Glasgow Colorectal Centre  

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Bowel or colorectal cancer is fourth most common cancer in the world and is the fifth most common cause of cancer -related deaths. Post-operative adjuvant chemotherapy for high risk stage II and stage III colorectal cancer improves survival. Most chemotherapy regimes are based on flouropyrimidines chemotherapy. Oxaliplatin has additional benefit when combined with flouropyrimidine-based chemotherapy.  Chemotherapy for colorectal cancer


A recent large scale randomised, multi-centre study reported similar outcomes in terms of disease-free survival (DFS) and overall survival (OS)  for a 3-month regimen of post-operative adjuvant chemotherapy versus a 6-month regimen in patients with high-risk stage II and stage III colorectal cancer. The short duration and however was associated with a significant reduction in toxicity (a reduction in both the severity and duration side effects including peripheral neuropathy) .


The SCOT international study randomised 6065 patients with high-risk stage II and III colorectal cancer into groups receiving either 3 or 6 months of post-operative adjuvant oxaliplatin -containing chemotherapy. The chemotherapy regimens consisted of either CAPOX (capecitabine, trade name Xeloda combined with oxaliplatin) or FOLFOX (folinic acid, fluorouracil and oxaliplatin).


The 3-year DFS  was 76.7% with 3-month chemotherapy group versus 77.1% in the 6-month treatment (NS). Three-year OS was 19.0% in the 3-month group versus 89.6% in the 6-month group (NS).


Significant adverse events (grade 3 - 5) were more common in the 6-month chemotherapy group (59% vs. 36%: P <0.0001).  In particular, troublesome peripheral neuropathy was more common in the 6-month group and was longer lasting and a greater negative impact on quality of life. There were 32 treatment-related deaths (16 in each group) in this group of 6065 patients.


Although the study was underpowered, it suggests that 3 months of oxaliplatin based post-operative adjuvant chemotherapy was not inferior to a 6-month regimen for patients with high-risk colorectal cancer. The 6-month regimen however was associated with a higher risk of side effects. Specifically symptomatic peripheral neuropathy was more frequent and of greater duration leading to a significant reduction in quality life in patients who underwent the 6-month regimen.


This SCOT trial adds to the results of six other studies which have addressed the issue of whether a shorter post-operative course of chemotherapy is as effective as the traditional six month course. A meta-analysis has also been performed by the IDEA collaboration. Overall these data suggest that a 3-month post-operative adjuvant chemotherapy regimen for patients with high-risk colon cancer is as effective as a 6-month regimen and is also associated with fewer side effects which are of shorter duration leading to a better quality of life.


REFERENCES

3 versus 6 months of adjuvant oxaliplatin-fluoropyrimidine combination therapy for colorectal cancer (SCOT): an international, randomised, phase 3, non-inferiority trial.

Iveson TJ, Kerr RS, Saunders MP, Cassidy J et al.

Lancet Oncol. 2018 Apr;19(4):562-578.


The IDEA (International Duration Evaluation of Adjuvant Chemotherapy) Collaboration: prospective combined analysis of phase III Trials investigating duration of adjuvant therapy with the FOLFOX (FOLFOX4 or Modified FOLFOX6) or XELOX (3 versus 6 months) regimen for patients with stage III colon cancer: trial design and current status.

Andre, T, Iveson, T, Labianca, R et al.

Curr Colorectal Cancer Rep. 2013; 9: 261–269

 3-month chemotherapy as effective as 6 months regimen in stage II/III colorectal cancer (April 2018)