Chimioterapia in

cancerul colorectal
Dr Cainap Calin
Martie 2015

Chimioterapia - indicatii?
ADJUVANT

NEOADJUVANT

METASTATIC

CHIMIOTERAPIA ADJUVANTA

Chimioterapia adjuvanta indicatii

Chimioterapia adjuvanta indicatii

Std II high risk

Std III

5% (5FU)

10-15% (5FU) + 5% (LO

Std II high risk

Excizie sub 12 ggl (std II N=14 ggl)
G3
Ocluzie / perforatie
Invazie L,V, perineurala
ACE crescut persistent postoperator (ACE si CA 19-9 crescuti
preoperator pronostic negativ)

Std II high risk

Status MMR (mismatch repairs) la pacientii sub 70 de ani
MMR H / MSI 10-15% din std II nu beneficiaza de aportul chimioterapiei
adjuvante
(STATUSUL NU INTERESEAZA LA PACIENTII CU STD III)
JCO 2010;28;3219-3226

Pacientii peste 70 de ani beneficiaza = < 70 de ani

Toxicitatea 5FU = la < sau > 70 de ani
Aditia LOHP la pac peste 70 de ani creste toxicitatea fara
avantaj de OS

3 versus 6 luni ?

Chimioterapia neoadjuvanta
Separat / parte a unui tratament radioterapeutic la cc
de rect

Chimioterapia neoadjuvanta
Separat / parte a unui tratament radioterapeutic la cc de rect
T3 mai ales cu invazia tesutului perirectal, T4, N+,
/ perete anterior

T2 situat jos

7 zile
6-8 sapt

Evaluarea chimioterapiei
neoadjuvante

Cc de rect tratament adjuvant

Cc de colon / rect metastatic

1.Ocluzie/ perforatie

2.Rezectie metastaz

3.Rezectie tu primar

Cei mai multi pacienti cu mCRC se prezinta intial cu metastaze

nerezecabile: cresterea OS este obiectivul principal al
tratamentului
Initial nerezecabili

Categorie

Rezecabil
10%

Strategia
tratamentului

Rezectie

Rezecabil la
limita
2030%

CT +
biologic

Nerezecabili
6070%

CT +
biologic

Recadere
Rezultatul dorit

Rezectie
curativa

Maximizarea OS, si mentinerea QoL

Supravietuirea globala in studiile de faza III

1997

2007

2013

~12 luni1*

>20 luni25

>30 luni6,7

*Bazate pe o meta-analiza
de >19 trials of 5-FU/LV

1. Thirion, et al. JCO 2004; 2. Hurwitz, et al. NEJM 2004

3. Van Cutsem, et al. NEJM 2009; 4. Van Cutsem, et al. JCO 2007
5. Goldberg, et al. Oncologist 2007; 6. Falcone, et al. ASCO 2013; 7. Takahari, et al. ASCO 2013

Cc de rect metastatic

Cc de colon / rect metastatic

Cc de colon / rect metastatic

Cc de colon / rect metastatic

Draft NICE Quality Standard for Colorectal Cancer

(Publication due Aug 2012)
1. People presenting with symptoms suggesting colorectal cancer are referred to the designated colorectal diagnostic
service within 1 day of the decision to refer.
2. People with suspected colorectal cancer without major comorbidity are offered colonoscopy to confirm the diagnosis,
or CT colonography only if colonoscopy is difficult or unsafe.
3. People with colorectal cancer are offered contrast-enhanced CT of the chest, abdomen and pelvis to determine the
stage of the disease, and those with rectal cancer are additionally offered MRI to assess the risk of local recurrence.
4. People with rectal cancer are offered a preoperative treatment strategy appropriate to their risk of local disease
recurrence.
5.People with acute left-sided large bowel obstruction confirmed by CT are offered a colonic stent, if clinically appropriate,
inserted within 24 hours by anendoscopist or radiologist experienced in using colonic stents, in consultation with the
colorectal surgeon.
6. People with locally excised, pathologically confirmed stage I colorectal cancer whose tumour had involved resection
margins (less than 1 mm) are offered further treatment by the colorectal cancer multidisciplinary team.
7. People with stage I rectal cancer are offered advice and options for further treatment from an early rectal cancer
multidisciplinary team.
8.People with resectable colorectal cancer are offered laparoscopic surgery as an alternative to open resection if
suitable, performed by surgeons competent in this technique.
9. People with a CT scan suggesting liver metastatic colorectal cancer are referred to the hepatobiliary
multidisciplinary team to decide whether further imaging is needed to confirm suitability for surgery or
other interventions.
10. People with advanced and metastatic colorectal cancer whose disease progresses after first-line
chemotherapy are offered second-line chemotherapy if they are able to tolerate it.
11. People free from disease after treatment for colorectal cancer are offered regular surveillance.
12. People treated for colorectal cancer and their families or carers are offered specific information on managing the
effects of the treatment on bowel function.

ESMO 2012: Consensus proposals for selection of 1st line

regimen by patient group
KRAS wt

KRAS mt

G1

FOLFIRI/FOLFOX + cet
FOLFOX + pani
FOLFIRI/XELIRI + BEV
FOLFOX/XELOX + BEV
FOLFOXIRI
FOLFOX/XELOX or FOLFIRI/XELIRI
IRIS

+++
+++
++(+)
++(+)
++(+)
+
+

FOLFOX/XELOX + BEV
FOLFOXIRI
FOLFIRI/XELIRI + BEV
FOLFOX/XELOX
FOLFIRI/XELIRI
IRIS

+++
++(+)
++(+)
+
+
+

G2

FOLFIRI + cet
FOLFOX + pani
FOLFOX/XELOX + BEV
FOLFIRI/XELIRI + BEV
FOLFOXIRI
FOLFOX + cet
FOLFOX/XELOX or FOLFIRI/XELIRI
IRIS

+++
+++
+++
++(+)
+(+)
+(+)
+
+

FOLFOX/XELOX + BEV
FOLFIRI/XELIRI + BEV
FOLFOX/XELOX
FOLFIRI/XELIRI
FOLFOXIRI
IRIS

+++
++(+)
++
++
++
+

G3

FUFOL/capecitabine +/- BEV

FOLFIRI/XELIRI or XELOX/FOLFOX
IRIS
Cet/pani (mono)
Watchful waiting
Triplets (+/- BEV/cet/pani)

+++
++
+
(+)
+*
+*

FUFOL/capecitabine +/- BEV

XELOX/FOLFOX
FOLFIRI/XELIRI
IRIS
Watchful waiting
Triplets (+/- BEV)

+++
++
++
+
+*
+*

*Selected patients; +/++/+++/(+) Consensus recommendation reflecting likelihood/uncertainty of efficacy.

They can be modified according to individual patients situation and experience.
Schmoll H-J, et

al. Ann Oncol 2012;23:24792516

Secvena corect de
tratament?
Rolul interveniei chirurgicale la cazuri la

care nu avem tulburri de tranzit sau

sngerare?
Cochrane Database Syst Rev. 2012 Aug 15;8

Non-resection versus resection for an asymptomatic primary tumour in

patients with unresectable stage IV colorectal cancer.
Cirocchi R, Trastulli S, Abraha I, Vettoretto N, Boselli C, et all.
Randomised controlled trials and non-randomised controlled studies
A total of 798 studies
1.086 patients (722 patients treated with primary tumour resection,
and 364 patients managed first with chemotherapy and/or
radiotherapy).
Resection of the primary tumour in asymptomatic patients .... is not
associated with a consistent improvement in overall survival.....
does not significantly reduce the risk of complications from the

Ann Surg Oncol. 2008 Dec;15(12):3440-6.

Chemotherapy has also an effect on primary tumor in colon carcinoma.
Karoui M, et all.
CT induces major histological response in 70% of colon cancers.
Response to CT in the primary and the corresponding liver metastases
are correlated.
These results support a policy of initial CT management for stage IV
colon cancer and may warrant future studies of neoadjuvant CT in
locally advanced colon carcinomas.

Mutation and Copy Number Discordance in Primary vs. Metastatic Colorectal Cancer (mCRC)<br />

Presented By Scott Kopetz at 2014 ASCO Annual Meeting

Study population

Presented By Scott Kopetz at 2014 ASCO Annual Meeting

Low Concordance Between Primary and Metastases for PIK3CA and Minor Genes

Presented By Scott Kopetz at 2014 ASCO Annual Meeting

Synchronous vs Metachronous

Presented By Scott Kopetz at 2014 ASCO Annual Meeting

Intervening Chemotherapy

Presented By Scott Kopetz at 2014 ASCO Annual Meeting

Discordance by Treatment: PIK3CA and Minor Genes

Presented By Scott Kopetz at 2014 ASCO Annual Meeting

Discordance by Tissue Site

Presented By Scott Kopetz at 2014 ASCO Annual Meeting

No Evidence that Discordance is <br />Due to Sampling from Biopsies

Presented By Scott Kopetz at 2014 ASCO Annual Meeting