After surgery for stage 3 colon cancer, additional (adjuvant) chemotherapy lowers the risk of the disease coming back, but the drug oxaliplatin can cause lasting numbness and tingling in the hands and feet. This large study of more than 12 thousand patients showed that for many lower-risk patients, especially with the CAPOX regimen (capecitabine tablets + oxaliplatin injections), 3 months of treatment gives nearly the same result as 6 months and cuts nerve damage to about one-third. In higher-risk patients, continuing treatment for 6 months may be slightly more helpful. Your doctor decides the length of treatment based on the exact stage of the tumour and your circumstances.
Stage III colon cancer after surgery; patient suitable for oxaliplatin
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Oxaliplatin | 130 mg/m² | IV | Day 1 |
| Capecitabine | 1000 mg/m² twice daily | Oral | Days 1–14 |
Treatment duration based on IDEA; doses from the FDA label for capecitabine (a maximum of 8 cycles in the adjuvant setting).
On the page “Colorectal cancer” · Stage III colon cancer: adjuvant chemotherapy
Stage III colon cancer after surgery; alternative to CAPOX
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Oxaliplatin | 85 mg/m² | IV over 2 h | Day 1 |
| Leucovorin | 400 mg/m² | IV over 2 h | Day 1 |
| Fluorouracil (bolus) | 400 mg/m² | IV bolus | Day 1 |
| Fluorouracil (infusion) | 2400 mg/m² | IV, continuous 46-h infusion | Starting day 1 |
Doses from the ATOMIC trial (mFOLFOX6 arm). In IDEA, unlike CAPOX, three months of FOLFOX was not as effective as six months, and longer treatment gave better disease-free survival, particularly in high-risk patients. The regimen in the FDA label is FOLFOX4: oxaliplatin 85 and leucovorin 200 mg/m² over 2 hours, then fluorouracil 400 mg/m² as a bolus and 600 mg/m² as a 22-hour infusion on day 1, and leucovorin and fluorouracil at the same doses on day 2; every 14 days for up to 12 cycles.
Oxaliplatin modifications per the label (adjuvant setting): persistent grade 2 sensory neuropathy → consider reducing to 75 mg/m²; persistent grade 3 → consider discontinuing; grade 4 → discontinue. Grade 4 or febrile neutropenia, or grade 3–4 thrombocytopenia → delay until neutrophils ≥1,500 and platelets ≥75,000/µL, then give oxaliplatin 75 mg/m². Creatinine clearance below 30 mL/min → oxaliplatin 65 mg/m².
On the page “Colorectal cancer” · Stage III colon cancer: adjuvant chemotherapy
Colorectal cancer: adjuvant stage 3 and high-risk stage 2, and metastatic disease (with bevacizumab, or an anti-EGFR antibody in RAS wild-type); gastric and oesophageal cancer
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Oxaliplatin | 85 mg/m² | IV over 2 hours | Day 1 |
| Leucovorin (folinic acid) | 400 mg/m² | IV over 2 hours, at the same time as oxaliplatin | Day 1 |
| Fluorouracil | 400 mg/m² | IV bolus | Day 1 |
| Fluorouracil | 2400 mg/m² | Continuous 46-hour infusion | Starting on day 1 |
Doses as in the NSABP C-08 study. Levofolinic acid 200 mg/m² is equivalent to leucovorin 400.
Dose source:.
On the page “FOLFOX (mFOLFOX6): dose, schedule and side effects”
Colorectal cancer (adjuvant and metastatic), gastric cancer
| Drug | Dose | Route | Schedule |
|---|---|---|---|
| Oxaliplatin | 130 mg/m² | IV over 2 hours | Day 1 |
| Capecitabine | 1000 mg/m² twice a day | Oral, within 30 minutes after food | Evening of day 1 to morning of day 15 |
Doses as in the NO16968 study.
On the page “CAPOX (XELOX): dose, schedule and side effects”
Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.
3 months of adjuvant chemotherapy: FOLFOX (FOLFOX4 or mFOLFOX6; 6 two-weekly cycles) or CAPOX (4 three-weekly cycles); the choice of regimen was left to the physician, and the US and Canadian trial (CALGB/SWOG 80702) allowed only mFOLFOX6.
mFOLFOX6 in CALGB/SWOG 80702 every 2 weeks: oxaliplatin 85 mg/m² IV over 2 hours, leucovorin 400 mg/m² IV over 2 hours, fluorouracil 400 mg/m² IV bolus, then 2400 mg/m² continuous infusion over 46 to 48 hours. The FOLFOX4 and CAPOX doses are in the protocol of each trial and are not given in the paper.
6 months of adjuvant chemotherapy with the same regimens: FOLFOX (12 two-weekly cycles) or CAPOX (8 three-weekly cycles). Doses as in the 3-month group.
Source of the regimen details: Full text of the paper (PMC6426127): five trials used FOLFOX4 or mFOLFOX6 or CAPOX and the US/Canadian trial used only mFOLFOX6; mFOLFOX6 doses from ClinicalTrials.gov NCT01150045 (CALGB/SWOG 80702); the doses of each regimen in the other trials are in their protocols and are not given in the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Patients with stage 3 colon cancer after complete resection who were candidates for adjuvant chemotherapy with FOLFOX or CAPOX; enrolment from June 2007 to December 2015. The choice between FOLFOX and CAPOX was not randomised.
Primary endpoint: 3-year disease-free survival rate (non-inferiority of 3 months versus 6 months).
Other: adverse events, especially oxaliplatin-induced neuropathy (neurotoxicity); exploratory analyses by regimen and risk group.
Shorter treatment, regardless of regimen, was associated with significantly fewer adverse events. Grade 2 or higher neurotoxicity during treatment and one month after it was 16.6% (FOLFOX) and 14.2% (CAPOX) in the 3-month group and 47.7% (FOLFOX) and 44.9% (CAPOX) in the 6-month group. Diarrhoea, neutropenia, thrombocytopenia, nausea, mucositis and fatigue were also less frequent with shorter treatment.
The IDEA results were incorporated into the ESMO guideline for localised colon cancer (2020): the duration of oxaliplatin-based adjuvant therapy in stage 3 can be 3 or 6 months for CAPOX [I, A] and 6 months for FOLFOX [I, A], and adaptation by risk subgroup (3 months of CAPOX for T1-3 N1; 6 months for T4 or N2) should be done with caution because the analysis was exploratory. This analysis made shorter treatment the common standard for low-risk patients.
The choice of FOLFOX or CAPOX was not randomised; the trials were run in heterogeneous settings and countries; the risk subgroup analyses were exploratory and not adjusted for multiple comparisons; stopping oxaliplatin at month 3 while continuing the fluoropyrimidine (a common clinical approach) was not tested.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.
Who are you reading this site as?
Your choice applies to every page; change it any time from the bottom of the page.
Type to search...