chemotherapy (CTx) have significantly improved survival. Surgical removal of the primary tumor generally occurs after a course of initial chemotherapy. Chemotherapy is started first to attack any potential tumor cells that have broken off from the main tumor (metastasized) but have not yet been detected by the staging studies."

Second Line Treatments

If the first line treatment isn't successful, which can be seen after 2-4 cycles of chemotherapy by scanning the primary tumor for growth or development or growth of metastases, then the chemotherapy regimen is frequently changed to another regimen. There is not one particular regimen that all or most oncologists use; a number of them have similar clinic trial results, i.e., have been shown to be equally as good. Once a chemotherapy is found which the tumors respond to, the surgery and radiation components are continued.

Clinical Trials

When tumors fail to respond to the first and second line treatments, patients may turn to clinical trials.

First Line Chemotherapy for Ewing's Sarcoma

"Neoadjuvant" or "induction chemotherapy" is chemotherapy that 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:

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

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). Recently, one study indicated that receiving treatment every two weeks could improve overall survival for Ewing's sarcoma patients.

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 Docetaxel
  • 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
  • Perifosine
  • 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

Surgery

If possible, surgery is used to remove the primary tumor, and the surgery is called a tumor resection.  If the tumor is in a bone, the surgery frequently involves limb-sparing surgery and, potentially, donor bones.

Radiation Treatment for Ewing's Sarcoma

Radiation, is given as frequently as once a day for 5 minutes, every day for some number of days. For Ewing's sarcoma where the primary tumor is an external limb, radiotherapy is frequency done to the site of the primary tumor for 31 treatments.

Related Material

  • 2003 abstract stating that radiation to the local site for Ewing's may improve local control; based on large European trials