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Squamous Cell H&N Cancer Hypopharynx Therapeutic Approach

Squamous Cell H&N Cancer Hypopharynx Therapeutic Approach. Ricardo Hitt MD, PhD Hospital Universitario 12 Octubre MADRID. STATEMENTS 2008. Squamous Cell H&N Cancer Hypopharynx. The majority of hypopharyngeal lesions originate in the pyriform sinus. On admission, 75% of the patients have

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Squamous Cell H&N Cancer Hypopharynx Therapeutic Approach

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  1. Squamous Cell H&N CancerHypopharynxTherapeutic Approach Ricardo Hitt MD, PhD Hospital Universitario 12 Octubre MADRID STATEMENTS 2008

  2. Squamous Cell H&N CancerHypopharynx • The majority of hypopharyngeal lesions originate in the pyriform sinus. • On admission, 75% of the patients have clinically positive nodes. • There is no difference in the risk of neck metastases by T stage.

  3. Treatment of Head and Neck CancerMultidisciplinary Radiation oncologist Medical oncologist Decision making HN surgeon

  4. Treatment of Head and Neck CancerMultidisciplinary CLINICAL TRIAL STANDARD TREATMENT Decision making

  5. HYPOPHARYNGEAL CANCER HEAD AND NECK CANCER OROPHARYNX ORAL CAVITY LARYNX HIPOPHARYNX

  6. HYPOPHARYNGEALCANCER OBJECTIVES CURE ORGAN PRESERVATION QUALITY OF LIFE

  7. HYPOPHARYNGEALCANCER TODAY ,WITH MEDICAL TREATMENT OVERALL SURVIVAL ORGAN PRESERVATION NEW OBJECTIVE:Increase Overall Survival and Organ Preservation HOW???

  8. J. L. Lefebvre, D. Chevalier, B. Luboinski, L. Traissac, G. Andry, D. De Raucourt, L. Collette, J. Bernier, EORTC Head and Neck Cancer Cooperative Group. F R A N C E Is Laryngeal Preservation (LP) With Induction Chemotherapy (ICT) Safe in the Treatment of Hypopharyngeal SCC? Final Results of the Phase III EORTC 24891 Trial. Last Update: ASCO 2004

  9. STUDY DESIGN Surgery + RT N = 94 R LP: PF + RT RXT 70 Gy ± salvage surgery N = 100 CR* PR* NC* CR* Cycle 1 Cycle 2 PR* Cycle 3 CR* PD* NC/PD* PR/NC/PD* • Primary endpoint: OS (non-inferiority of LP) • Secondary endpoints: PFS, larynx preservation Surgery + Postoperative RXT Lefebvre JL, et al. JNCI 1996; 88:890-8; Lefebvre JL, et al. ASCO 2004: Abstract 5531.

  10. PATIENT CHARACTERISTICS Lefebvre JL, et al. ASCO 2004: Abstract 5531.

  11. Overall survival Disease-free survival 100 90 100 90 80 80 70 70 60 60 50 50 40 40 30 30 20 20 10 10 0 (years) 0 (years) 0 2 4 6 8 10 12 14 16 0 2 4 6 8 10 12 14 16 O N Number of patients at risk : O N Number of patients at risk : 88 94 37 25 16 6 5 1 0 Surgery 81 94 49 36 26 14 9 5 3 Surgery 88 100 47 32 19 10 5 2 1 Preservation 83 100 62 47 27 17 8 4 1 LP OVERALL SURVIVAL AND DFS Hazard Ratio: 0.83 (95% CI: 0.62-1.12) HR: 0.88 (95% CI: 0.65 - 1.19) P=0.0015 for non-inferiority of LP Larynx preservation Larynx preservation Median, 44 mo Surgery Surgery Median, 25 mo Lefebvre JL, et al. ASCO 2004: Abstract 5531. Lefebvre JL, et al. ASCO 2004: Abstract 5531.

  12. SURVIVALPHARYNGEAL SCC Devita. 7th Edition

  13. SURVIVAL PHARYNGEAL SCC Devita. 7th Edition

  14. Background Historical standard treatment (80') for locallyadvanced squamous cell carcinoma of the headand neck (SCCHN) Operable disease Surgery radiation (RT) Inoperable disease RT (5 yr surv. 10%-20%) Concomitant CT/RT standard for inop. Pts (90’)(5yr surv. 20%- 30% )

  15. ASCO 1982: The Platinum Revolution 35 previously untreated pts: 3 cycles cisplatin-5FU (CF) Response > 50% Complete response 94% 63% Decker D et al. ASCO Annual Meeting.Saint Louis 1982, Abstract C-757 Decker DA et al. Cancer 1983;51:1353-5 60 tumors treated with platinum-based chemotherapy 42 responses > 50% 18 responses < 50% after RT after RT Ensley J et al. ASCO Annual Meeting.Saint Louis 1982, Abstract C-767 Ensley JF et al. Cancer 1984;54:811-4 97% 6%

  16. Rationale for induction CT -1- Induction CT: high RR ( 70%-80%); RC (5% - 30%) 1- 4 cycles prior to RT Subsequent RT or surgery not compromised Not clear if local control increased Response to induction CT predicts response to RT Part of a larynx preservation strategy

  17. Rationale for induction CT -2- Induction CT reduces incidence of distant metastases Patient selection crucial (dist .met. 30%-40%) T bulky ; N (bilateral, high number, capsula rupture),Site (hypopharynx), other markers From meta-analysis: induction with PF 5% incr. OS5yr P=0.01 2 individual studies showed survival benefit with PF(GSTTC ; GETTEC)

  18. Improved Complete Response Rate and Survival in Advanced Head and Neck Cancer After Three-Course Induction Therapy With 120-Hour 5-FU Infusion and Cisplatin MICHAEL ROONEY, MD,.t JULIE KISH, MD,JOHN JACOBS, MD.( JEANNIE KINZIE, MD,ARTHUR WEAVER, MD., JOHN CRISSMAN. MD. AND MUHYl AL-SARRAF. MD Cancer 55: 1 1 23- I 1 28. 1985.

  19. MACH-NC Collaborative Group:Effect of Chemotherapy on 5-Year Survival Meta-analyses of individual patient data from randomized trial thatrecruited patients from 1965 to 1993 PF induction conferred a 5% survival gain at 5-years CRT conferred an 8% survival improvement at 5-years CRT=chemoradiotherapy; PF=cisplatin+5-FU. Monnerat C, et al. Ann Oncol. 2002;13:995. [Review] Pignon JP, et al. Lancet. 2000;355:949.

  20. Change the schedule of ICT Change the approach of treatment SCCHNC HOW CAN WE IMPROVE THESE RESULTS?

  21. R EORTC 24971/TAX 323 - Study Design Induction CT + Locoregional RT Neck Dissection Surgery for Residual Disease TPF arm (n=177)  Docetaxel (75 mg/m²)  Cisplatin (75 mg/m²)  5-FU (750 mg/m²/dx5) Q 3 weeks x 4 cycles Inoperable SCCHN Stage 3-4. Radiotherapy (~70 Gy over 7 weeks) Follow up Stratification:1º tumor site Institution PF arm (n=181)  Cisplatin (100 mg/m²)  5-FU (1000 mg/m²/dx5) Q 3 weeks x 4 cycles Primary Objective:PFS Treatment arms were well balanced in baseline characteristics Remenar E, et al. ASCO 2006, abstract 5516. Bernier J, et al. ASCO 2006, abstract 5522.Vermorken JB, et al. ASCO 2004, abstract 5508.

  22. 100 90 80 70 60 50 40 30 20 10 0 EORTC 24971/TAX 323 Overall Survival Treatment PF TPF 0 6 12 18 24 30 36 42 48 54 60 66 72 (months) Remenar E, et al. ASCO 2006, abstract 5516. Bernier J, et al. ASCO 2006, abstract 5522.Vermorken JB, et al. ASCO 2004, abstract 5508.

  23. R TAX 324 - Study Design Induction CT CRT  Surgery N=538 Primary Objective:OS Stage III/IV Epidermoid carcinoma, no prior surgery, no hospitalization for COPD 1y PF arm (n=246)  Cisplatin (100 mg/m²/d1)  5-FU (1000 mg/m²/d 5) Q 3 weeks x 3 cycles Radiotherapy(70Gy d1-5) + WeeklyCarboplatin(AUC 1.5 7) Surgery is needed TPF arm (n=255)  Docetaxel (75 mg/m²)  Cisplatin (100 mg/m²d1)  5-FU (1000 mg/m²/d 4) Q 3 weeks x 3 cycles • Stratification: • Center • N status • Primary site Treatment arms were well balanced in baseline demographicand disease characteristics Posner RM, et al. ASCO 2006, abstract SPS24.

  24. TAX 324 - Study Design Primary Endpoint: Overall Survival 100 • TPF significantly improvedoverall survival vs PF • 30% reduction in mortality 90 80 70 60 TPF (n=255) Survival Probability (%) 50 PF (n=246) 40 2-Year OSTPF 67%PF 54% 3-Year OSTPF 62%PF 48% 30 Log-Rank p = .0058Hazard ratio = 0.70 20 0 10 42 Survival Time (months) 0 6 12 18 24 30 36 48 54 60 66 72 Posner RM, et al. ASCO 2006, abstract SPS24.

  25. 100 90 80 70 60 50 40 30 20 10 0 0 0 6 6 12 12 18 18 24 24 30 30 36 36 42 42 48 48 54 54 60 60 66 66 72 72 HNSCC: Taxotere in Locally-Advanced Disease Overall Survival TAX 32430% reduction in risk of death TAX 32329% reduction in risk of death TPF PF Survival Probability (%) TPF PF Survival Time (months) Survival Time (months) Posner et al. ASCO 2006. Remenaer et al., ASCO 2006

  26. R Phase III Trial PF ± Docetaxel  CRT vs CRT Study Design Primary endpoint phase III:TTF PF  3 cycles q 21 days • Cisplatin • Infusional 5-FU (N=440) CRT SCHNN Stage III, IV(locally advanced) Unresectable TPF  3 cycles q 21 days • Docetaxel • Cisplatin • Infusional 5-FU CRT Hitt R, et al. ASCO 2006, abstract 5515.

  27. Phase III Trial PF ± Docetaxel  CRT vs CRT EFFICACY p = 0.0080 Hitt R, et al. ASCO 2006, abstract 5515.

  28. Does the Complete Response to Induction Chemotherapy/CRT have the same benefit in survival ? Al Sarraf Cancer 1985

  29. OLD STANDARD GOLDSTANDARD CRT ICT/CRT CHEMORADIOTHERAPYHNC STANDARD TREATMENT

  30. CONCLUSIONS (1) • Hypopharyngeal SCC has a bad prognostic with conventional treatment • The objective of treatment can be : cure-quality of life • For Medical Oncologist Hypopharyngeal Cancer= SCCHN • To day is possible Larynx Preservation without damage OS • Induction chemotherapy is feasible in a set of the patients • Chemoradiotherapy can be a Radical Treatment

  31. CONCLUSIONS (2) • When is possible: Salvage Surgery is recommended • Now we have data about the superiority of TPF as ICT • Complete Response to TPF/CRT might be a parameter as overall survival • Induction TPF plus CRT might be the next standard • Selection of patients is the key for treatment selection • RESECTABLE////UNRESECTABLE TUMORS

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