1 / 81

Current Opinion in the Colorectal Cancer Treatment

Dott. Carlo Garufi Oncologia Medica C Istituto Regina Elena – Roma garufi@ifo.it. Current Opinion in the Colorectal Cancer Treatment. Treatment Strategies in ACC in2007. III. II. I. Adjuvant CHT. IFL+BEVA. CETU +IRI. FOLFOX. FOLFIRI+BEVA. CETU +IRI. FOLFOX. FU/FA+ BEVA. FOLFOX.

eshana
Download Presentation

Current Opinion in the Colorectal Cancer Treatment

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. Dott. Carlo Garufi Oncologia Medica C Istituto Regina Elena – Roma garufi@ifo.it Current Opinion in the Colorectal Cancer Treatment

  2. Treatment Strategies in ACC in2007 III II I Adjuvant CHT IFL+BEVA CETU+IRI FOLFOX FOLFIRI+BEVA CETU+IRI FOLFOX FU/FA+BEVA FOLFOX FOLFIRI CETU+IRI 5FU/FA Capecitabine or FOLFOX CAPE+BEVA FOLFOX CETU+IRI FOLFIRI FU/FA CAPE CETU+IRI FOLFOX IRI O FOLFIRI FOLFOX CETU + IRI FOLFOX+BEVA FOLFOX CETU+IRI FOLFIRI CETU + IRI FOLFOX

  3. Cancro colon-retto avanzato:tutti i trattamenti sono uguali? FOLFOX = FOLFIRI CAPOX = CAPIRI Tournigand 2004, Colucci 2005, Grothey 2004 FOLFOX > IFL Goldberg 2004 The use of all available drugs is strongly suggested Grothey 2004

  4. Statistical Considerations

  5. Cancro colon-retto avanzato: ruolo del bevacizumab BEVA+ IFL >IFL in Prima Linea Hurwitz H 2004 BEVA + FOLFOX4 >FOLFOX4 in II linea Giantonio BJ 2005 ma ……

  6. The addition of Bevacizumab to IFL increases PFS and OS

  7. Saltz L ASCO 2007

  8. Saltz L ASCO 2007

  9. Aggiunta di BEVA alle doppiettein prima linea • Bevacizumab aumenta OS se usato con IFL • Non aumenta OS se usato con XELOX o FOLFOX4

  10. Canro colorettale e Cetuximab Cetuximab is the most active drug in pretreated patients Lentz 2005 Cetuximab + FOLFOX4 is a very active regimen (Resp Rate >60%) Colucci 2006, Tabernero 2004

  11. CRYSTAL Trial: Study Design Cetuximab + FOLFIRI Cetuximab IV 400 mg/m2 on day 1, then 250 mg/m2 weekly+ irinotecan (180 mg/m2) + 5-FU (400 mg/m2 bolus + 2400 mg/m2 as 46-hr continuous infusion) + FA every 2 weeks EGFR-expressing metastatic CRC R FOLFIRI irinotecan (180 mg/m2) + 5-FU 400 mg/m2 bolus + 2400 mg/m2 as 46-hr continuous infusion) + FA every 2 weeks Stratification factors: • Regions • ECOG PS Populations • Randomized patients n=1217 • Safety population n=1202 • ITT population: n=1198 Van Custen et al, ASCO 2007

  12. CRYSTAL Trial: Study Endpoint • Primary endpoint: • Progression-free survival time (as assessed by blinded independent review) • Secondary endpoints: • Overall response rate (independently reviewed) • Disease control rate (CR+PR+SD) • Overall survival time • Quality of life (EORTC QLQ C30) • Safety

  13. CRYSTAL Trial: Primary End-Point PFS

  14. CRYSTAL trial:Independent Assessment of Response p-value* = 0.0038 *Cochran-Mantel-Haenszel (CMH) test ** DCR: disease control rate

  15. CRYSTAL Trial: Conclusions • The CRYSTAL trial met its primary objective of demonstrating that the addition of cetuximab to FOLFIRI in the first-line treatment of EGFR-detectable mCRC significantly increased PFS • There was a 15% risk reduction for progression in patients treated with cetuximab plus FOLFIRI compared to FOLFIRI • The addition of cetuximab to FOLFIRI was associated with: • Higher response rates (p=0.0038) • Threefold higher R0 resection rates for initially unresectable disease (p=0.0034) • Skin reactions showed a strong correlation with efficacy

  16. Differences in Treatment Strategies Between US and Europe A. Grothey WCGC 2007

  17. Unsolved Questions • Is there a clear advantage in survival with the use of polichemotherapy rather then monochemotherapy as first line treatment? (Seymour 2007, Punt 2007) • What is the role of the stop and go strategy? (GISCAD 2006, ) • What is the role of triplet in patients with liver metastases? (Falcone A. 2006, Garufi C 2007) • Is colorectal cancer a unique clinical disease?

  18. Lancet 2007

  19. FOCUS TRIAL

  20. CAIRO TRIAL

  21. CAIRO TRIAL

  22. Which strategy as first line treatment? • Perhaps the answer is to define a “Minimal Therapy” or an “Intense Therapy” • Introduction of the concept of “Continuum Treatment” (Hoff ASCO 2007)

  23. (Hoff ASCO 2007)

  24. (Hoff ASCO 2007)

  25. (Hoff ASCO 2007)

  26. Unsolved Questions • Is there a clear advantage in survival with the use of polichemotherapy rather then monochemotherapy as first line treatment? (Maughan T. 2003) • What is the role of the stop and go strategy? (GISCAD ASCO2006, OPTIMOX2 ASCO 2007) • What is the role of triplet in patients with liver metastases? (Falcone A. 2006, Garufi C) • Is colorectal cancer a unique clinical disease?

  27. Rationale • Chemotherapy-free intervals have been previously • studied in patients receiving 5-FU based therapy • Hejna et al. (Br J Cancer 1998) • Maughan et al. (Lancet 2003) • New combination therapies have improved survival • but there is still the risk of cumulative toxicities like • Oxaliplatin sensory neuropathy • Clinical rationale: quality of life preservation, • costs reduction and social impact improvement

  28. Continuos vs Intermittent Therapy ? MRC Trial “Our findings provided no clear evidence of benefit in continuing therapy indefinitly until disease progression” Maugan et al., Lancet 2003

  29. GISCAD Trial: Design (ASCO 2006) FOLFIRI N=336 R Evaluation 4 mos Primary end point: OS Non inferiority : 15< Median OS (months)< 11

  30. Greem ASCO 2007 Discussant

  31. STOP and GO STRATEGY • At this time there are no clear advantage from a stop and go strategy. It seems that continuing treatment until progression, if not hampered by severe toxicity, is still a valid option

  32. We should consider Stage IV different groups of colorectal cancer patients • Clinical History (PS, comorbidity, age) • Interdisciplinary Teams (surgery and/or RT) • Different median survival (<12 e >24 mesi) • Necessity to identify new prognostic factors

  33. We need new trials for old and new Prognostic Factors • Gender(Giacchetti S. et al JCO 2006) • Hb(Tampellini M. et al Br J Cancer 2006) • LDH (Koehne et al ASCO 2006) • Resectability(Poston G et al JCO 2006) • GenicPolimorphysm (Toffoli G et al JCO 2006)

  34. Clinical determinants of survival in patients with 5-fluorouracil- based treatment for metastatic colorectal cancer: results of a multivariate analysis of 3825 patients C.-H. Kohne, D. Cunningham, F. Di Costanzo, B. Glimelius, et al Ann. Onc.,  2002; 13(2): 308 - 317.

  35. Diferent Stage IV Disease in Different Patients • Disseminated Disease • Local Recurrences • Peritoneal Carcinosis • Non-measurable Disease • Lung Metastases • Liver Metastases • Resected • Resectable • Non-resectable

  36. Diferent Stage IV Disease in Different Patients • Disseminated Disease • Local Recurrences • Peritoneal Carcinosis • Non-measurable Disease • Lung Metastases • Liver Metastases • Resected • Resectable • Non-resectable

More Related