Presentation on theme: "Robert S. Benjamin, M.D. Department of Sarcoma Medical Oncology The SARCOMA Center Department of Sarcoma Medical Oncology The SARCOMA Center Texas Medical."— Presentation transcript:
Robert S. Benjamin, M.D. Department of Sarcoma Medical Oncology The SARCOMA Center Department of Sarcoma Medical Oncology The SARCOMA Center Texas Medical Center Houston, Texas
Soft-Tissue Sarcomas: Should they be defined by patient age, histologic type, or neither?
ACS ESTIMATES CANCER INCIDENCE NEW CASESDEATHS NEW CASESDEATHS ALL SITES 1,268,000553,400 BONE & JOINTS 2,900 1,400 SOFT TISSUES 8,700 4,400 PROSTATE 198,100 31,500 BREAST 193,700 40,600 LUNG 169, ,400 COLO-RECTAL 135,400 50,400
Leiomyosarcoma Neurosarcoma Fibrosarcoma Synovial Sarcoma MFH Liposarcoma Rhabdomyosarcoma Angiosarcoma Unclassified Le Cesne et al, JCO 13: , NO. EVAL PTS. % OVERALL RESPONSE HISTOLOGY IFOSFAMIDE Response by Histology
DOSE-INTENSIVE AI IN STS Treatment Plan Adriamycin mg/m 2 as a 24 hr CI qd x 3, days 1-3. Ifosfamide 2.5 g /m 2 over 3 hrs qd x 4, days 1-4, with MESNA as a 24 hr CI. Prophylactic G-CSF 5 µg/Kg/d until AGC≥1500, rHTPO per phase 1 protocol. Cycles repeated every 3 weeks, Majority cycles given as an outpatient. Patel 5/00
DOSE-INTENSIVE AI IN STS Eligibility Criteria Age ≤ 65 yrs., no prior chemotherapy, prior XRT to < 20% bone marrow. Histologically confirmed sarcomas, excluding GI leios, ASPS, Clear cell sarcoma Zubrod PS 0-2. Adequate organ (especially renal) function. No other concurrent chemo/immunotherapy. Informed consent. Patel 5/00
DOSE-INTENSIVE AI IN STS Patient Characteristics 149 Patients treated on SEQUENTIAL PROTOCOLS between 1/95-12/ with measurable disease, 27 adjuvant 78 males, 71 females Median age = 46 years (range, 15-68) years Histology: 35 MFH, 25 leios, 21 Synovial, 18 Unclassified, 13 lipos, 9 angios, 28 others Patel 5/00
DOSE-INTENSIVE AI IN STS RESPONSE DATA Responses by Histology: 15/17 Synovial sarcomas (88%) 5/6 Angiosarcomas (83%) 22/32 MFH (69%) 9/15 Unclassified sarcomas (60%) 5/9 Liposarcomas (56%) 9/18 Non-GI Leiomyosarcomas (50%) 2/5 Neurofibrosarcomas (MPNST) (40%) 9/20 Other histologies (45%) Patel 5/00
Disease-Specific Therapy Future Perspectives
GI-TRACT SARCOMAS GI stromal tumor or GIST most common histology (also called leiomyosarcoma).GI stromal tumor or GIST most common histology (also called leiomyosarcoma). Present with bleeding, anemia, abdominal pain.Present with bleeding, anemia, abdominal pain. Most common in the stomach (62%), Small intestine (28%), Colon (10%).Most common in the stomach (62%), Small intestine (28%), Colon (10%). Metastasize to the peritoneum and liver; later to lung.Metastasize to the peritoneum and liver; later to lung. Refractory to standard systemic chemotherapy.Refractory to standard systemic chemotherapy. Chemoembolization of liver with cisplatin can be palliative.Chemoembolization of liver with cisplatin can be palliative.
GIST Cell of origin is the Interstitial cell of Cajal.Cell of origin is the Interstitial cell of Cajal. Constitutively expresses c-KitConstitutively expresses c-Kit c. 90% of GISTs are c-Kit positive.c. 90% of GISTs are c-Kit positive. C-Kit is one of the few tyrosine kinases specifically inhibited by Gleevec (STI-571).C-Kit is one of the few tyrosine kinases specifically inhibited by Gleevec (STI-571). Preliminary data suggest 50-90% activityPreliminary data suggest 50-90% activity An intergroup study started 12/15/00.An intergroup study started 12/15/00.
Myxoid Liposarcomas Defined by a specific translocations t (12:16) (q13;p11) (FUS-CHOP) t (12:22:20) (EWS-CHOP)Defined by a specific translocations t (12:16) (q13;p11) (FUS-CHOP) t (12:22:20) (EWS-CHOP) Metastasize to FatMetastasize to Fat –Pelvis, retroperitoneum, mediastinum Sensitive to standard chemotherapySensitive to standard chemotherapy Differentiation induced by PPAR-gamma or retinoid-X agonistsDifferentiation induced by PPAR-gamma or retinoid-X agonists Translocation a targetTranslocation a target
Angiosarcomas AngiosarcomasAngiosarcomas Standard chemotherapyStandard chemotherapy Taxol - 8/9 vs 1/27Taxol - 8/9 vs 1/27 Navelbine ?Navelbine ? InterferonInterferon Epithelioid HemangioendotheliomaEpithelioid Hemangioendothelioma EmbolizationEmbolization InterferonInterferon Newer angiogenesis inhibitorsNewer angiogenesis inhibitors