Subject: Colon cancer treatment
My sister, who lives in China, has colon cancer and has been treated with FolFox after surgery. She was also tested MSI High.
I have heard that patients of MSI high might not respond well to folfox treatment. Shall she consider stopping the chemotherapy or consider a different chemotherapy medicine? What would be an alternative chemotherapy medicine? Thanks. Ning
I am sorry to learn of your sister’s colon cancer diagnosis. According to the JCO article linked and excerpted below, you are correct in thinking that MSI High colon cancers to not respond to 5-FU chemotherapy. As the second study concludes, “However, these results suggest that patients with MSI colon cancer are more sensitive to a higher dose of FOLFOX.””
The first study does point out however that MSI High colon cancer stage II and III have a modestly better prognosis.
Folfox chemotherapy is very toxic and can cause collateral damage aka side effects.
I can research and provide colon cancer chemotherapy treatments as well as evidence-based integrative therapies (anti-oxidant) that studies have shown enhance the efficacy while reducing toxicity of these chemotherapies. Further I can provide information and research regarding anti-angiogenic nutrition to further reduce the risk of colon cancer relapse.
Let me know if you have any questions.
- Cancer Survivor
- Cancer Coach
- Director PeopleBeatingCancer
“Patients with MSI-H tumors had a modestly better prognosis than those with microsatellite-stable (MSS) or MSI-low (MSI-L) cancers, yet also did not seem to benefit from adjuvant fluorouracil (FU) -based chemotherapy. This resistance to FU is presumably due to incorporation of FU metabolites into DNA rather than inhibition of its effective target, thymidylate synthase.10,11“
“Abstract: 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.
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.
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.”
“Curcumin (diferuloylmethane), which has no discernible toxicity, inhibits initiation, promotion and progression of carcinogenesis. 5-Fluorouracil (5-FU) or 5-FU plus oxaliplatin (FOLFOX) remains the backbone of colorectal cancer chemotherapeutics, but produces an incomplete response resulting in survival of cells (chemo-surviving cells) that may lead to cancer recurrence.
The present investigation was, therefore, undertaken to examine whether addition of curcumin to FOLFOX is a superior therapeutic strategy for chemo-surviving cells.
Forty-eight-hour treatment of colon cancer HCT-116 and HT-29 cells with FOLFOX resulted in 60–70% survival, accompanied by a marked activation of insulin like growth factor-1 receptor (IGF-1R) and minor to moderate increase in epidermal growth factor receptor (EGFR), v-erb-b2 erythroblastic leukemia viral oncogene homolog 2 (HER-2) as well as v-akt murine thymoma viral oncogene homolog 1 (AKT), cyclooxygenase-2 (COX-2) and cyclin-D1.
However, inclusion of curcumin to continued FOLFOX treatment for another 48 h greatly reduced the survival of these cells, accompanied by a concomitant reduction in activation of EGFR, HER-2, IGF-1R and AKT, as well as expression of COX-2 and cyclin-D1.
More importantly, EGFR tyrosine kinase inhibitor gefitinib or attenuation of IGF-1R expression by the corresponding si-RNA caused a 30–60% growth inhibition of chemo-surviving HCT-116 cells.
However, curcumin alone was found to be more effective than both gefitinib and IGF-1R si-RNA mediated growth inhibition of chemo-surviving HCT-116 cells and addition of FOLFOX to curcumin did not increase the growth inhibitory effect of curcumin.
Our data suggest that inclusion of curcumin in conventional chemotherapeutic regimens could be an effective strategy to prevent the emergence of chemoresistant colon cancer cells…”