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I Ray-Coquard, A Natukunda, JY Blay, P Casali, I Judson,

IMPACT OF CHEMOTHERAPY IN UTERINE SARCOMA (UTS): REVIEW OF 12 CLINICAL TRIALS FROM EORTC INVOLVING ADVANCED UTS COMPARED TO OTHER SOFT TISSUE SARCOMA (STS). I Ray-Coquard, A Natukunda, JY Blay, P Casali, I Judson, A Krarup Hansen, LH Lindner, AP dei Tos , H Gelderblom,

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I Ray-Coquard, A Natukunda, JY Blay, P Casali, I Judson,

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  1. IMPACT OF CHEMOTHERAPY IN UTERINE SARCOMA (UTS): REVIEW OF 12 CLINICAL TRIALS FROM EORTC INVOLVING ADVANCED UTS COMPARED TO OTHER SOFT TISSUE SARCOMA (STS) I Ray-Coquard, A Natukunda, JY Blay, P Casali, I Judson, A Krarup Hansen, LH Lindner, AP dei Tos , H Gelderblom, S Marreaud, S Litière, P Rutkowski, P Hohenberger, A Gronchi, W van der Graaf.

  2. Background *Omura 83, Sutton 88, Look 04, Sutton 05, Sutton 09, Hensley 08, Duffaud 10, Garcia del Muro 11, Pautier 13 • Uterine sarcoma : • Age 40-60 y • 5-10 % of uterine corpus malignancies • 7% of all STS , 70% LMS • Active drugs reported in litt (phase II)*: • Doxorubicin, PLD, ifosfamide, gemcitabine, trabectedin & combo Dox-Ifos, Gem-Tax, Gem-DTIC, Dox-Trabectedin • RR 11 – 54% & median PFS 3 to 6 months • No data from phase III trials in first line on RR, PFS and OS (except Muss, Cancer 1985, 100 pts)

  3. Objectives To give an overview of uterine sarcoma patient characteristics compared to other sarcoma sub-types. To evaluate the factors associated with the clinical behavior of patients with advanced or metastatic uterine sarcoma treated by first line chemotherapy Using data of 12 EORTC pooled sarcoma trials, from 1977 to 2001.

  4. Methods • Categorical variables were summarized by frequencies and percentages, continuous variables were summarized by median, range, interquartile range (IQR). • Comparisons between factors was done using chi-square or Kruskal-wallis tests. • Survival was estimated by Kaplan Meier method • Univariate and multivariate analyses were done using • Cox regression for PFS and OS • Logistic regression for RR

  5. Selection of uterine sarcoma patients 3002 patients in the EORTC sarcoma database 2827 received no prior treatment 175 received prior treatment 225 Uterine Sarcoma patients 2602 Other subtypes From 1977 to 2001

  6. Results (charact. of Ut. Sarcoma pts compared to all others)

  7. Results (charact. of UtSpatients compared to others)

  8. Overall Survival Uterine vs. other sub types

  9. Overall Survival - univariate analysis

  10. Overall Survival multivariate analysis • Better outcome for patients with WHO performance status 0 vs. 1 & 2. • Better outcome was observed for uterine patients with histopathological grade I&II compared to grade III • No significant effect of chemotherapy regimen in first line treatment observed for OS

  11. Overall Survival by prognostic factors (Grade /PS)

  12. PFS Uterine vs. other sub types

  13. PFS univariate analysis Prior RT, CT regimen, histological grade, primary site involved are not prognostic factors

  14. PFS Multivariate analysis • Better outcome for patients who had prior partial or total surgery vs. no prior surgery • Better outcome was observed for uterine patients with histopathological grade I&II compared to grade III • No significant effect of chemotherapy regimen in first line treatment observed for PFS

  15. Response to chemotherapy 27% 35% 5% 25% • 52 (23.2%) patients responded to chemotherapy • Few response among Ifosfamide alone patients • Univariate analysis identified high grade (RR 30%) vs low grade (RR 13%), non leiomyosarcoma (RR 33%) vsleio (RR 20%) and anthracyclins containing CT (RR 27%) vsifo alone (RR 5%) as predictive factors for RR

  16. Conclusions • Poor prognosis for PFS (median 4 months) & OS (10 months) • Prognostic impact of performance status and grade on OS • There was no significant effect of chemotherapy regimen observed neither for PFS nor OS. • Anthra alone remains a standard of care • Do not used Ifosfamide alone for Ut sarcoma pts • Only 25% responders to chemotherapy among the uterine sarcoma patients. • Need for new strategies !

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