Principles of adjuvant chemotherapy for colorectal cancer
Adjuvant therapy is not recommended for patients with stage I (T1-2N0M0) or with contraindications to radiotherapy.
For patients with stage II colorectal cancer, the following high-risk factors should be identified: poor histological differentiation (grade III or IV), T4, vascular-lymphatic infiltration, preoperative intestinal obstruction/bowel perforation, and specimen detection.
tubular infiltration, preoperative intestinal obstruction/perforation, and insufficient lymph nodes (less than 12) detected in the specimen.
For stage II colorectal cancer without high-risk factors, follow-up observation or chemotherapy with single-agent fluorouracil-based drugs is recommended.
For stage II colorectal cancer with high-risk factors, adjuvant chemotherapy is recommended. The chemotherapy regimen recommended is 5-FU/LV, capecitabine, 5-FU/LV/oxaliplatin or CapeOx regimen. The duration of chemotherapy should not exceed 6 months. Testing of tissue specimens for MMR or MSI is recommended when available, and single-agent adjuvant chemotherapy with fluorouracil-based agents is not recommended if dMMR or MSI-H is present.
For patients with stage III colorectal cancer, adjuvant chemotherapy is recommended. The chemotherapy regimen recommended is 5-FU/CF, capecitabine, FOLFOX or FLOX (oxaliplatin + fluorouracil + aldehydic folic acid) or CapeOx regimen. Chemotherapy should not be administered for more than 6 months.
Adjuvant chemotherapy regimens for colorectal cancer
FOLFOX4
Oxaliplatin 85 mg/m² 2-hour intravenous infusion, day 1
LV200 mg/m² intravenous infusion over 2 hours, day 1 and 2
5-FU 400 mg/m² IV push, then 600 mg/m² continuous IV infusion over 22 hours, repeated every 2 weeks on day 1 and day 2
mFOLFOX6
Oxaliplatin 85 mg/m²intravenous infusion over 2 hours, day 1
LV400 mg/m²intravenous infusion over 2 hours, day 1 and day 2
5-FU400 mg/m²IV push, day 1, then 1200 mg/m²/d*2 days continuous IV infusion, repeated every 2 weeks
CapeOX
Oxaliplatin 130 mg/m², day 1
Capecitabine (Siroda) 850-1000 mg/m², twice daily for 14 days Repeat every three weeks
FOLFIRI
Irinotecan 180 mg/m²IV infusion over 30-120 minutes, day 1
LV400 mg/m² concurrent infusion with irinotecan but before 5-FU, day 1 and day 2
5-FU 400 mg/m²IV push followed by 600 mg/m²continuous IV infusion over 22 hours, repeated every two weeks on day one and day two
Irinotecan 180 mg/m²IV infusion over 30-120 minutes, day one
LV400 mg/m²concurrent infusion with irinotecan, day 1
5-FU400 mg/m²IV push, day 1, then 1200 mg/m²/d*2 days continuous IV infusion (total 2400 mg/m², infusion 46-48 hours) Repeat every 2 weeks
Bevacizumab + 5-FU-containing regimen
Bevacizumab 5 mg/Kg IV infusion repeated every two weeks + 5-FU + LV or FOLFOX or FOLFIRI
Bevacizumab 7.5mg/Kg IV infusion, repeated every three weeks + CapeOX
The LV used in Europe is dextro LV at a dose of 200 mg/m², while dextro LV is not yet available in the United States. Dextrorubic LV 200 mg/m² is equivalent to LV 400 mg/m².
The NCCN recommends limiting chemotherapy medical orders to 24 hours (i.e., using an expression of 1200 mg/m²/d rather than 2400, infused over 46 hours) to minimize medical errors.
Most of the safety and efficacy data for this regimen are from Europe, and the standard regimen is a starting dose of capecitabine of 1000 mg/m² twice daily for 14 days, repeated every 21 days. There is evidence of greater toxicity in North American patients treated with capecitabine (as is the case with other fluorouracil drugs), and therefore the dose of capecitabine needs to be reduced. The relative effectiveness of the lower starting dose of capecitabine in the CapeOX regimen has not been demonstrated in large follow-up studies.