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Microsatellite instability and sensitivitiy to FOLFOX treatment in metastatic colorectal cancer
G des Guetz1, P Mariani, J Cucherousset
1Department of Oncology, Avicenne Hospital, 93009 Bobigny, France. Gaetan.des-guetz@wanadoo.fr
Background:
Microsatelite instability (MSI) is the consequence of the inactivation of a mismatch repair gene and is observed in approximately 15% of colon cancer cases. Patients with MSI colon cancer do not benefit from 5-fluorouracil (5-FU)-based chemotherapy. A current treatment of reference for colon cancer is a combination of 5-FU and oxaliplatin (FOLFOX). The aim of this study was to determine the efficiency of the FOLFOX treatment in patients with metastatic MSI colon cancer.
Patients And Methods:
Tumour specimens were collected from patients with metastatic colon cancer treated with FOLFOX 4 modified or FOLFOX 6; these two regimens are based on 85 mg/m2 and 100 mg/m2 oxaliplatin, respectively. The MSI status was assessed by measuring the length of five monomorphic mononucleotide markers. The FOLFOX regimen was evaluated as a first-line treatment according to WHO criteria.
Results:
Forty patients (22 men, 18 women), median age 63.5 years (27-83 years) were treated with FOLFOX 4 or 6. Nine patients had tumours exhibiting high MSI (MSI group) and 31 patients had tumours exhibiting microsatellite stability (MSS group). In the MSS group, 11 partial responses (36%) were observed, while there were only two in the MSI group (22%) (no significant difference). The two patients who were responders in the MSI group were treated with FOLFOX 6. The overall survival was not significantly different for MSI and MSS patients.
Conclusion:
No significant differences in the overall response rate or overall survival between the two groups of patients were observed. However, these results suggest that patients with MSI colon cancer are more sensitive to a higher dose of FOLFOX.
Insights
Patients with microsatellite instability (MSI) colon cancer did not show significant differences in response to FOLFOX chemotherapy compared to those with microsatellite stability (MSS). However, higher doses of FOLFOX may be more effective for MSI patients.
Area of Science:
- Oncology
- Gastroenterology
- Genetics
Background:
- Microsatellite instability (MSI) occurs in ~15% of colon cancers due to mismatch repair gene inactivation.
- MSI colon cancer patients do not benefit from 5-fluorouracil (5-FU) chemotherapy.
- FOLFOX (5-FU and oxaliplatin) is a standard colon cancer treatment.
Purpose of the Study:
- To evaluate the efficacy of FOLFOX in metastatic MSI colon cancer patients.
- To compare treatment outcomes between MSI and microsatellite stable (MSS) colon cancer patients.
Main Methods:
- Tumor specimens from metastatic colon cancer patients treated with FOLFOX 4 or FOLFOX 6 were analyzed.
- MSI status was determined by analyzing five monomorphic mononucleotide markers.
- Treatment response was assessed using WHO criteria as a first-line therapy.
Main Results:
- Forty patients (9 MSI, 31 MSS) received FOLFOX.
- Partial response rates were 22% for MSI and 36% for MSS (not significant).
- Overall survival did not differ significantly between MSI and MSS groups.
Conclusions:
- No significant difference in overall response or survival between MSI and MSS colon cancer patients treated with FOLFOX.
- Findings suggest potential increased sensitivity of MSI colon cancer to higher FOLFOX doses.
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