TRAITEMENT MEDICAL

DES
CANCERS DES VBEH

DR. ZOUBIRI 04/02/2017 PR. BOUNEDJAR

 TRAITEMENT MEDICAL
BUT: Améliorer la survie global
Augmenter la survie sans progression / maladie
Analgésie
Améliorer la qualité de vie

MOYENS:
Chimiothérapie
Radiothérapie
Soins de support (BSC)
 Avant essais cliniques
• Difficultés d’inclusion et de randomisation
• Phase I et II
• Perdus de vu
• Pas d’essais intéressants
• Conflit d’intérêt / Buzz
• Pc sombre, durée de SG réduite
 Chimiothérapie

But : Selon l’indication :

Adjuvante: Controversée dans les études (Essai PRODIGE 12)
Néo-adjuvante
Palliative

Drogues actives :
5FU, mitomycine, cisplatine, gemcitabine, oxalipltine...
 Protocoles actifs

- FU-CDDP
 5FU 800 mg/m2/j (1000 mg/m2/j à cure 2 si tox < 3) en perfusion continue de J1 à J5 ;
 CDDP 100 mg/m2 en perfusion de 1 h à J2 tous les 28 j.

- LV-5FU2-CDDP
 Cisplatine 50 mg/m2 en perfusion de 60 mn dans 250 ml de sérum physiologique au J1 du LV5FU2
 Puis acide folinique 200 mg/m2 (ou acide l-folinique 100 mg/m2) en 2 h dans 250 ml de sérum glucosé 5
% j1 et j2
 5FU 400 mg/m2 en 10 min dans 100 ml de G 5 % j1 et j2
 5FU 600 mg/m2 en perfusion continue de 22 h dans G 5 % j1 et j2 tous les 14 jours avec évaluation après
4 cures.

- Gemcitabine monothérapie :
 Gemcitabine 1000 mg/m² en perfusion de 30 min à J1, J8 et J15
 Reprise du cycle à J29
- Gemcitabine-oxaliplatine (GEMOX)
 Gemcitabine 1000 mg/m2 en perfusion de 10mg/m2/mn dans 250 ml de sérum physiologique a J1
 Oxaliplatine 100mg/m2 en perfusion de 2 heures dans 500 ml de sérum glucosé 5 % A J2
 tous les 14 jours avec évaluation après 4 cures

- Gemcitabine-cisplatine (GEMCIS)
 Gemcitabine 1000 mg/m2 en perfusion de 30 mn dans 250 ml de sérum physiologique
 Cisplatine 30 mg/m2 en bolus après la gemcitabine A J1, J8 et J15 (J1=J28)
 Evaluation toutes les 8 semaines

- ECF
 Epirubicine 50 mg/m² à J1 
 Cisplatine 60 mg/m² à J1 (avec hyperhydratation) 
 5-Fluorouracile 200 mg/m²/jour IV en continu 24 semaines
 Reprise du cycle à J22
- ECX 
 Epirubicine 50 mg/m² à J1 
 Cisplatine 60 mg/m² à J1 (précédé et suivi d'une hyperhydratation) 
 Capecitabine 1000 mg/m² 2 fois par jour de J1 à J14
 CT palliative Systémique
Revue de 100 essais disponibles : Randomisation?????
pas de preuve formelle d’une augmentation de la survie après CT par rapport au drainage biliaire seul

Protocoles RO RO SM SM Toxicité
Médiane Extrêmes Médiane Extrêmes
MonoCT(1) 10% 0-33% < 8mois 4.5-10
PolyCT avec FP 20% 0-43% <10 mois 5-14 Supérieure
FP+Cispl/oxali 20-30%
Gemci mono 20% 0-60% < mois 5-16 B.tolérance
Gemci + S.plat/cape 30-40% 9-53% 10 mois 4.5-15.4 Supérieure
FP+s.pla+/-Epirubi 19-43% 5-11
Gemcit+Cape/s.plat 10-50% 4.5-15.4
- 5FU, acide folinique +/- etoposide (FELV) : Un essai contrôlé randomisé : FELV augmentait la qualité de
vie et la survie par rapport aux soins de de façon non significative dans le sous groupe des patients atteints de
cancer biliaire, toxicité considérable (grade 3-4, 41%).
- GEMCITABINE > 5FU/XELODA.
- GEM+S.PLATINE > 5FU+S.PLATINE > GEMCITABINE. (1)
- Exemple : GEM-CDDP > GEM (2).
(1): Une revue systématique récente de 88 essais
(2): Les résultats préliminaires d’un essai de phase II randomisé multicentrique
- GEMOX (1):
 A l’avantage sur gemcitabine-cisplatine de ne pas nécessiter d’hyperhydratatation.
 Il est réalisable même en cas de dysfonction hépatique, et semble pouvoir apporter un bénéfice clinique même
chez les patients à l’état général altéré.
 moins efficace en cas d'adénocarcinome de la vésicule biliaire qu'en cas de cholangiocarcinome.
(1): deux essais de phase II multicentriques, français et international
- CapOX :
 actif en cas d’ADK de la vésicule biliaire ou cholangiocarcinome extra-hépatique.
 inactif en cas de cholnagiocarcinome intra-hépatique "périphérique".
 CT palliative régionale

- La CT ou la chimio-embolisation intra-artérielle hépatique :

puisque l’arbre biliaire est majoritairement vascularisé par
l’artère hépatique.

- Taux de réponse encourageants observés dans des études pilotes

durées de réponse courtes, difficulté de la technique.
 Radiothérapie
But : Selon indication, adjuvante ou palliative

Méthodes :
RT locale (de contact)
RT externe.

Doses : 40-60 Gy

Indications : Tumeur opérable : R1, R2 ou N+: RT ou RCC

 RT adjuvante : Essais : bénéfice de survie avec la RT administrée à la dose de 45 à 60 Gy
(les doses les plus fortes étant habituellement administrées en cas de marges positives),
seule ou associée à une RT peropératoire, notamment en cas de marges positives ou
d’envahissement ganglionnaire.
 RCT adjuvante : Essais non randomisés (par exemple, 40 Gy plus 5FU bolus) ont suggéré
un bénéfice de survie, notamment en cas de marges positives (R1, mais non R2). Pas de
bénéfice de la RCT adjuvante sur la RT adjuvante seule.

 RT et RCT palliatives : Résultats d’essais :

 Pas de bénéfice dans les cancers biliaires localement avancés.
 Efficacité supérieure de la RCT en cas d’irradiation à forte dose (> 55 Gy).
 Des résultats encourageants avec une RT conformationnelle associée à une CT régionale.
 Des réponses objectives tumorales à la RT ou à la RCT peuvent rendre secondairement
résécables.
 La RT ou RCT contrôle symptomatique (décompression biliaire, douleur, perméabilité
prothétique).
 Après essais cliniques
• Difficultés d’inclusion et de randomisation
• Phase I et II
• Perdus de vu
• Pas d’essais intéressants
• Conflit d’intérêt / Buzz
• Pc sombre, durée de SG réduite
 Traitements néo-adjuvant
• Néo-adjuvant
• Cas rapportés de patients rendus résécables par
une radio-chimiothérapie

• Pas d’essai de phase III

 Drainage biliaire palliatif
• Prothèses :
• Si survie > 6 mois (tumeur < 3 cm, pas de métastases hépatiques)
Métallique (+ coût/efficace); unilatérale et si nécessaire bilatérale
Changement systématique de prothèse plastique tous les 3 mois
• Si survie < 6 mois : plastique
• Prothèses couvertes :
Perméabilité plus longue : non démontrée
Prévention de l’obstruction prothétique : non
• Si échec : drainage externe percutané
 Radiothérapie et Radio-
chimiothérapie palliatives
• Tumeurs localement avancées (non métastatiques)
• RT, RT + curiethérapie, RCT : bénéfice non démontré
• RCT + efficace si > 55 Gy
• Parfois : réponse objective  résection secondaire
• Contrôle local tumoral et symptomatique : décompression
biliaire, antalgie

Int J Radiat Oncol Biol Phys 1994;29:855

Int J Radiat Oncol Biol Phys 1996;34:767
Int J Radiat Oncol Biol Phys 1996;34:445
 CT palliative : Phases II
Exemple : Fluoropyrimidine-platine  anthracycline
RO SSP SG
Essai Schéma Patients
(%) (mois) (mois)
Kobayashi, 2006 5FU, cisplatine 42 43 3.5 7.4
Ducreux, 1998 5FU, cisplatine 25 24 - 10.0
Ducreux, 2005 (IIR) 5FU, LV, cisplatine 29 19 3.3 8.0
Taïeb, 2002 5FU, LV, cisplatine 29 34 6.5 9.5
Sanz-Altamira, 1998 5FU, LV, carboplatine 14 21 - 5.0
Kim, 2003 Cap, cisplatine 42 21 3.7 9.1
Nehls, 2002 5FU, LV, oxaliplatine 16 19 4.1 9.5
Glover, 2005 (A) Cap, oxaliplatine 21 19 - -
Nehls, 2006 (A) Cap, oxaliplatine 65 17 - -
Rao, 2005 (III) 5FU, EPI, cisplatine (ECF) 27 19 5.2 9.0
Ellis, 1995 5FU, EPI, cisplatine (ECF) 25 40 - 11.0
Lee, 2004 5FU, EPI, cisplatine (ECF) 20 10 - 5.0
Park, 2005 UFT, LV, EPI, cisplatine 40 22 3.7 7.8
Park, 2006 Cap, EPI, cisplatine (ECX) 43 40 5.2 8.0
Patt, 2001 5FU, doxo, cisplatine, IFN (PIAF) 41 21 - 14.0
 Chimiothérapie palliative : 2009
Premières études de phase III
• Tumeurs localement avancées et métastatiques
• Valle JW (# 4503 JCO 2009, 27, 202S) ABC 02
• UK N = 410
– gemcitabine J1,J8,J15 /28j versus
– gemcitabine 1000mg/m2 + cisplatine 25mg/m2 J1, J8, / 21 J
• Survie globale : 11,7 vs 8,2 mois p = 0,002 HR 0,68 (0,53-0,86)
 Tumeurs localement avancées et métastatiques
Essai ABC-02 : gemcitabine + cisplatine
Survie sans progression Survie globale
1,00 1,00
Gemcitabine + cisplatine Gemcitabine + cisplatine
0,75 Gemcitabine 0,75 Gemcitabine
Survie (%)

0,50 0,50

0,25 0,25

0 0
0 200 400 600 800 1 000 0 200 400 600 800 1 000
Suivi (jours) Suivi (jours)
Gem Gem + Cis Bras de traitement Gem Gem + Cis
Bras de traitement

204 206 Nombre de patients 204 206

Nombre de patients

6,5 8,4 SG médiane (mois) 8,3 11,7

SSP médiane (mois)
p 0,002
p 0,003
Gemcitabine +cisplatine : nouveau standard de traitement des 0,70
Hazard-ratio (IC )
cancers
(0,54-0,89) 95
Hazard-ratio (IC ) 0,72 (0,57-0,90)
des voies biliaires avancés
95

ASCO 2009 - D’après Valle JW et al., abstract 4503 actualisé

 Traitement palliatif
REFERENCE (grade B-C) :
Drainage biliaire endoscopique et/ou percutané (prothèse plutôt que drain)
Drainage chirurgical si échec et espérance de vie > 6 mois, ou si tumeur trouvée
non résécable lors d’une laparoscopie ou laparotomie

Puis
Puis selon
selon PS
PS

PS
PS >> 22 PS  22
PS

Métastatique
Métastatique Localement
Localement avancé
avancé

Abstention Chimiothérapie
Chimiothérapie Chimiothérapie
Chimiothérapie
Abstention
(grade
(grade AA :: àà confirmer
confirmer par
par (GEM-Cis)
(GEM-Cis)
publication
publication écrite)
écrite) Ou
Ou
Gemcitabine RCT
RCT
Gemcitabine -- cisplatine
cisplatine
Pistes pour l’avenir ?
1- Thérapies ciblées
• Cetuximab : phase II randomisée en en cours en association au
GEMOX (Bingo)
• Erlotinib
• Lapatinib

2- Traitement de seconde ligne ?

SG---, PS, Fonction hépatique
Les cancers digestifs
à l’ESMO 2015
Digestive cancers at the ESMO congress 2015
Cancers du pancréas et des voies biliaires
Étude AFUGEM : une synergie du nab-paclitaxel démontrée avec le 5-FU (Bachet JB
et al., abstr. 2355)

J.B. Bachet a présenté, au nom du GERCOR, les premiers résultats de l’étude de phase
II randomisée AFUGEM comparant l’association nab-paclitaxel + gemcitabine (Nab-
Gem) à l’association nab-paclitaxel + LV5FU2 simplifié (Nab-FU) chez des patients
porteurs d’un adénocarcinome du pancréas métastatique.
À 4 mois, le taux de SSP (objectif principal de l’étude) était de 55,3 % dans le bras Nab-
Gem et de 55,6 % dans le bras Nab-FU. La SG était de 9,2 mois dans le bras Nab-Gem
et de 11,6 mois dans le bras Nab-FU. Les profils de tolérance ont été comparables dans
les 2 bras. Le schéma nab-paclitaxel + LV5FU2 simplifié a donc atteint son objectif, et
pourrait être évalué dans le cadre d’une étude de phase III afin de mieux déterminer son
intérêt potentiel dans la prise en charge des cancers du pancréas métastatiques.
L’immunothérapie fonctionne aussi dans les cancers des
voies biliaires
(Bang YJ et al., abstr. 525)

Un peu plus de 40 % des tumeurs des voies biliaires surexpriment PD-L1. L’étude
de phase Ib KEYNOTE-028 multicohortes avec le pembrolizumab, anticorps
monoclonal anti-PD-L1, a permis d’obtenir, chez 24 patients porteurs d’une
tumeur des voies biliaires prétraités (parfois lourdement), 17 % de réponses
partielles, un contrôle de la maladie chez 34,8 % des
patients, et des durées de réponse particulièrement intéressantes (de plus de 5,4
mois à plus de 9,3 mois).
Quatre (17 %) des 24 patients inclus ont présenté des effets indésirables sévères.
Enfin un traitement efficace et globalement bien toléré ! À suivre…
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NCCN Guidelines Version 2.2016 NCCN Guidelines

Index Hepatobiliary Cancers Table of
Gallbladder Cancer Contents
Discussion
PRESENTATION POSTOPERATIV PRIMARY TREATMENT
E WORKUP

Cholecystectomyb See Adjuvant

+ en bloc hepatic resection Treatment
Resectableb and
+ lymphadenectomy Surveillance
± bile duct excision (GALL-5)
• Intraoperative
staging CT/MRI
Incidental
• Frozen section of with IV
finding
gallbladder contrast,
at
• Consider extended chest Options:c
surgery
CT • Gemcitabine/cisplatin combination therapyd (category 1)
cholecystectomya • Fluoropyrimidine-based or other gemcitabine-based
Unresectable chemotherapy regimend
• Fluoropyrimidine chemoradiatione
• Clinical trial
• Best supportive care

Incidental
finding on See (GALL-2)
pathologic
review

aDepends on expertise of surgeon and/or resectability. If resectability not clear, close incision.
bSee Principles of Surgery (GALL-A).
cOrder does not indicate preference. The choice of treatment modality may depend on extent/location of disease and institutional capabilities.
dA phase III trial supporting gemcitabine/cisplatin has been reported for patients with advanced or metastatic billiary tract cancer. Valle JW, Wasan HS, Palmer DD, et al.
Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Eng J Med 2010;362:1273-1281. Clinical trial participation is encouraged. There are phase II
trials that support the following combinations: gemcitabine/oxaliplatin, gemcitabine/capecitabine, capecitabine/cisplatin, capecitabine/oxaliplatin,
5-fluorouracil/oxaliplatin, 5-fluorouracil/cisplatin and the single agents gemcitabine, capecitabine, and 5-fluorouracil in the unresectable or metastatic setting.
(Hezel AF and Zhu AX. Systemic therapy for biliary tract cancers. Oncologist 2008;13:415-423).
eThere are limited clinical trial data to define a standard regimen or definitive benefit. Clinical trial participation is encouraged. (Macdonald OK, Crane CH. Palliative and
postoperative radiotherapy in biliary tract cancer. Surg Oncol Clin N Am 2002;11(4):941-954).
Other Clinical
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged. Presentations
(See GALL-
Version 2.2016 06/27/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. 3)and (GALL- GALL-1
4)
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NCCN Guidelines Version 2.2016 NCCN Guidelines

Index Hepatobiliary Cancers Table of
Gallbladder Cancer Contents
Discussion
PRESENTATION POSTOPERATIV PRIMARY TREATMENT
E WORKUPf

T1a See Adjuvant

Treatment
(with negative Observe and Surveillance
margins) (GALL-5)

Incidental See Adjuvant

Hepatic resectionb Treatment
finding on and
pathologic Resectableb + lymphadenectomy
Surveillance
reviewf ± bile duct excision (GALL-5)
• CT/MRI with IV
contrast,
T1b or chest CT
greater • Consider
staging Options:c
laparoscopyg • Gemcitabine/cisplatin combination therapyd (category 1)
• Fluoropyrimidine-based or other gemcitabine-based
Unresectable chemotherapy regimend
• Fluoropyrimidine chemoradiatione
• Clinical trial
• Best supportive care

bSee Principles of Surgery (GALL-A).

cOrder does not indicate preference. The choice of treatment modality may depend on extent/location of disease and institutional capabilities.
dA phase III trial supporting gemcitabine/cisplatin has been reported for patients with advanced or metastatic billiary tract cancer. Valle JW, Wasan HS, Palmer DD, et al
Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Eng J Med 2010;362:1273-1281. Clinical trial participation is encouraged. There are phase II
trials that support the following combinations: gemcitabine/oxaliplatin, gemcitabine/capecitabine, capecitabine/cisplatin, capecitabine/oxaliplatin,
5-fluorouracil/oxaliplatin, 5-fluorouracil/cisplatin and the single agents gemcitabine, capecitabine, and 5-fluorouracil in the unresectable or metastatic setting.
(Hezel AF and Zhu AX. Systemic therapy for biliary tract cancers. Oncologist 2008;13:415-423).
eThere are limited clinical trial data to define a standard regimen or definitive benefit. Clinical trial participation is encouraged. (Macdonald OK, Crane CH. Palliative and
postoperative radiotherapy in biliary tract cancer. Surg Oncol Clin N Am 2002;11:941-954).
fConsider multidisciplinary review.
gButte JM, Gonen M, Allen PJ, et al. The role of laparoscopic staging in patients with incidental gallbladder cancer. HPB (Oxford) 2011;13:463-472.

Note: All recommendations are category 2A unless otherwise indicated.

Other Clinical
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Presentations
(See GALL-3) GALL-2
Version 2.2016 06/27/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. and (GALL-4)
Printed by ferimine onco on 2/3/2017 9:35:36 AM. For personal use only. Not approved for distribution. Copyright © 2017 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 2.2016 NCCN Guidelines

Index Hepatobiliary Cancers Table of
Gallbladder Cancer Contents
Discussion
PRESENTATION WORKUP PRIMARY TREATMENT

See Adjuvant
Cholecystectomyb Treatment
• H&P Resectableb and
+ en bloc hepatic resection Surveillance
• CT/MRI with IV (GALL-5)
+ lymphadenectomy ± bile duct excision
contrast
• Liver function tests
(LFTs)
Mass on • Chest CT
• Surgical
imaging consultation
• Assessment of Options:c
• Gemcitabine/cisplatin combination therapyd (category 1)
hepatic reserve
• Consider CEAh • Fluoropyrimidine-based or other gemcitabine-based
• Consider CA Unresectable Biopsy chemotherapy regimend
• Fluoropyrimidine chemoradiatione
19-9h
• Consider staging • Clinical trial
• Best supportive care
laparoscopy

bSee Principles of Surgery (GALL-A).

cOrder does not indicate preference. The choice of treatment modality may depend on extent/location of disease and institutional capabilities.
dA phase III trial supporting gemcitabine/cisplatin has been reported for patients with advanced or metastatic billiary tract cancer. Valle JW, Wasan HS, Palmer DD, et al.
Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Eng J Med 2010;362:1273-1281. Clinical trial participation is encouraged. There are phase II
trials that support the following combinations: gemcitabine/oxaliplatin, gemcitabine/capecitabine, capecitabine/cisplatin, capecitabine/oxaliplatin,
5-fluorouracil/oxaliplatin, 5-fluorouracil/cisplatin and the single agents gemcitabine, capecitabine, and 5-fluorouracil in the unresectable or metastatic setting.
(Hezel AF and Zhu AX. Systemic therapy for biliary tract cancers. Oncologist 2008;13:415-423)
eThere are limited clinical trial data to define a standard regimen or definitive benefit. Clinical trial participation is encouraged. (Macdonald OK, Crane CH.

Palliative and
postoperative radiotherapy in biliary tract cancer. Surg Oncol Clin N Am 2002;11:941-954).
hCEA and CA 19-9 are baseline tests and should not be done to confirm diagnosis.
Note: All recommendations are category 2A unless otherwise indicated.
Other Clinical Presentations
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
(See GALL-1), (GALL-2),
and (GALL-4)
Version 2.2016 06/27/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
GALL-3
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NCCN Guidelines Version 2.2016 NCCN Guidelines

Index Hepatobiliary Cancers Table of
Gallbladder Cancer Contents
Discussion
PRESENTATION WORKUP PRIMARY TREATMENT
• Consider preoperative biliary drainage See Adjuvant
• H&P • Cholecystectomyb Treatment
• LFTs Resectableb + en bloc hepatic resection and
• Chest CT + lymphadenectomy Surveillance
• CT/MRI with IV contrast + bile duct excision (GALL-5)
Jaundice • Cholangiographyi
• Surgical consultationj Options:c
• Consider CEAh • Biliary drainagek
• Consider CA 19-9h • Gemcitabine/cisplatin combination therapyd (category 1)
• Consider staging Unresectable Biopsy • Other gemcitabine-based or fluoropyrimidine-based
laparoscopy chemotherapy regimend
• Fluoropyrimidine chemoradiatione
• Clinical trial
• Best supportive care

Options:c
• Biliary drainagek
Metastatic disease
• Gemcitabine/cisplatin combination therapyd (category 1)
• Other gemcitabine-based or fluoropyrimidine-based
bSee Principles of Surgery (GALL-A).
chemotherapy regimend
Clinicaland
cOrder does not indicate preference. The choice of treatment modality may depend on extent/location of• disease trial
institutional capabilities.
• Best
dA phase III trial supporting gemcitabine/cisplatin has been reported for patients with advanced or metastatic supportive
billiary care
tract cancer. Valle JW, Wasan HS, Palmer DD, et al. Cisplatin
plus gemcitabine versus gemcitabine for biliary tract cancer. N Eng J Med 2010;362:1273-1281. Clinical trial participation is encouraged. There are phase II
trials that support the following combinations: gemcitabine/oxaliplatin, gemcitabine/capecitabine, capecitabine/cisplatin, capecitabine/oxaliplatin,
5-fluorouracil/oxaliplatin, 5-fluorouracil/cisplatin and the single agents gemcitabine, capecitabine, and 5-fluorouracil in the unresectable or metastatic setting.
(Hezel AF and Zhu AX. Systemic therapy for biliary tract cancers. Oncologist 2008;13:415-423).
eThere are limited clinical trial data to define a standard regimen or definitive benefit. Clinical trial participation is encouraged. (Macdonald OK, Crane CH.
Palliative and
ostoperative radiotherapy in biliary tract cancer. Surg Oncol Clin N Am 2002;11:941-954).
hCEA and CA 19-9 are baseline tests and should not be done to confirm diagnosis.
iMagnetic resonance cholangiopancreatography (MRCP) is preferred. Endoscopic retrograde cholangiopancreatography/percutaneous transhepatic cholangiography
(ERCP/PTC) are used more for therapeutic intervention.
jkConsult with a multidisciplinary team.
Consider biliary drainage for patients with jaundice prior to instituting chemotherapy. Consider baseline CA 19-9 after biliary decompression.
Other Clinical
Note: All recommendations are category 2A unless otherwise indicated.
Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.
Presentations
Version 2.2016 06/27/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. See (GALL-2) GALL-4
and (GALL-3)
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NCCN Guidelines Version 2.2016 NCCN Guidelines

Index Hepatobiliary Cancers Table of
Gallbladder Cancer Contents
Discussion
ADJUVANT SURVEILLANCEn
TREATMENTl

For relapse, see Workup

Consider Consider of the following initial
fluoropyrimidine imaging every Clinical presentations:
chemoradiation 6 mo for 2 y
Mass on imaging
(except T1a or T1b, N0)e,l if clinically
(See GALL-3)
Post or or
indicated, then
Jaundice
(See
resection Fluoropyrimidine or annually up to 5 y GALL-4)
gemcitabine or
chemotherapy Metastases
regimenl,m Consider CEA and (See GALL-4)
or CA 19-9 as clinically
Observe indicated

eThere are limited clinical trial data to define a standard regimen or definitive benefit. Clinical trial participation is encouraged. (Macdonald OK, Crane CH. Palliative and
postoperative radiotherapy in biliary tract cancer. Surg Oncol Clin N Am 2002;11:941-954).
lAdjuvant chemotherapy or chemoradiation has been associated with survival benefit in patients with biliary tract cancer (BTC), especially in patients with lymph node-
positive disease (Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systemic review and meta-analysis.
J Clin Oncol 2012;30:1934-1940).
mThere are no randomized phase III clinical trial data to support a standard adjuvant regimen. Clinical trial participation is encouraged. Single-agent fluoropyrimidine
or gemcitabine is generally recommended in the adjuvant setting.
nThere are no data to support surveillance. There should be a patient/physician discussion regarding appropriate follow-up schedules/imaging.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 2.2016 06/27/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®.
GALL-5
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NCCN Guidelines Version 2.2016 NCCN Guidelines

Index Hepatobiliary Cancers Table of
Extrahepatic Contents
Discussion
PRESENTATION
Cholangiocarcinoma
WORKUP PRIMARY TREATMENT
• Biliary drainage,e
if indicated Optionsg:
• Biopsyc • Gemcitabine/cisplatin combination therapyh
(only after (category 1)
Unresectablec determining • Clinical trial
transplant • Fluoropyrimidine-based or other
status) gemcitabine-based chemotherapy regimenh
• H&P • Consider • Fluoropyrimidine chemoradiationi
• CT/MRI (assess for referral • Supportive care
vascular invasion) • to
Surgical
• Pain with IV contrast transplant
• Jaundice explorationf
• Chest CT • center
Consider Unresectable, see above
• Abnormal • Cholangiographya
laparoscopic
LFTs • Consider CEAb Resectabled See Adjuvant
staging
• Obstruction or • Consider CA 19-9b • Consider Treatment and
abnormality on • LFTs
Resectabled Resectiond Surveillance
preoperative
imaging • Consider endoscopic (EXTRA-2)
biliary drainage
ultrasound (EUS) after
Optionsg:
surgical consultation • Gemcitabine/cisplatin combination therapyh
• Biliary drainage, (category 1)
Metastatic • Clinical trial
if indicated • Fluoropyrimidine-based or other
• Biopsy
disease gemcitabine-based chemotherapy regimenh
• Supportive care
aNoninvasive cholangiography with cross-sectional imaging.
bCEA and CA 19-9 are baseline tests and should not be done to confirm diagnosis.
cBefore biopsy, evaluate if patient is a resection or transplant candidate. If patient is a potential transplant candidate, consider referral to transplant center before biopsy.
dSee Principles of Surgery (EXTRA-A).
eConsider biliary drainage for patients with jaundice prior to instituting chemotherapy. Consider baseline CA 19-9 after biliary decompression.
fSurgery may be performed when index of suspicion is high; biopsy not required.
gOrder does not indicate preference. The choice of treatment modality may depend on extent/location of disease and institutional capabilities.
hA recent phase III trial supporting gemcitabine/cisplatin has been reported for patients with advanced or metastatic biliary tract cancer. (Valle JW, Wasan HS, Palmer
DD, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Eng J Med 2010;362:1273-1281) Clinical trial participation is encouraged. There are
phase II trials that support the following combinations: gemcitabine/oxaliplatin, gemcitabine/capecitabine, capecitabine/cisplatin, capecitabine/oxaliplatin,
5-fluorouracil/oxaliplatin, 5-fluorouracil/cisplatin, and the single agents gemcitabine, capecitabine, and 5-fluorouracil in the unresectable or metastatic setting.
(Hezel AF and Zhu AX. Systemic therapy for biliary tract cancers. Oncologist 2008;13:415-423).
iThere are limited clinical trial data to define a standard regimen or definitive benefit. Clinical trial participation is encouraged. (Macdonald OK, Crane CH. Palliative and
postoperative radiotherapy in biliary tract cancer. Surg Oncol Clin N Am 2002;11:941-954).

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 2.2016 06/27/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. EXTRA-1
Printed by ferimine onco on 2/3/2017 9:35:36 AM. For personal use only. Not approved for distribution. Copyright © 2017 National Comprehensive Cancer Network, Inc., All Rights Reserved.

NCCN Guidelines Version 2.2016 NCCN Guidelines

Index Hepatobiliary Cancers Table of
Extrahepatic Contents
Cholangiocarcinoma Discussion
ADJUVANT TREATMENTk SURVEILLANCE

Observe
or
Resected, negative margin (R0), Fluorop
Negative regional nodes yrimidin
or e
Carcinoma in situ at chemor
margin adiationi

Post or Consider imaging every

resection Fluoropyrimidine-based or 6 mo for 2 yn
status gemcitabine-based chemotherapyl as clinically indicated
Consider
or fluoropyrimidine
chemoradiation i
Resected, positive margin (R1)j Clinical trial
followed by additional
or fluoropyrimidine-based or
Resected gross residual gemcitabine-based chemotherapy
disease (R2)j or
or Fluoropyrimidine-based or
Positive regional nodes gemcitabine-based chemotherapy
for positive regional lymph nodesm

iThere are limited clinical trial data to define a standard regimen or definitive benefit. Clinical trial participation is encouraged. (Macdonald OK, Crane CH. Palliative
and postoperative radiotherapy in biliary tract cancer. Surg Oncol Clin N Am 2002;11:941-954).
jR1 or R2 resections should be evaluated by a multidisciplinary team.
kAdjuvant chemotherapy or chemoradiation has been associated with survival benefit in patients with biliary tract cancers, especially in patients with lymph node-
positive disease (Horgan AM, Amir E, Walter T, Knox JJ. Adjuvant therapy in the treatment of biliary tract cancer: a systemic review and meta-analysis. J Clin Oncol
2012;30:1934-1940).
lThere are limited clinical trial data to define a standard regimen. Clinical trial participation is encouraged.
mThere are no randomized phase III clinical trial data to support a standard adjuvant regimen. Clinical trial participation is encouraged. There are phase II trials that
support the following combinations: gemcitabine/cisplatin, gemcitabine/oxaliplatin, gemcitabine/capecitabine, capecitabine/cisplatin, capecitabine/oxaliplatin,
5-fluorouracil/oxaliplatin, 5-fluorouracil/cisplatin, and the single agents gemcitabine, capecitabine, and 5-fluorouracil in the unresectable or metastatic setting.
(Hezel AF and Zhu AX. Systemic therapy for biliary tract cancers. Oncologist 2008;13:415-423).
nThere are no data to support aggressive surveillance. There should be a patient/physician discussion regarding appropriate follow-up schedules/imaging.

Note: All recommendations are category 2A unless otherwise indicated.

Clinical Trials: NCCN believes that the best management of any cancer patient is in a clinical trial. Participation in clinical trials is especially encouraged.

Version 2.2016 06/27/16 © National Comprehensive Cancer Network, Inc. 2016, All rights reserved. The NCCN Guidelines® and this illustration may not be reproduced in any form without the express written permission of NCCN®. EXTRA-2
 CONCLUSION
Prise en charge multidisciplinaire diagnostique
thérapeutique


Traitement de choix Chirurgie

TRAITEMENT PALIATIF/ A FIN D’AMELIORER LA QUALITE DE VIE/ +++++++

Soins de support (Morphiniques …)
Gestion des effets secondaires (réduction de doses, PS,…)

L’amélioration de la survie passe par la nécessité d’une

chirurgie d’exérèse radicale qui doit primer sur
l’obtention d’une régression rapide de l’ictère
Intérêt

RCP