Transcript Neo-adjuvant chemotherapy in Squamous cell carcinoma of head

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
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Local Recurrence: 40% - 60%
Distant metastatic disease: 20 - 30%
SCCHN
The Role of Concomitant
Chemotherapy in Locally
Advanced SCCHN
The Lancet March 18, 2000
MACH-NC 2000
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63 trials (10,741 patients)
1965 – 1993
Cancers of oropharynx, oral cavity,
larynx, and hypopharynx
Many countries contributed to this
report
Overall Survival Benefit of
Chemotherapy
Timing of Chemotherapy
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Neoadjuvant/induction chemotherapy
Concomitant chemotherapy
(chemoradiotherapy, CRT)
Adjuvant chemotherapy
Timing of Chemotherapy
Concomitant chemoradiotherapy is the
current standard therapy for
stage III and IV who do not undergo
surgery
Induction Chemotherapy: an
attractive option
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To allow the assessment of tumor
response
To select appropriate patient for organ
preservation
To improves local control
To reduce distant metastases
Chemotherapy in Newly Diagnosed vs Recurrent Disease
patients
Response Rate
Chemotherapy
New Diagnosis
Recurrence
DDP/Bleo
71%
33%
DDP/Bleo/Vinbl
74%
45%
DDP/MTX/Bleo
88%
25%
Bleo/MTX/VCR
71%
43%
Evidence supporting induction
chemotherapy
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1.
2.
3.
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
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,
Dosage in Chemoregimens
TPF (q3wk)
PF(q3wk)
Docetaxol (T)
75 mg/m2
N/A
Cisplatin (P)
75 mg/m2
100 mg/m2
5-FU (F)
1000 mg /m2
day 1-4
1000 mg/m2
day 1-5
Timing of Chemotherapy
Limitations of the Data
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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
5-FU/Cisplatin in Previously Untreated
Patients
No.
Patients
Response
(%)
Complete
Response
(%)
RTOG
84’
23
91
39
Rooney
85’
61
93
54
VALCSG
91’
166
85
31
Paccagnella
94’
118
80
31
Athanasiadis
97’
71
83
32
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
Patient Selection 1
Patient Selection 2
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 .
Patient Selection Outside
Clinical Trials
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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
Targeted Therapy in
SCCH-NC
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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
Targeted Therapy in
SCCH-NC
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Everolimus: mTOR inhibitor
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Panitumumab + chemo
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Nimotumumab (EGFR ab)
Is it time to change treatment
paradigm?
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No direct comparison of induction
chemotherapy to concomitant
treatment using the newer regimen
Induction chemotherapy has no defined role in
definitive treatment strategies
Summary
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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.
Dosage of Cisplatin in
CRT
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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
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