Is it safe to use Soy Isoflavone Genistein along with Chemotherapy for Metastatic Colorectal Cancer?

Highlights

A clinical study has demonstrated that it is safe to use the soy isoflavone Genistein supplement along with the combination chemotherapy FOLFOX in the treatment of metastatic colorectal cancer patients. Combining Genistein supplements intake with chemotherapy has the potential for improving the FOLFOX chemotherapy treatment outcomes in metastatic colorectal cancer patients.

Metastatic Colorectal Cancer

Metastatic Colorectal Cancer (mCRC) has poor prognosis with a 2-year survival being less than 40% and a 5-year survival being less than 10%, despite the very aggressive combination chemotherapy treatment options. (AJCC Cancer Staging Handbook, 8th Edn).

Metastatic Colorectal Cancer Chemotherapy Regimens

Metastatic Colorectal cancer regimens include 5-Fluorouracil along with a platinum drug Oxaliplatin, with or without the antiangiogenic (inhibits formation of blood vessels to the tumor) agent Bevacizumab (Avastin). New regimens including FOLFIRI (fluorouracil, leucovorin, irinotecan), FOLFOX (5-Fuorouracil, oxaliplatin), CAPOX (capecitabine, oxaliplatin) and FOLFOXIRI (fluorouracil, oxaliplatin, leucovorin, irinotecan) have also shown promising results in mCRC patients.

Here, we will discuss prominent mCRC regimens that are in clinical trials and are considered effective against Metastatic Colorectal Cancer (mCRC).

Efficacy of FOLFOXIRI in Metastatic Colorectal Cancer Patients

Multiple studies have focused on different metastatic colorectal cancer regimens and their efficacy in mCRC patients. FOLFOXIRI is a first-line combination therapy mCRC which includes fluorouracil, oxaliplatin, leucovorin and irinotecan drug combinations. In the TRIBE trial, recently published in 2020, the reintroduction of FOLFOXIRI with bevacizumab resulted in far better outcomes than FOLFIRI  plus bevacizumab but with the chance of higher toxicity as a greater duration of chemotherapy was required and several acute adverse effects were observed in such patients (Glynne-Jones R, et al. The Lancet Oncology, 2020). This strategy of combining effective but cytotoxic drugs with antiangiogenic drugs has raised some concerns for oncologists with regards to safety and toxicity. 

Details of a Meta-analysis: XELOX vs. FOLFOX in Metastatic Colorectal Cancer

A study in 2016 by Guo Y, et al. compared efficacy of capecitabine and fluorouracil, each combined with oxaliplatin, in mCRC patients in combination with chemotherapy (Guo, Yu et al. Cancer investigation, 2016).

• Eight randomized controlled trials (RCTs) were utilized for analysis involving 4,363 patients in total.
• The primary endpoint of the study was to evaluate the safety and efficacy of chemotherapy regimens XELOX (capecitabine plus oxaliplatin) vs. FOLFOX (fluorouracil plus oxaliplatin) in metastatic colorectal cancer patients.
• A total of 2,194 patients were treated with the regimen of XELOX whereas 2,169 patients were treated with FOLFOX regimen.

Results of a Meta-analysis: XELOX vs. FOLFOX in Metastatic Colorectal Cancer

• XELOX group had a higher incidence of hand-foot syndrome, diarrhea and thrombocytopenia whereas FOLFOX group had a higher incidence of neutropenia only.
• The toxicity profiles obtained from the pooled analysis for both groups were different but further research on this matter is required.
• The efficacy of XELOX for mCRC patients is similar to FOLFOX efficacy.

Genistein Supplements for Cancer

Genistein is an isoflavone naturally found in foods such as soy and soybean products. Genistein is also available in the form of dietary supplements and is known to have many health benefits duets to its antioxidant, anti-inflammatory and anti-cancer properties. Some of the other general health benefits of genistein supplements (in addition to anti-cancer properties) include:

• May help reduce blood sugar levels
• May help reduce menopause symptoms
• May help improve heart health
• May promote bone and brain health

In this blog we will discuss whether Genistein supplement use has benefits in metastatic colorectal cancer patients.

Genistein Supplement Use in Colorectal Cancer

Multiple studies have shown an association of lower risk of colorectal cancers in east Asian populations that eat a Soy-rich diet. There are many preclinical experimental studies that have demonstrated the anti-cancer properties of the soy isoflavone Genistein, and its ability to reduce chemotherapy resistance in cancer cells. Hence, researchers at the Icahn School of Medicine at Mount Sinai, in New York, tested the safety and efficacy of using soy isoflavone Genistein along with the standard of care combination chemotherapy in a prospective clinical study in metastatic colorectal cancer patients. (NCT01985763) (Pintova S et al, Cancer Chemotherapy & Pharmacol., 2019)

Details of the Clinical Study on Genistein Supplement use in Colorectal Cancer

• There were 13 patients with mCRC with no prior treatment who were treated with the combination of FOLFOX and Genistein (N=10) and FOLFOX + Bevacizumab + Genistein (N=3).
• Primary endpoint of the study was to assess safety and tolerability of using Genistein with the combination chemotherapy. The secondary endpoint was to assess the best overall response (BOR) after 6 cycles of chemotherapy.
• Genistein at a dose of 60 mg/day, was given orally for 7 days every 2 weeks, beginning 4 days prior to the chemo and continuing through days 1-3 of chemo infusion. This allowed the researchers to assess the side-effects with Genistein alone and in the presence of chemo.

Results of the Clinical Study on Genistein Supplement use in Colorectal Cancer

• The combination of Genistein with chemotherapy was found to be safe and tolerable.
• Adverse events reported with Genistein alone were very mild, such as headache, nausea and hot flashes.
• Adverse events reported when Genistein was given along with the chemotherapy were related to the chemotherapy side-effects, such as neuropathy, fatigue, diarrhea, however, none of the patients experienced a very severe grade 4 adverse event.
• There was an improvement in best overall response (BOR) in these mCRC patients taking the chemotherapy along with Genistein, when compared to those reported for the chemotherapy treatment alone in earlier studies. BOR was 61.5% in this study vs. 38-49% in previous studies with the same chemotherapy treatments. (Saltz LB et al, J Clin Oncol, 2008)
• Even the progression free survival metric, that indicates the amount of time that the tumor has not progressed with the treatment, was a median of 11.5 months with Genistein combination vs. 8 months for chemotherapy alone based on a prior study. (Saltz LB et al, J Clin Oncol., 2008)

Conclusion

This study, although on a very small number of patients, demonstrates that using soy isoflavone Genistein supplement along with the combination chemotherapy was safe and did not increase the toxicity of the chemotherapy in Colorectal Cancer. In addition, using Genistein in combination with FOLFOX has the potential to improve the treatment efficacy and possibly reduce the side-effects of the chemotherapy. These findings, although promising, will need to be evaluated and confirmed in larger clinical studies.

What food you eat, and which supplements you take is a decision you make. Your decision should include consideration of the cancer gene mutations, which cancer, ongoing treatments and supplements, any allergies, lifestyle information, weight, height and habits.

The nutrition planning for cancer from addon is not based on internet searches. It automates the decision making for you based on molecular science implemented by our scientists and software engineers. Irrespective of whether you care to understand the underlying biochemical molecular pathways or not – for nutrition planning for cancer that understanding is needed.

Get started NOW with your nutrition planning by answering questions on the name of cancer, genetic mutations, ongoing treatments and supplements, any allergies, habits, lifestyle, age group and gender.

What food you eat and which supplements you take is a decision you make. Your decision should include consideration of the cancer gene mutations, which cancer, ongoing treatments and supplements, any allergies, lifestyle information, weight, height and habits.

The nutrition planning for cancer from addon is not based on internet searches. It automates the decision making for you based on molecular science implemented by our scientists and software engineers. Irrespective of whether you care to understand the underlying biochemical molecular pathways or not - for nutrition planning for cancer that understanding is needed.

Get started NOW with your nutrition planning by answering questions on the name of cancer, genetic mutations, ongoing treatments and supplements, any allergies, habits, lifestyle, age group and gender.

Cancer patients often have to deal with different chemotherapy side effects which affect their quality of life and look out for alternative therapies for cancer. Taking the right nutrition and supplements based on scientific considerations (avoiding guesswork and random selection) is the best natural remedy for cancer and treatment related side-effects.

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