From the Guidelines
Total neoadjuvant therapy (TNT) for colon cancer is a proposed approach to improve adherence, decrease distant metastases, and ultimately improve overall survival, particularly in locally advanced cases. This approach includes neoadjuvant chemotherapy and either short-course radiation or long-course chemoradiation therapy (CRT) 1. The use of TNT in colon cancer is not as established as in rectal cancer, where it has become a standard practice due to its benefits in local control and reduced toxicity 1.
For colon cancer, neoadjuvant therapy may be considered in specific situations such as locally advanced disease (T4 tumors invading adjacent structures) or cases with high-risk features, as outlined in guidelines for the management of colon cancer 1. Common regimens for neoadjuvant therapy in colon cancer include FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) or CAPOX (capecitabine plus oxaliplatin) for 3-4 months before surgery. For patients with BRAF mutations, targeted therapies might be added to the regimen.
The goal of neoadjuvant therapy in colon cancer is to downstage the tumor, increase the likelihood of complete surgical resection, and potentially improve long-term outcomes. Treatment decisions should be individualized through multidisciplinary tumor board discussions, considering the specific characteristics of the patient and the tumor. Patients receiving neoadjuvant therapy require careful monitoring for toxicities, including neuropathy, diarrhea, and myelosuppression, with appropriate dose adjustments as needed.
Key considerations for the use of TNT in colon cancer include:
- The potential for improved overall survival and decreased distant metastases
- The importance of individualized treatment planning based on tumor characteristics and patient factors
- The need for careful monitoring and management of treatment-related toxicities
- The role of multidisciplinary tumor board discussions in guiding treatment decisions
Given the most recent and highest quality evidence, the use of TNT in colon cancer should be considered on a case-by-case basis, particularly for locally advanced disease or high-risk features, with careful consideration of the potential benefits and risks 1.
From the FDA Drug Label
Adjuvant treatment in patients with Dukes' C colon cancer is recommended for a total of 6 months, ie, XELODA 1250 mg/m2 orally twice daily for 2 weeks followed by a 1-week rest period, given as 3-week cycles for a total of 8 cycles (24 weeks)
The total neoadjuvant therapy for colon cancer using capecitabine is 6 months, with a dose of 1250 mg/m2 orally twice daily for 2 weeks, followed by a 1-week rest period, given as 3-week cycles for a total of 8 cycles (24 weeks) 2.
- Key points:
- Total duration: 6 months
- Dose: 1250 mg/m2 orally twice daily
- Cycle: 2 weeks of treatment + 1 week of rest
- Total cycles: 8 cycles
From the Research
Total Neoadjuvant Therapy for Colon Cancer
- Total Neoadjuvant Therapy (TNT) is a novel approach for locally advanced rectal cancer, which attempts to deliver both systemic chemotherapy and neoadjuvant chemoradiotherapy prior to surgery 3.
- The efficacy and safety of TNT remain controversial in randomized controlled trials (RCTs), but a meta-analysis demonstrated a statistically significant improvement in the pathologic complete response (pCR) rate for TNT treatment 3.
- TNT treatment also showed improvements in disease-free survival (DFS) and overall survival (OS) outcomes compared with standard chemoradiotherapy 3.
Benefits of Total Neoadjuvant Therapy
- TNT has been shown to improve the disease-free and metastasis-free survival, pathologic complete response, and overall survival when compared to standard chemoradiotherapy 4.
- TNT may also increase organ preservation and has the potential to be used in personalized medicine 4.
- The use of TNT has been increasing in recent years, but the long-term overall survival characteristics of this approach are currently unknown 5.
Comparative Effectiveness of Total Neoadjuvant Therapy
- A retrospective study compared the overall survival (OS) and rates of pathologic complete response (pCR) between TNT and standard adjuvant chemotherapy, and found no significant differences in OS, but higher pCR rates among TNT patients 5.
- A cost-effectiveness analysis of TNT with selective nonoperative management for locally advanced rectal cancer found that TNT was cost-effective and dominated standard of care in all sensitivity analyses except when standard of care omitted adjuvant chemotherapy without an impact on disease-free survival 6.
Ongoing Research and Future Directions
- Future directions include integration of immunotherapy, use of TNT in early-stage disease, and determining optimal components of TNT, such as type of chemotherapy and type of radiotherapy 4.
- Additional analyses are needed to validate the cost-effectiveness of TNT with selective nonoperative management from a societal perspective and in the context of other emerging treatment paradigms for locally advanced rectal cancer 6.