1 / 85

La chemioterapia neoadiuvante e adiuvante nei sarcomi delle parti molli Padova, 30 Maggio, 2008 A.Buonadonna, CRO

La chemioterapia neoadiuvante e adiuvante nei sarcomi delle parti molli Padova, 30 Maggio, 2008 A.Buonadonna, CRO-Aviano. Adjuvant chemotherapy in STS. Topics Review 1 st Italian randomized study National Survey 2 nd Italian, neo-adjuvant, randomized trial EORTC Trial

hollie
Download Presentation

La chemioterapia neoadiuvante e adiuvante nei sarcomi delle parti molli Padova, 30 Maggio, 2008 A.Buonadonna, CRO

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. La chemioterapia neoadiuvante e adiuvante nei sarcomi delle parti molli Padova, 30 Maggio, 2008 A.Buonadonna, CRO-Aviano

  2. Adjuvant chemotherapy in STS • Topics • Review • 1st Italian randomized study • National Survey • 2nd Italian, neo-adjuvant, randomized trial • EORTC Trial • Conclusions

  3. Adjuvant chemotherapy in STS For adult soft tissue sarcomas , stage III encompasses tumors larger than 5 cm, high grade (3-4), located deep to the superficial fascia, that have no evidence of distant metastasis. After definitive loco-regional treatment only, approximately 50% of these patients will develop a recurrence, and 45% will die of sarcoma within 5 years. Greene FL, Page DL, Fleming ID, et al. (2002) AJCC cancer staging handbook, 6th edn. Berlin, Heidelberg, New York: Springer.

  4. Chemioterapia adiuvante: Studi di Ia generazione(1)

  5. Chemioterapia adiuvante: Studi di Ia generazione(2)

  6. Trials included in the meta-analysis: 14 • Single patient data records analyzed: 1568 • Reliability: evaluated 98% of included patients • ADM total dose: 200-500 mg/m2 • ADM per cycle: 50-90 mg/m2 either as single agent or in combination

  7. Sarcoma Meta-analysis Collaboration (Lancet, 350:1647-54, 1997)

  8. Sarcoma Meta-analysis Collaboration (Lancet, 350:1647-54, 1997)

  9. Sarcoma Meta-analysis Collaboration (Lancet, 350:1647-54, 1997)

  10. Sarcoma Meta-analysis Collaboration (Lancet, 350:1647-54, 1997)

  11. Chemioterapia adiuvante: Meta-analisi Sarcoma Metanalysis Collaboration III (Lancet, 350:1647-54, 1997)

  12. SECOND GENERATION TRIALS II

  13. SECOND GENERATION TRIALS IV

  14. SECOND GENERATION TRIALS • Similarities • More homogeneous selection criteria • Use of Ifosphamide • 2 drugs combinations • Use of Growth factors • Differences • Dose intensity • Sequence of approaches( S/RT/CT)

  15. Controversy: Adjuvant chemotherapy in STS • Topics • Review • 1st Italian randomized study • National Survey • 2nd Italian, neo-adjuvant, randomized trial • EORTC Trial • Conclusions

  16. S. Frustaci et al. JCO; 19: 1238-1247, 2001

  17. ADJUVANT CHEMOTHERAPY IN STS INCLUSION CRITERIA • Age >16 <65 years • PS <2 ECOG • High grade (G3-G4 Broder), subfascial spindle cell and polymorphous locally controlled sarcomas • Extremities and/or girdles • No previous radio/chemotherapeutic treatment • Primary >5 cm; relapse of any dimension • Written informed consent 4/97

  18. 1ST ITALIAN ADJUVANT STUDY • Chemotherapy • (one cycle every 21 days) • Epirubicine 60mg/m2/die, days 1 and 2 • Ifosfamide 3g/m2/die, days 1, 2, 3 • Mesna 1000mg/m2 x 3/die, days 1, 2, 3 • Hydration with  2000 cc/die during days 1, 2, 3 • Anti-HT3 and corticosteroids • G-CSF from day +7 to complete haematological recovery • Adequate dose modifications according to the nadirs

  19. ADJUVANT CHEMOTHERAPY IN STS 1st Italian Sarcoma Group Trial: Dose intensity MEDIAN RELATIVE DOSE-INTENSITY (%) I Cycle II Cycle III Cycle IV Cycle Average EPI 88 83.1 75.7 73.2 80.0 120/m2 (47.2-106) (37.5-107.0) (36.6-103.4) (25-104.3) IFO 89.1 89.5 86.2 82.1 86.7 9g/m2 (49.8-101.6) (55.5-107.0) (60-104.5) (30.6-103.4) Average 90.9 85.2 80.9 77.7 83.7 R.D.I. Range (49.9-104.6) (55.5-107.1) (52.2-103.4) (37.4-103.8)

  20. ADJUVANT CHEMOTHERAPY IN STS 1st Italian Trial: Disease free survival JCO, 2001, Vol. 19, N° 5, Median F.U.=59 m Minimum F.U.=36 m P=0.04

  21. ADJUVANT CHEMOTHERAPY IN STS 1st Italian Trial: Overall survival JCO, 2001, Vol. 19, N° 5, Median F.U.=59 m Minimum F.U.=36 m P = 0.03

  22. The First Adjuvant I.S.G. Trial; 06/92- 11/96 Summary of performed analyses

  23. Adjuvant therapy in soft tissue sarcomas ISG Study:06/’92-11/’96 Analysis of 09/02 Disease free survival Median follow-up: 89.4m Treat F.U. N°pts 53 51 Cens 24 19 Events 29 32 m.DFS 48.8 16.2 p=0.08

  24. Adjuvant therapy in soft tissue sarcomas ISG Study:06/’92-11/’96 Analysis of 09/02 Overall survival Median follow-up: 89.4m Treat F.U. N°pts 53 51 Cens 31 23 Events 22 28 m. OS n.r. 50.4 p=0.07 5 years OS: 66 vs 46% (p=0.04)

  25. 1st ISG Study: 06/’92-11/’96; Analysis of 09/02 Subgroup analysis: Efficacy of chemotherapy 7 pts never started CT because of early relapse or refusal Median follow-up: 89.4m Treat F.U. N°pts 46 51 Cens 28 23 Events 18 28 m.Surv n.r. 54.3 p=0.038 Overall Survival

  26. 1st ISG Study: 06/’92-11/’96 Analysis of 09/02 Subgroup analysis: Dose intensity of chemotherapy Median follow-up: 89.4m Overall Survival

  27. 1st ISG Study: 06/’92-11/’96 Analysis of 09/02 Subgroup analysis: Dose intensity of chemotherapy Median follow-up: 89.4m MEDIAN RELATIVE D.I. % Cycle 1st 2nd 3rd 4th Average EPI 88 83.1 75.7 73.2 80.0 IFO 89.1 89.5 86.2 82.1 86.7 % 90.9 85.2 80.9 77.7 83.7 Overall Survival

  28. Adjuvant therapy in soft tissue sarcomas 1st ISG Study: 06/’92-11/’96 Analysis of 09/02 Post relapse survival Treat F.U. N°pts 29 32 Cens 7 4 Events 29 32 m.Surv 21.8 17.8 p=0.37

  29. Controversy: Adjuvant chemotherapy in STS • Topics • Review • 1st Italian randomized study • National Survey • 2nd Italian, neo-adjuvant, randomized trial • EORTC Trial • Conclusions

  30. Survey dell’Italian Sarcoma Group. • - Aims: to verify the reproducibility, efficacy, reliability of the prospective trial when applied spontaneously outside the protocol. • Period: 11/’96 to 06/’99 • - Methods: • 1)Call for data launched in June ‘99 • 2) Prospective data collection, spontaneous referral of unregistered patients, homogeneous selection criteria and treatment modality.

  31. UPDATED RESULTS OF THE ITALIAN SURVEY • Chemotherapy • (one cycle every 21 days) • Epirubicine 60mg/m2/die, days 1 and 2 • Ifosfamide 3g/m2/die, days 1, 2, 3 • Mesna 1000mg/m2 x 3/die, days 1, 2, 3 • Hydration with  2000 cc/die during days 1, 2, 3 • Anti-HT3 and corticosteroids • G-CSF from day +7 to complete hematologic recovery • Adequate dose modifications according to the nadirs

  32. UPDATED RESULTS OF THE ITALIAN SURVEY • Evaluation of the “post-trial” treatment • TREATMENT • - Completed CT (5 cycles) 43/55 (78.2%) • - Interrupted • - for toxicity G3 - G4 8/55 • - for other reasons 4/55

  33. UPDATED RESULTS OF THE ITALIAN SURVEY Dose Intensity Cycles I II III IV Average EPI 96.4 94.2 86.6 77.7 88.7 Range (38.1-116) (48.3-111) (43.5-106) (24-109) IFO 99.3 95.8 91.1 74.4 90.1 Range (38.1-117) (41.6-111) (26.6-105) (23-105) Median 97.9 94.8 88.2 75.0 89.4 Range (38.1-116.5) (52-111) (35.5-105.5) (23.5-105) (52 - 116)

  34. UPDATED RESULTS OF THE ITALIAN SURVEY Survival: comparison with CNR study(11/98) 100 TREATMENT 90 CONTROL 80 SURVEY 70 60 % OS 50 40 30 20 10 0 0 12 24 36 48 60 72 84 96 MONTHS

  35. Controversy: Adjuvant chemotherapy in STS • Topics • Review • 1st Italian randomized study • National Survey • 2nd Italian, neo-adjuvant, randomized trial • EORTC Trial • Conclusions

  36. Controversy: Adjuvant chemotherapy in STS Italian Sarcoma Group Localized adult soft tissue sarcoma of the extremities and trunk: Integrated approach of 3 neodjuvant cycles or 3 neoadjuvant and 2 adjuvant cycles. Controlled prospective randomized study Clinical coordinatorsCoordinating and Data Center S.Frustaci, Aviano P.Valagussa, Milano A.Gronchi, Milano M.Mercuri, Bologna Statistical analysis P.Verderio, Milano Activation September 2001

  37. Controversy: Adjuvant chemotherapy in STS • Italian Sarcoma Group • Localized adult soft tissue sarcoma of the extremities and trunk: • Local Treatments (multiple options) • RADICAL SURGERY • SEQUENTIAL APPROACH Surgery and Radiation therapy: • - Post-op radiation therapy • - Peri-op brachyther.& post-op RT • - Pre-op radiation therapy • Chemo-ipertermic perfusion and Surgery • INTEGRATED APPROACH Synchronous chemo & pre-op RT

  38. Controversy: Adjuvant chemotherapy in STS • Localized adult soft tissue sarcoma of the extremities and trunk: • Inclusion Criteria • Adult STS, primary or relapsed or considered inadequately locally treated. • Spindle or polimorphous (Fibrosarcoma, MFH, Lipos., Leiomios., Synovial s., m. Schwannoma, A ngiosarcoma, Rabdomios.) • Diagnosys in accordance with Enzinger e Weiss criteria(10). • High grade (2-3/3, according to Coindre et al.) (11). • Deep seated • SITE: limbs, girdles, sup. Trunk. • SIZE: primary >5 cm (Clinical evalutaion:CT, RM) • relapse of any size. • Age: > 18, < 65 years. • Performance status <1 secondo ECOG (12). STAGE III only

  39. Controversy: Adjuvant chemotherapy in STS Italian Trials

  40. Controversy: Adjuvant chemotherapy in STS

  41. Controversy: Adjuvant chemotherapy in STS Italian Sarcoma Group Localized adult soft tissue sarcoma of the extremities and trunk: Integrated approach of 3 neodjuvant cycles or 3 neoadjuvant and 2 adjuvant cycles. Controlled prospective randomized study Clinical coordinatorsCoordinating and Data Center S.Frustaci, Aviano P.Valagussa, Milano A.Gronchi, Milano M.Mercuri, Bologna Statistical analysis P.Verderio, Milano Activation September 2001

  42. Controversy: Adjuvant chemotherapy in STS Italian Sarcoma Group Localized adult soft tissue sarcoma of the extremities and trunk: Integrated approach of 3 neodjuvant cycles or 3 neoadjuvant and 2 adjuvant cycles. Controlled prospective randomized study Clinical coordinatorsCoordinating and Data Center S.Frustaci, Aviano P.Valagussa, Milano A.Gronchi, Milano M.Mercuri, Bologna Statistical analysis P.Verderio, Milano Activation September 2001 Local Treatments (multiple options) RADICAL SURGERY SEQUENTIAL APPROACH Surgery and Radiation therapy: - Post-op radiation therapy - Peri-op brachyther.& post-op RT - Pre-op radiation therapy Chemo-ipertermic perfusion and Surgery INTEGRATED APPROACH Synchronous chemo & pre-op RT

  43. Controversy: Adjuvant chemotherapy in STS

  44. Controversy: Adjuvant chemotherapy in STS

  45. Controversy: Adjuvant chemotherapy in STS

  46. Controversy: Adjuvant chemotherapy in STS

  47. Controversy: Adjuvant chemotherapy in STS

  48. Controversy: Adjuvant chemotherapy in STS • Topics • Review • 1st Italian randomized study • National Survey • 2nd Italian, neo-adjuvant, randomized trial • - EORTC Trial • Conclusions

More Related