Abstract
Background
Epidemiologic and preclinical data suggest isoflavones have anticancer activity in colorectal malignancy prevention and treatment. This is the first clinical trial assessing safety and tolerability of Genistein in combination with chemotherapy in metastatic colorectal cancer.
Methods
Patients who had histologically confirmed metastatic colorectal cancer and had not received previous treatment were eligible to enroll. Subjects were treated with FOLFOX or FOLFOX–Bevacizumab as per the investigator choice. Genistein was administered orally for 7 days every 2 weeks, beginning 4 days prior to chemotherapy and continuing through days 1–3 of infusional chemotherapy. Primary endpoint was safety and secondary endpoints included cycle 6 response rate, best overall response rate (BOR), and median progression-free survival (PFS).
Results
Thirteen patients received chemotherapy with Genistein in this trial. The most common adverse events related to Genistein alone were mild and included headaches, nausea, and hot flashes. One subject was observed to have grade 3 hypertension. No increase in chemotherapy-related adverse events was observed when Genistein was added. BOR and median PFS were 61.5% and 11.5 months, respectively.
Conclusion
We observed that adding Genistein to FOLFOX or FOLFOX–Bevacizumab was safe and tolerable. Efficacy results are notable and warrant verification in larger clinical trials.
Clinical trial registration
The study was registered at ClinicalTrials.gov Identifier: NCT01985763.
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Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Acknowledgements
The authors thank DSM Pharmaceuticals for providing Genistein (in kind).
Funding
Institutional funds were received from the Icahn School of Medicine at Mount Sinai.
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Conception and design: SP and RFH. Acquisition of data: SP, RFH, SD, and CA. Analysis and interpretation of data: SP, SD, EM, and NZ. Drafting and critical revision of the manuscript: SP, SD, RFH, CA, EM, and NZ. Final approval of the manuscript: SP, SD, RFH, CA, EM, and NZ.
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S.P. had received fees for advisory board and speaking engagement from Celgene.
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The study was performed in accordance with the Declaration of Helsinki and Good Clinical Practice Guidelines. Approval of the protocol was obtained from the Mount Sinai institutional review board.
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Written informed consent was obtained from all patients before study participation.
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Pintova, S., Dharmupari, S., Moshier, E. et al. Genistein combined with FOLFOX or FOLFOX–Bevacizumab for the treatment of metastatic colorectal cancer: phase I/II pilot study. Cancer Chemother Pharmacol 84, 591–598 (2019). https://doi.org/10.1007/s00280-019-03886-3
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DOI: https://doi.org/10.1007/s00280-019-03886-3