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Neoadjuvant Chemotherapy in Locally Advanced Squamous Cell Cancer of Head and Neck

Neoadjuvant Chemotherapy in Locally Advanced Squamous Cell Cancer of Head and Neck. Mei Tang, MD. Head and Neck Cancer. Worldwide New cases : 644,000 Cancer deaths: 350,000 About 5% of all cancers Local Recurrence: 40% - 60% Distant metastatic disease: 20 - 30%. SCCHN.

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Neoadjuvant Chemotherapy in Locally Advanced Squamous Cell Cancer of Head and Neck

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  1. Neoadjuvant Chemotherapy in Locally Advanced Squamous Cell Cancer of Head and Neck Mei Tang, MD

  2. Head and Neck Cancer Worldwide • New cases : 644,000 • Cancer deaths: 350,000 • About 5% of all cancers • Local Recurrence: 40% - 60% • Distant metastatic disease: 20 - 30%

  3. SCCHN

  4. The Role of Concomitant Chemotherapy in Locally Advanced SCCHN The Lancet March 18, 2000

  5. MACH-NC 2000 • 63 trials (10,741 patients) • 1965 – 1993 • Cancers of oropharynx, oral cavity, larynx, and hypopharynx • Many countries contributed to this report

  6. Overall Survival Benefit of Chemotherapy

  7. Timing of Chemotherapy • Neoadjuvant/induction chemotherapy • Concomitant chemotherapy (chemoradiotherapy, CRT) • Adjuvant chemotherapy

  8. Timing of Chemotherapy

  9. Concomitant chemoradiotherapy is the current standard therapy for stage III and IV who do not undergo surgery

  10. Induction Chemotherapy: an attractive option • To allow the assessment of tumor response • To select appropriate patient for organ preservation • To improves local control • To reduce distant metastases

  11. Chemotherapy in Newly Diagnosed vs Recurrent Disease patients

  12. Evidence supporting induction chemotherapy • The VA trial No. 268 CT-RT vs Surg.-RT (P) • The EORTC trials in early 1990s (PF) • Intergroup trial 91-11(PF) • A higher organ preservation or as good as concomitant CRT • A lower rate of distant failure • A trend toward improved survival, particularly in unresectable patients

  13. Adding Taxanes into induction regimen (TPF – RT) High complete response rate: 80-100% Local failure rate: 31% Distant failure rate: 6% Toxicity: Less nausea, mucositis, G-3 hearing loss, trombocytopenia and treatment related death. Higher neutropenic fever,

  14. Dosage in Chemo-regimens

  15. Timing of Chemotherapy

  16. Limitations of the Data • Trials between 1965-1993 • Different chemotherapy regimens (drug/schedules) • Platinum and 5-FU regimens are associate with 5% survival benefit at 5 years • Response to chemotherapy was not taken into account

  17. 5-FU/Cisplatin in Previously Untreated Patients

  18. Rationales of Induction Chemotherapy 1. There is increased responsiveness in previously untreated patients 2. Possible improvement in survival Improve locoregional control Decrease distant metastases 3. Surgical modification/organ preservation

  19. Patient Selection 1

  20. Patient Selection 2

  21. TPF Improves PFS and OS When It Was Compared to PF in Induction OS PFS TFP has better local control but no significant benefit in control of distant disease comparing to PF .

  22. Patient Selection Outside Clinical Trials • Young (55 yo) • PS 0-1 • No majoy comorbilities (RI, uncontrolled DM, recent heart attached..) • Large primary: T3 or T4 • Extensive LN involvement (N2b or above) • Good nutrition standard

  23. Targeted Therapy in SCCH-NC • Cetuximab-RT vs. RT: • PF vs. PF + Cetuximab It seems safe and effective: • Carboplatin (AUC 2)/Taxol (135 mg/m2)/Cetuximab • TPF/Cetuximab • TPF-RT+cetuximab

  24. Targeted Therapy in SCCH-NC • Everolimus: mTOR inhibitor • Panitumumab + chemo • Nimotumumab (EGFR ab)

  25. Is it time to change treatment paradigm? • No direct comparison of induction chemotherapy to concomitant treatment using the newer regimen Induction chemotherapy has no defined role in definitive treatment strategies

  26. Summary • Chemotherapy has established role in locally adv. SCCHN • TPF – CRT is an alternative treatment options besides the standard concomitant chemoradiotherapy. • CRT, not RT after TPF. Carboplatin • TPF is better than PF in induction. It is possible but not proven that TPF-CRT is better than CRT with cisplatin.

  27. Dosage of Cisplatin in CRT • 80% of pts tolerated > or = 6 doses of 30 mg/m2 weekly. Total: 180-210 mg • 50% of pts tolerated 100 mg/m2 X 2. Total: 200 mg • Weekly is flexibl. The goal is to continue XRT with delay or dose reduction. • No G-3 or 4 renal toxicity in weekly dose.

  28. SCCH-N in GBMC 2009 Total 238 cases of head neck cancer Eighty cases of cancers in oral cavity, oropharynx, larynx and hypopharynx Stage I: 22 Stage II: 9 Stage III: 14 Stage IV: 28 Unknown or Stage 0: 7

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