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 - 2001 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 169,500 157,400 COLO-RECTAL 135,400 50,400
9122253818924331892121833---5048503944463939554842AngiosarcomaChondrosarcoma Ewing’s Sarcoma FibrosarcomaLeiomyosarcomaLiposarcomaMesotheliomaNeurofibrosarcomaOsteogenicRhabdomyosarcoma Synovial Cell Sarcoma Undifferentiated Sarcoma # Eval % All R/Eval ADRIAMYCIN-DTIC SWOG 445 FINAL ANALYSIS BY DIAGNOSIS CR/PR 1/2---0/13/97/123/40/43/83/103/40/52/825/67 TOTAL
19172635401914200 5853504939262142.5 Head & Neck GU & Uterus Retroperitoneum Unk. Prim. & Misc. Limb Pelvis + Trunk GI Tract All # PTS. % RESPONSE LOCATION ADRIAMYCIN-DTIC IN SARCOMAS RESPONSE BY SITE OF PRIMARY
IFOSFAMIDE Response by Histology NO. EVAL PTS. % OVERALL RESPONSE 3116302229193113921 HISTOLOGY % CR 30303MFH Synovial sarcoma GI leiomyosarcoma Other leiomyosarcoma Unclassified sarcoma Benjamin et al, CCP 31:S174-179, 1993
DOSE-INTENSIVE AI IN STS Treatment Plan Adriamycin 25-30 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 1/95-12/99 122 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
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