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NCCN Guidelines for Patients



Rectal Cancer, Version 1.2017

Part 6 presents the chemotherapy

pathways used to treat advanced rectal

cancer. There are many options. If one

option doesn’t work or stops working,

another option is given.


Guide 15

maps a treatment path that starts with

oxaliplatin. After oxaliplatin, there are other options

for second-line treatment and beyond. Some of these

options depend on what treatment you’ve had before.

First-line options

FOLFOX and CAPEOX are the two options for first-

line treatment. Bevacizumab may be added to either

regimen. Cetuximab or panitumumab can be added

to FOLFOX to treat tumors with normal



However, neither is likely to work if a


mutation is present.

Oxaliplatin can harm your nervous system. Stopping

oxaliplatin—but not the other drugs—after 3 months

of use may prevent harm. Keep taking the other

drugs for 6 months. If the cancer progresses,

oxaliplatin may be restarted if it was stopped due to

side effects. You should only restart if the side effects

have ended.

Capecitabine in the CapeOx regimen can cause a

side effect known as hand-foot syndrome. Symptoms

include redness, swelling, and pain on the palms

of the hands, bottoms of feet, or both. Sometimes

blisters appear. Your dose of capecitabine may be

changed at the earliest signs of hand-foot syndrome.

Second-line options

Oxaliplatin may not prevent the cancer from

progressing. If this happens, you may start FOLFIRI

or irinotecan. Bevacizumab, ziv-aflibercept, or

ramucirumab may be added. Bevacizumab is

preferred due to less harsh side effects and lower


Cetuximab or panitumumab may be options for

tumors with normal


genes. You must not have

received either drug before. Either drug may be

added to FOLFIRI or irinotecan. If you can’t take

irinotecan, either drug can be used alone.




Guide 15. Oxaliplatin pathway

What are first-line options?


◦◦ Bevacizumab

◦◦ Cetuximab or panitumumab for tumors with




• CAPEOX ± bevacizumab

What are second-line options?

• FOLFIRI or irinotecan ±

◦◦ Bevacizumab or ziv-aflibercept or ramucirumab

◦◦ Cetuximab or panitumumab 1) for tumors with



genes and 2) if neither

drug was received before

• Cetuximab or panitumumab 1) for tumors with



genes and 2) if neither drug

was received before

• Pembrolizumab or nivolumab if dMMR or MSI-H

What are third-line and beyond options?

• Some second-line regimens if not received before

• Regorafenib

• Trifluridine + tipiracil

• Clinical trial

• Best supportive care