colon cancer. While both CAPOX and | |||||
FOLFOX are considered acceptable | |||||
options, the choice between agents | |||||
depends upon convenience, toxicity | |||||
profile, and patient and physician | |||||
preference. | |||||
The 2020 International Duration | |||||
Evaluation of Adjuvant Chemotherapy | |||||
collaboration( effect of duration | |||||
of adjuvant chemotherapy for | |||||
patients with stage III colon cancer | |||||
) was a pooled analysis of six randomised | |||||
phase III trials, exploring | |||||
three versus six months of adjuvant | |||||
chemotherapy with either CAPOX or FOLFOX. 11 Whereas three months was equivalent to six months for | |||||
CAPOX, the three months of FOLFOX | |||||
yielded an inferior result. As a result, | |||||
and because of its reduced toxicity, | |||||
three months of CAPOX is the current | |||||
standard adjuvant regimen for | |||||
resected stage III colon cancer. | |||||
Adjuvant chemotherapy is not |
standard for resected stage II colon cancers, where a survival benefit has not definitely been shown. It may be considered in cases where there are adverse clinicopathological features, |
Figure 6. Robotic photo of a sigmoid cancer marked with dye. |
||||
including a primary tumour invading |
|||||
into surrounding structures, inadequate lymph node sampling, or |
Figure 7. Ileostomy. |
Table 2. Active agents in colorectal cancer |
|||
|
a presentation with obstruction or perforation, among others. In these situations, only single-agent fluoropyrimidine chemotherapy is used( most commonly capecitabine).
EXTRAPERITONEAL RECTAL CANCERS Patients with full thickness pene-
|
Class
Chemotherapeutic agents
|
Names
Fluorouracil Capecitabine Uracil plus tegafur Oxaliplatin Irinotecan Trifluridine plus tipiracil S-1( in Japan only)
|
|||
tration of the wall( T3 or T4 disease) or likely lymph node metastases( N1 disease) at the time of presentation will generally be offered neoadjuvant treatment before surgery. Postoperatively, the use of adjuvant chemotherapy is tailored to the individual needs of the patient. |
Anti-angiogenics
Targeted therapy
|
Bevacizumab Ramucirumab Aflibercept Regorafenib
Epidermal growth factor receptor inhibitors
• Cetuximab
• Panitumumab
|
|||
Variations in practice occur because a benefit from adjuvant chemotherapy in terms of overall survival has not been clearly or consistently shown across several clinical trials. Chemotherapy is often |
BRAF inhibitors
• Encorafenib
HER2 inhibitors
• Trastuzumab
• Tucatinib
|
||||
withheld if a patient has had a complete pathological response or has lymph node negative disease on the definitive pathological specimen. However, many patients with lymph node positive disease at the time of resection will be offered further |
KRAS-G12C inhibitors
• Sotorasib
• Adagrasib
NTRK inhibitors
• Larotrectinib
• Entrectinib
|
||||
|
chemotherapy postoperatively.
In rectal cancer, radiation therapy is combined with chemotherapy as initial( neoadjuvant) therapy
|
Immunotherapy |
Pembrolizumab Nivolumab Dostarlimab |
|||
before surgery in clinically staged T3 |
|||||
or T4 or node-positive disease. The |
overall survival and local relapse |
unresectable disease. Combinations |
therapies are emerging as treat- |
The condition is found in about |
|
German Rectal Cancer Study Group |
rate compared with long-course |
of these agents have led to median |
ment for metastatic colorectal can- |
15 % of patients across all stages of |
|
randomly assigned 823 patients |
18, 19 chemoradiotherapy. |
progression-free survival of up to |
cer( see table 2). Most of these are |
colorectal cancer, but only in about |
|
with ultrasound-staged T3 or T4 or node-positive rectal cancer to either preoperative chemoradiation therapy or postoperative chemoradiation |
Metastatic or recurrent disease
Treatment of metastatic or recur-
|
12 months, and overall survival of up to 30 months. The addition of targeted therapies— agents that interact with specific molecules or |
yet to achieve regulatory approval in Australia; however, there are trial data supporting their activity when the relevant target is mutated |
5 % of those with metastatic disease, in part due to the relatively favourable prognosis of this subgroup.
Immunotherapy has demon-
|
|
therapy( 50.4 Gy in 28 daily frac- |
rent disease is complex and |
pathways involved in cancer growth |
or over-expressed. The difficulty |
strated superior activity and |
|
tions to the tumour and pelvic lymph |
requires a multidisciplinary |
— have improved results even fur- |
is in identifying these patients, |
improved tolerance compared with |
|
nodes concurrent with infusional 5-FU). 17 The five and 10-year overall survival rates were similar in both |
approach. Before the development of systemic therapies, survival was about four months. The current |
ther. The most established of these are the anti-angiogenic agent bevacizumab, and the epidermal growth |
as many of the requisite molecular changes needed for efficacy only occur relatively infrequently, |
standard chemotherapy in patients with metastatic disease where dMMR / MSI-H status is confirmed, |
|
arms, but local recurrence rates and |
plethora of active treatments has |
factor receptor inhibitors cetuxi- |
and testing for some targets is not |
and the checkpoint inhibitor pem- |
|
|
toxicity was significantly better in the preoperative treatment arm.
The use of short-course radiation therapy before surgery has
|
extended average survival to 24 months. Surgical resection of oligometastatic disease is now a routine procedure and downstaging of |
mab and panitumumab, which are generally well tolerated but do have distinct side effect profiles. For example, bevacizumab is associated |
routine.
Immunotherapy has been disappointing in most patients with colorectal cancer, other than in the
|
brolizumab is PBS-approved for these patients. 20 Research for the use of this approach in the early stages of colorectal cancer with dMMR / |
|
been a standard approach in parts |
tumours with chemotherapy before |
with hypertension, bleeding and |
subset of patients where there is |
MSI-H status is ongoing. |
|
of Europe; it is less commonly used |
resection is standard. |
thrombotic complications, whereas |
a documented defect in the abil- |
Note that although chemotherapy |
|
in Australia. The use of short-course |
There are a number of active |
the epidermal growth factor recep- |
ity to correct mistakes that occur |
and other systemic therapies provide |
|
radiation therapy has been evalu- |
agents, including 5-FU, capecit- |
tor inhibitors are associated with an |
when DNA is copied in cells. This is |
meaningful improvements in sur- |
|
ated in several clinical trials. In all |
abine, oxaliplatin and irinotecan, |
acneiform rash, hypomagnesaemia |
described as either a deficient mis- |
vival, systemic therapy alone will not |
|
trials, short-course radiation ther- |
that extend disease-free survival |
and infusion reactions. |
match repair( dMMR) or a microsat- |
cure metastatic colorectal cancer. |
|
apy was found to be equivalent in |
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