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Sarcoma Studies

Program Director:
Eilber, Frederick M.D.
Eckardt, Jeff M.D.
Selch, Michael M.D.
Forsher, Charles M.D.
Nelson, Scott M.D.

Contact Phone Number
(310) 825-7086

Description of Clinical Program
Clinical studies with skeletal and soft tissue sarcoma continue to expand on the theme of preoperative therapy. For malignant bone tumors, significant progress has been realized by the integration of the drug ifosfamide into existing chemotherapy protocols. Prior studies had established the efficacy of adriamycin, high dose methotrexate, and cis-platinum preoperatively in a systemic fashion. The addition of newer agents to existing chemotherapy regimens has achieved an even higher degree of preoperative tumor kill. With prior chemotherapeutic regimens, approximately 65% of the patients achieved a complete pathologic response. With the addition of ifosfamide, this number has risen to approximately 80%. An additional area of interest in clinical research has been the use of expandable endoprosthesis in children (who are not skeletally mature) with bone tumors. Implantation of these devices, which can be lengthened as the child grows, has permitted limb salvage procedures on patients who otherwise would have had amputations.
For soft tissue sarcoma, the major progress has also been the integration of the drug ifosfamide into preoperative protocols. The use of adriamycin, cis-platinum, and radiation therapy achieved a complete response histologically in approximately 15% of patients. The addition of ifosfamide has improved this dramatically to approximately 50%. This, integrated with more standard doses of radiation therapy, has allowed the previous limb salvage protocols, which were exclusively for extremity lesions, to now be applied to more general and more difficult areas such as the head and neck and retroperitoneum. Continued studies are underway with the use of radioactive isotopes to try to image these tumors preoperatively. The use of thallium scans in a sequential and prospective fashion have correlated extremely well with the eventual pathologic evaluation of tumor necrosis.
A recent advance is the use of STI-571 in the treatment of Gastrointestinal Stromal Tumors (GIST). STI-571 is a small molecule that has been demonstrated to be a highly selective inhibitor of certain protein tyrosine kinases. STI-571 has been found to inhibit kinase action of the bcr-abl protein found in CML, the platelet-derived growth factor (PDGF) receptor and KIT, the product of the c-kit proto-oncogene. GIST tumors have a mutation in the c-kit proto-oncogene in the vast majority of cases. Patients with malignant GISTs have a poor outcome and there has been no effective treatment for patients with unresectable or metastatic disease. A recent Phase II trial has documented significant activity of STI-571 in GIST. A Phase III trial is currently being performed to compare different doses of STI-571.

Research Programs

Evaluation of a translocation abnormality in synovial cell sarcomas to correlate with patient outcome and drug resistance.

Clinical Trials

Phase III Randomized, Intergroup Trial Assessing the Clinical Activity of STI-571 at two dose levels in patients with unresectable or metastatic GIST expressing the KIT receptor tyrosine kinase (CD117).

Phase II Study of Adjuvant STI-571 in Patients Following Completely Resected High-Risk Primary Gastrointestinal Stromal Tumor (GIST).

Publications

Eilber FC, Rosen G, Forscher C, Nelson S, Dorey F, Eilber FR. Surgical resection and intraperitoneal dissection for recurrent abdominal sarcoma. Surgical Oncology, 26:645-650, 1999.

Eilber FC, Eckardt J, Rosen G, Nelson S, Selch M, Eilber FR. High grade extremity sarcoma: Treating tumors of the flexor fossa. J Surg Oncol, 8:211-214, 2000.

Eilber FC, Rosen G, Forscher C, Nelson S, Dorey F, Eilber FR. Recurrent gastrointestinal sarcomas. Surgical Oncology, 7(2):73-75, 2000.

Eilber FC, Eilber KS, Eilber FR. Retroperitoneal sarcomas: Current treatment options in oncology. Surgical Oncology, 1(3):274-278, 2000.

Eilber FC, Rosen G, Eckardt J, Forscher C, Nelson S, Selch M, Dorey F, Eilber FR. Treatment induced pathologic necrosis: A predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high grade extremity soft tissue sarcomas. Journal of Clinical Oncology, in press, 2001.

Education

The Musculoskeletal Research Meeting is held Thursdays at 430pm in the conference room of Radiation Oncology, Level B2, 200 Med Plaza. Surgeons, medical oncologists, radiation oncologists, radiologists and pathologists discuss cases and determine treatment plans for each patient.

Surgical Oncology


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