Post on 14-Dec-2015
Neoadjuvant Chemotherapy in Neoadjuvant Chemotherapy in Locally Advanced Squamous Cell Locally Advanced Squamous Cell Cancer of Head and NeckCancer of Head and Neck
Mei Tang, MDMei Tang, MD
Head and Neck CancerHead and Neck Cancer
Worldwide Worldwide New cases : 644,000New cases : 644,000 Cancer deaths: 350,000Cancer deaths: 350,000 About 5% of all cancers About 5% of all cancers
Local Recurrence: 40% - 60%Local Recurrence: 40% - 60% Distant metastatic disease: 20 - 30%Distant metastatic disease: 20 - 30%
The Role of Concomitant The Role of Concomitant Chemotherapy in Locally Chemotherapy in Locally Advanced SCCHNAdvanced SCCHN
The Lancet March 18, 2000
MACH-NC 2000MACH-NC 2000
63 trials (10,741 patients)63 trials (10,741 patients) 1965 – 19931965 – 1993 Cancers of oropharynx, oral Cancers of oropharynx, oral
cavity, larynx, and hypopharynx cavity, larynx, and hypopharynx Many countries contributed to this Many countries contributed to this
reportreport
Timing of Timing of ChemotherapyChemotherapy Neoadjuvant/induction Neoadjuvant/induction
chemotherapychemotherapy
Concomitant chemotherapy Concomitant chemotherapy (chemoradiotherapy, CRT)(chemoradiotherapy, CRT)
Adjuvant chemotherapy Adjuvant chemotherapy
Concomitant chemoradiotherapy is Concomitant chemoradiotherapy is the current the current standard therapystandard therapy for for stage III and IV who do not stage III and IV who do not undergo surgeryundergo surgery
Induction Chemotherapy: an Induction Chemotherapy: an attractive optionattractive option
To allow the assessment of tumor To allow the assessment of tumor responseresponse
To select appropriate patient for To select appropriate patient for organ preservationorgan preservation
To improves local controlTo improves local control To reduce distant metastasesTo reduce distant metastases
Chemotherapy in Newly Diagnosed Chemotherapy in Newly Diagnosed vsvs Recurrent Recurrent Disease patientsDisease patients
Response RateResponse Rate
ChemotheraChemotherapypy
New DiagnosisNew Diagnosis RecurrenceRecurrence
DDP/BleoDDP/Bleo 71%71% 33%33%
DDP/Bleo/VinblDDP/Bleo/Vinbl 74%74% 45%45%
DDP/MTX/BleoDDP/MTX/Bleo 88%88% 25%25%
Bleo/MTX/VCRBleo/MTX/VCR 71%71% 43%43%
Evidence supporting induction Evidence supporting induction chemotherapychemotherapy
The VA trial No. 268 CT-RT vs Surg.-The VA trial No. 268 CT-RT vs Surg.-RT (P)RT (P)
The EORTC trials in early 1990s (PF)The EORTC trials in early 1990s (PF) Intergroup trial 91-11(PF)Intergroup trial 91-11(PF)
1.1. A higher organ preservation or as A higher organ preservation or as good as concomitant CRTgood as concomitant CRT
2.2. A lower rate of distant failure A lower rate of distant failure 3.3. A trend toward improved survival, A trend toward improved survival,
particularly in unresectable patientsparticularly in unresectable patients
Adding Taxanes into induction Adding Taxanes into induction regimen (TPF – RT)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,
Dosage in Chemo-Dosage in Chemo-regimensregimens
TPF (q3wk)TPF (q3wk) PF(q3wk)PF(q3wk)
Docetaxol Docetaxol (T)(T)
75 mg/m275 mg/m2 N/AN/A
Cisplatin (P)Cisplatin (P) 75 mg/m275 mg/m2 100 mg/m2100 mg/m2
5-FU (F)5-FU (F) 1000 mg 1000 mg /m2 day 1-4/m2 day 1-4
1000 mg/m2 1000 mg/m2 day 1-5day 1-5
Limitations of the Data Limitations of the Data
Trials between 1965-1993Trials between 1965-1993 Different chemotherapy regimens Different chemotherapy regimens
(drug/schedules)(drug/schedules) Platinum and 5-FU regimens are Platinum and 5-FU regimens are
associate with 5% survival benefit associate with 5% survival benefit at 5 yearsat 5 years
Response to chemotherapy was Response to chemotherapy was not taken into accountnot taken into account
5-FU/Cisplatin in Previously 5-FU/Cisplatin in Previously Untreated PatientsUntreated Patients
No. No.
PatientsPatientsResponseResponse
(%)(%)Complete Complete ResponseResponse
(%)(%)
RTOGRTOG 84’84’ 2323 9191 3939
RooneyRooney 85’85’ 6161 9393 5454
VALCSGVALCSG 91’91’ 166166 8585 3131
PaccagnellaPaccagnella 94’94’ 118118 8080 3131
AthanasiadisAthanasiadis 97’97’ 7171 8383 3232
Rationales of Induction Rationales of Induction ChemotherapyChemotherapy
1. There is increased 1. There is increased responsiveness in previously responsiveness in previously untreated patientsuntreated patients
2. Possible improvement in survival2. Possible improvement in survivalImprove locoregional controlImprove locoregional control
Decrease distant metastasesDecrease distant metastases
3. Surgical modification/organ 3. Surgical modification/organ preservationpreservation
TPF Improves PFS and OS When It Was Compared to PF in Induction
TFP has better local control but no significant benefit in control of distant disease comparing to PF .
OS PFS
Patient Selection Outside Patient Selection Outside Clinical TrialsClinical Trials
Young (55 yo)Young (55 yo) PS 0-1PS 0-1 No majoy comorbilities (RI, uncontrolled No majoy comorbilities (RI, uncontrolled
DM, recent heart attached..)DM, recent heart attached..) Large primary: T3 or T4Large primary: T3 or T4 Extensive LN involvement (N2b or Extensive LN involvement (N2b or
above)above) Good nutrition standard Good nutrition standard
Targeted Therapy in Targeted Therapy in SCCH-NCSCCH-NC Cetuximab-RT Cetuximab-RT vs.vs. RT: RT: PF PF vs.vs. PF + Cetuximab PF + Cetuximab
It seems safe and effective:It seems safe and effective: Carboplatin (AUC 2)/Taxol (135 Carboplatin (AUC 2)/Taxol (135
mg/m2)/Cetuximabmg/m2)/Cetuximab TPF/CetuximabTPF/Cetuximab TPF-RT+cetuximabTPF-RT+cetuximab
Targeted Therapy in Targeted Therapy in SCCH-NCSCCH-NC Everolimus: mTOR inhibitorEverolimus: mTOR inhibitor
Panitumumab + chemoPanitumumab + chemo
Nimotumumab (EGFR ab)Nimotumumab (EGFR ab)
Is it time to change treatment Is it time to change treatment paradigm?paradigm?
No direct comparisonNo direct comparison of induction of induction chemotherapy to concomitant chemotherapy to concomitant treatment using the newer treatment using the newer regimenregimen
Induction chemotherapy has no defined role in
definitive treatment strategies
SummarySummary
Chemotherapy has established role in Chemotherapy has established role in locally adv. SCCHN locally adv. SCCHN
TPF – CRT is an alternative treatment TPF – CRT is an alternative treatment options besides the standard options besides the standard concomitant chemoradiotherapy.concomitant chemoradiotherapy.
CRT, not RT after TPF. CarboplatinCRT, not RT after TPF. Carboplatin TPF is better than PF in induction. It is TPF is better than PF in induction. It is
possible but not proven that TPF-CRT possible but not proven that TPF-CRT is better than CRT with cisplatin. is better than CRT with cisplatin.
Dosage of Cisplatin in Dosage of Cisplatin in CRT CRT 80% of pts tolerated > or = 6 doses of 80% of pts tolerated > or = 6 doses of
30 mg/m2 weekly. Total: 180-210 mg 30 mg/m2 weekly. Total: 180-210 mg 50% of pts tolerated 100 mg/m2 X 2. 50% of pts tolerated 100 mg/m2 X 2.
Total: 200 mgTotal: 200 mg Weekly is flexibl. The goal is to Weekly is flexibl. The goal is to
continue XRT with delay or dose continue XRT with delay or dose reduction.reduction.
No G-3 or 4 renal toxicity in weekly No G-3 or 4 renal toxicity in weekly dose.dose.