Journal Reading Nasopharyngeal Carcinoma: Current Treatment Options and Future Directions

JOURNAL READING

Nasopharyngeal carcinoma :
Current treatment options and
future directions

Tutors :
dr. Agus Sudarwi, Sp. THT-KL
dr. Tris Sudyartono, Sp. THT-KL
dr. Afif Zjauhari, Sp. THT-KL

Created by :
Joice Gunawan Putri (406138049)
Yuli Iskandar (406147016)
Linda Lestari (406147017)
KUDUS GOVERNMENT GENERAL HOSPITAL

MEDICAL FACULTY TARUMANAGARA
UNIVERSITY
PERIOD 20 OCTOBER – 22 NOVEMVER 2014 1

Nasopharyngeal Carcinoma (NPC)
A tumor arising from the

epithelial cells that cover the
surface and line the
nasopharynx.
2
Abstract
Radiation therapy (RT) +/- chemotherapy 
standard treatment for NPC with intensity-
modulated radiation therapy (IMRT)
New treatment options  targeted

monoclonal antibodies and small molecule
tyrosine kinase inhibitors are being studied
as well. 3
Epidemiology
0 less common in North America
0 most common in Southern China, southeast

Asia and North Africa
4
Classification
0 WHO  3 Histologic
Subtypes :
0 squamous-cell carcinoma
0 differentiated non-
keratinizing carcinoma
0 undifferentiated non-
keratinizing carcinoma
5
American Joint Committee on Cancer
staging system
– Stages I
– Stages II-A
– Stages II-B
– Stages III
– Stages IV-A
– Stages IV-B
– Stages IV-C
6
Etiology Factors
1. Environmental carcinogens
2. Genetic
3. EBV
7
8
Sign and Symptom
0 nasopharynx
0 Epistaxis
0 Nasal obstruction
0 Discharge
0 parapharyngeal space leads to
0 Tinnitus
0 deafness
0 involvement of cranial nerve leads to
0 Headache
0 Diplopia
0 facial pain
0 numbness.
9
Diagnosis
0 Narrow Band Imaging 
detection of early NPC
0 Positive Biopsy  defenitive

diagnosis
10
Treatment
• Radiotherapy  early stage lesions
• Chemorhadiotherapy  more advanced diseases
3D-CRT  precisely maps the location of the

tumor
Intensity-modulated radiation therapy (IMRT) is an
advanced form 3D-CRT and is the mainstay for the
treatment of NPC.
11
Tham et al. conducted a review of 195 patients with non-
metastatic NPC treated with IMRT and showed 3-years
12
Intensity-modulated radiation
therapy (IMRT)
Study N Time point LC RC PFS DMFS OS
Lee et al 87 4 94 % 98 % - 66 % 73 %
Memorial 74 3 91 % 93 % 67 % - 83 %
Sloan-
Kettering
Hospital
13
Chemoradiotherapy (CRT)+Adjuvant
Chemotherapy (AC)
Study N Time LC RC PFS DMSF OS

point
Radiation 68 2 93 % 89 % 93 % 85 % 80 %
Therapy
Oncology
group
(RTOG)
14
Arm 1  cisplatin & 5-
NRG Oncology
Fluorouracil (5-FU)
NRG-HN001 trial
is currently
randomizing NPC
patients into two
arms based on Arm 2 
gemcitabine and
EBV DNA paclitaxel
detection, both
arms are receiving
RT+AC
The primary objective of the study is to determine whether arm 2
has superiority over arm 1 regimen to determine PFS 15
Side effects of radiation
 Mucositis
 Loss of taste
 Xerostomia
 Dysphagia
 Trismus
 Eustachian tube dysfunction
 Cranial nerve palsy
 Carotid Stenosis
16
Radio RT + Induction Chemothe CRT
therapy VS induction chemother vs rapy CR VS
+ AC
Chemotherapy apy +CRT T
Relapse 42,7% 50,9% (-) (-) (-) (-)
free
surviva
l
OS No No 67,7% 94,1% (-) (-)
improvement improvement
PFS (-) (-) 59% 88%

FFS (-) (-) 84% 86%
Wei hu et al Paclitaxel + AC effective for locally advanced

NPC
Trials comparing RT vs
chemoradiotherapy
Treatment OS (%) PFS (%) No of
patients
Al-Sarraf et al RT 70 GY 46 24 69
RT + 3cycles cisplatin 76 69 78
Chan et al RT 66 GY 58,6 52 176
RT+ weekly cisplatin 70,3 60 174
Kwong et al RT 62.5-68GY 77 58 109
RT+uracil+tegafur+cisplatin+flu 87 69 110
orouracil/vinblastine
Zhang et al RT 70-74 GY 77 83 56
RT + 6cycles of oxaliplatin 100 96 59
Wee et al RT 70 GY 65 53 110
RT+ 3cycles of cisplatin 80 72 111
Lee et al RT 70 GY 64 53 176
RT+ 3cycles of cisplatin 68 62 172
Lee et al RT 70 GY 83 68 49
RT+ 3cycles of cisplatin+ 87 73 47
fluorouracil
Chen et al RT 70 GY 80 73 158
RT+7cycles of cisplatin 90 85 158
Cell
proliferation
apoptosis
mutation
Tumor-induced
angiogenesis
metastasis
• Several trials are ongoing to investigate the role of
monoclonal antibodies, tyrosine kinase inhibitors,
and Met (met proto-oncogenes; hepatocyte growth
factor receptor) inhibitors in NPC
Recent study
Proliferation in many types of
Met activation
cancer including NPC
SAIT301
Mediated by matrix metalloproteinase
• IL-6  promotes cell migration and invasion
Sun et al:
monoclonal antihuman IL-6R antibody 
↓proliferation, migration, invasion capabilities of
NPC cells
Cetuximab (monoclonal antibody)
• Binds EGFR • EGFR is overexpressed

in a variety of tumors,
• Blocks phosphorylation especially in head and
and activation of
neck cancer
receptor-associated
kinases
• Inhibits cell growth
• Induction of apoptosis
• Decreases matrix
metalloproteinase
Recent study
Cetuximab + IMRT
WITH OR WITHOUT
chemotherapy
EFFECTIVE
VEGF
Vascular endothelial
growth factor •Overexpressed in
67% of NPC
•Leads to tumor
metastasis
bevacizumab
Conclusion…
• IMRT is now frequently
used for NPC
• The treatment strategies
for NPC will continue to
change

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JOURNAL READING

KUDUS GOVERNMENT GENERAL HOSPITAL

A tumor arising from the

New treatment options  targeted

0 less common in North America

0 most common in Southern China, southeast

0 Positive Biopsy  defenitive

3D-CRT  precisely maps the location of the

Study N Time point LC RC PFS DMFS OS

Study N Time LC RC PFS DMSF OS

PFS (-) (-) 59% 88%

Wei hu et al Paclitaxel + AC effective for locally advanced

• IL-6  promotes cell migration and invasion

• Binds EGFR • EGFR is overexpressed

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