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NCCN Guidelines for Patients



Rectal Cancer, Version 1.2017


Guide 17

maps a treatment path that starts with

FOLFOXIRI. After FOLFOXIRI, 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

The FOLFOXIRI pathway starts with both oxaliplatin

and irinotecan. It is an intense regimen and is not for

everybody. It is not advised for stage II or III cancers.

Bevacizumab may be added.

Second-line options

FOLFOXIRI may not prevent the cancer from

progressing. In this happens, there are 5 second-line

options. Some options do not apply to everyone.

Cetuximab or panitumumab may be options for

tumors with normal


genes. However, neither are

likely to work if a


mutation is present.

Either drug may be received with irinotecan. If you’re

unable to take irinotecan, either drug may be used


The cancer cells may have a dMMR system or

MSI-H. The MMR system is explained in Part 2. In

this case, nivolumab or pembrolizumab may be an

option. If these drugs don’t work, your next options

include other second-line options.

There are two other options if the cancer has

progressed on all other regimens. One option is to

receive regorafenib. The other option is trifluridine

with tipiracil.

Third-line and beyond

If the cancer progresses again, one of the second-

line treatments may be an option. If not, there may

be a clinical trial that you could join. Supportive care

may give you relief from symptoms.




Guide 17. FOLFOXIRI pathway

What are first-line options?

• FOLFOXIRI ± bevacizumab

What are second-line options?

• Irinotecan + cetuximab or panitumumab for

tumors with normal



• Cetuximab or panitumumab for tumors with




• Pembrolizumab or nivolumab if dMMR or MSI-H

• Regorafenib

• Trifluridine + tipiracil

What are third-line and beyond options?

• Some second-line regimens if not received before

• Clinical trial

• Best supportive care