Sofya Pintova1,2, Sirish Dharmupari3, Erin Moshier4, Nicole Zubizarreta4, Celina Ang3, Randall F Holcombe3,5. 1. Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine At Mount Sinai, New York, NY, USA. sofya.pintova@mountsinai.org. 2. Mount Sinai Hospital, One Gustave L Levy Place, Box 1128, New York, NY, 10029, USA. sofya.pintova@mountsinai.org. 3. Division of Hematology and Medical Oncology, Department of Medicine, Icahn School of Medicine At Mount Sinai, New York, NY, USA. 4. Department of Population Health Science and Policy, Institute for Healthcare Delivery Science, Icahn School of Medicine At Mount Sinai, New York, NY, USA. 5. University of Hawai'I Cancer Center, Honolulu, HI, USA.
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.
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.