Genistein combined with FOLFOX or FOLFOX–Bevacizumab for the treatment of metastatic colorectal cancer: phase I/II pilot study
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 Pati...
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| Vydáno v: | Cancer chemotherapy and pharmacology Ročník 84; číslo 3; s. 591 - 598 |
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| Hlavní autoři: | , , , , , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
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Berlin/Heidelberg
Springer Berlin Heidelberg
01.09.2019
Springer Nature B.V |
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| ISSN: | 0344-5704, 1432-0843, 1432-0843 |
| On-line přístup: | Získat plný text |
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| 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. |
|---|---|
| AbstractList | BackgroundEpidemiologic 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.MethodsPatients 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).ResultsThirteen 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.ConclusionWe 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 registrationThe 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. 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. 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). 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. 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. The study was registered at ClinicalTrials.gov Identifier: NCT01985763. 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.BACKGROUNDEpidemiologic 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.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).METHODSPatients 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).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.RESULTSThirteen 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.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.CONCLUSIONWe observed that adding Genistein to FOLFOX or FOLFOX-Bevacizumab was safe and tolerable. Efficacy results are notable and warrant verification in larger clinical trials.The study was registered at ClinicalTrials.gov Identifier: NCT01985763.CLINICAL TRIAL REGISTRATIONThe study was registered at ClinicalTrials.gov Identifier: NCT01985763. |
| Author | Pintova, Sofya Zubizarreta, Nicole Ang, Celina Moshier, Erin Holcombe, Randall F. Dharmupari, Sirish |
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| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/31203390$$D View this record in MEDLINE/PubMed |
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| Copyright | Springer-Verlag GmbH Germany, part of Springer Nature 2019 Cancer Chemotherapy and Pharmacology is a copyright of Springer, (2019). All Rights Reserved. |
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| References | PantSA first-in-human dose-escalation study of ME-143, a second generation NADH oxidase inhibitor, in patients with advanced solid tumorsInvestig New Drugs2014321879310.1007/s10637-013-9949-41:CAS:528:DC%2BC2cXitFylu74%3D WitteJSRelation of vegetable, fruit, and grain consumption to colorectal adenomatous polypsAm J Epidemiol1996144111015102510.1093/oxfordjournals.aje.a0088721:STN:280:DyaK2s%2Fpslyqsg%3D%3D8942431 HwangJTHaJParkOJCombination of 5-fluorouracil and genistein induces apoptosis synergistically in chemo-resistant cancer cells through the modulation of AMPK and COX-2 signaling pathwaysBiochem Biophys Res Commun2005332243344010.1016/j.bbrc.2005.04.1431:CAS:528:DC%2BD2MXks1Cqt7s%3D15896711 AJCC Cancer Staging Handbook: From the AJCC Cancer Staging Manual 7th edition KonoSRelationship of diet to small and large adenomas of the sigmoid colonJpn J Cancer Res1993841131910.1111/j.1349-7006.1993.tb02777.x1:STN:280:DyaK3s7psVKrsA%3D%3D84498215919037 SolomonLASensitization of ovarian cancer cells to cisplatin by genistein: the role of NF-kappaBJ Ovarian Res2008111110.1186/1757-2215-1-91:CAS:528:DC%2BD1MXht1Sruro%3D UllmannURepeated oral once daily intake of increasing doses of the novel synthetic genistein product Bonistein in healthy volunteersPlanta Med2005711089189610.1055/s-2005-8641861:CAS:528:DC%2BD2MXht1KgtLbE16254818 YanhongHGenistein sensitizes ovarian carcinoma cells to chemotherapy by switching the cell cycle progression in vitroJ Med Coll PLA20092412513510.1016/S1000-1948(09)60028-9 PereiraMAUse of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agentsCarcinogenesis19941551049105410.1093/carcin/15.5.10491:CAS:528:DyaK2cXkvF2htrw%3D8200067 JatoiAIs voluntary vitamin and mineral supplementation associated with better outcome in non-small cell lung cancer patients? Results from the Mayo Clinic lung cancer cohortLung Cancer2005491778410.1016/j.lungcan.2005.01.00415949593 SetchellKDComparing the pharmacokinetics of daidzein and genistein with the use of 13C-labeled tracers in premenopausal womenAm J Clin Nutr200377241141910.1093/ajcn/77.2.4111:CAS:528:DC%2BD3sXptVegtg%3D%3D12540402 FerrucciLMFactors related to the use of dietary supplements by cancer survivorsJ Altern Complement Med200915667368010.1089/acm.2008.0387194897062928474 BusbyMGClinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy menAm J Clin Nutr200275112613610.1093/ajcn/75.1.1261:CAS:528:DC%2BD38XhslylsQ%3D%3D11756070 MukundVGenistein: its role in metabolic diseases and cancerCrit Rev Oncol Hematol2017119132210.1016/j.critrevonc.2017.09.00429065980 MetznerJEStudy on the pharmacokinetics of synthetic genistein after multiple oral intake in post-menopausal womenArzneimittelforschung200959105135201:CAS:528:DC%2BD1MXhsV2ltLrJ19998579 AJCC Cancer Staging Handbook: From the AJCC Cancer Staging Manual 8th edition MariniHUpdate on genistein and thyroid: an overall message of safetyFront Endocrinol20123949410.3389/fendo.2012.00094 UllmannUSafety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteersAdv Ther2005221657810.1007/BF028501861:CAS:528:DC%2BD2MXkvFOku70%3D15943224 NishiMEating habits and colorectal cancerOncol Rep1997459959981:STN:280:DC%2BC3MrjtVWmsw%3D%3D21590181 HaenszelWLarge-bowel cancer in Hawaiian JapaneseJ Natl Cancer Inst19735161765177910.1093/jnci/51.6.17651:STN:280:DyaE2c%2Fmt1Omtg%3D%3D4797262 SaltzLBBevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III studyJ Clin Oncol200826122013201910.1200/JCO.2007.14.99301:CAS:528:DC%2BD1cXlvFaqs7g%3D SpagnuoloCGenistein and cancer: current status, challenges, and future directionsAdv Nutr20156440841910.3945/an.114.0080521:CAS:528:DC%2BC2MXhslOqsLzM261780254496735 FischerLClinical characteristics and pharmacokinetics of purified soy isoflavones: multiple-dose administration to men with prostate neoplasiaNutr Cancer200448216017010.1207/s15327914nc4802_51:CAS:528:DC%2BD2cXmslGqtrk%3D15231450 DeCosseJJGender and colorectal cancerEur J Cancer Prev19932210511510.1097/00008469-199303000-000031:STN:280:DyaK3s3hsVGqtA%3D%3D8461861 ZhangYChenHGenistein attenuates WNT signaling by up-regulating sFRP2 in a human colon cancer cell lineExp Biol Med2011236671472210.1258/ebm.2011.0103471:CAS:528:DC%2BC3MXosFKjt7s%3D MiyakiMCharacteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumorsCancer Res199454301130201:CAS:528:DyaK2cXktVKgtLo%3D8187091 TakimotoCHPhase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancerCancer Epidemiol Biomarkers Prev20031211 Pt 1121312211:CAS:528:DC%2BD3sXptlyjtb4%3D14652284 PintovaSME-143 is superior to genistein in suppression of WNT signaling in colon cancer cellsAnticancer Res20173741647165310.21873/anticanres.114951:CAS:528:DC%2BC1cXitlGhtbbL28373425 HuJFDiet and cancer of the colon and rectum: a case-control study in ChinaInt J Epidemiol199120236236710.1093/ije/20.2.3621:STN:280:DyaK38%2FhtVCltQ%3D%3D1917235 V Mukund (3886_CR11) 2017; 119 M Miyaki (3886_CR14) 1994; 54 LA Solomon (3886_CR15) 2008; 1 S Pintova (3886_CR10) 2017; 37 L Fischer (3886_CR23) 2004; 48 U Ullmann (3886_CR24) 2005; 71 A Jatoi (3886_CR28) 2005; 49 LM Ferrucci (3886_CR27) 2009; 15 W Haenszel (3886_CR5) 1973; 51 C Spagnuolo (3886_CR12) 2015; 6 MA Pereira (3886_CR4) 1994; 15 H Marini (3886_CR18) 2012; 3 S Kono (3886_CR7) 1993; 84 U Ullmann (3886_CR20) 2005; 22 JF Hu (3886_CR6) 1991; 20 JE Metzner (3886_CR19) 2009; 59 MG Busby (3886_CR25) 2002; 75 CH Takimoto (3886_CR22) 2003; 12 H Yanhong (3886_CR16) 2009; 24 3886_CR2 3886_CR1 JJ DeCosse (3886_CR3) 1993; 2 Y Zhang (3886_CR13) 2011; 236 LB Saltz (3886_CR26) 2008; 26 JS Witte (3886_CR9) 1996; 144 KD Setchell (3886_CR21) 2003; 77 S Pant (3886_CR29) 2014; 32 JT Hwang (3886_CR17) 2005; 332 M Nishi (3886_CR8) 1997; 4 |
| References_xml | – reference: SetchellKDComparing the pharmacokinetics of daidzein and genistein with the use of 13C-labeled tracers in premenopausal womenAm J Clin Nutr200377241141910.1093/ajcn/77.2.4111:CAS:528:DC%2BD3sXptVegtg%3D%3D12540402 – reference: HaenszelWLarge-bowel cancer in Hawaiian JapaneseJ Natl Cancer Inst19735161765177910.1093/jnci/51.6.17651:STN:280:DyaE2c%2Fmt1Omtg%3D%3D4797262 – reference: MariniHUpdate on genistein and thyroid: an overall message of safetyFront Endocrinol20123949410.3389/fendo.2012.00094 – reference: HwangJTHaJParkOJCombination of 5-fluorouracil and genistein induces apoptosis synergistically in chemo-resistant cancer cells through the modulation of AMPK and COX-2 signaling pathwaysBiochem Biophys Res Commun2005332243344010.1016/j.bbrc.2005.04.1431:CAS:528:DC%2BD2MXks1Cqt7s%3D15896711 – reference: FerrucciLMFactors related to the use of dietary supplements by cancer survivorsJ Altern Complement Med200915667368010.1089/acm.2008.0387194897062928474 – reference: DeCosseJJGender and colorectal cancerEur J Cancer Prev19932210511510.1097/00008469-199303000-000031:STN:280:DyaK3s3hsVGqtA%3D%3D8461861 – reference: SolomonLASensitization of ovarian cancer cells to cisplatin by genistein: the role of NF-kappaBJ Ovarian Res2008111110.1186/1757-2215-1-91:CAS:528:DC%2BD1MXht1Sruro%3D – reference: AJCC Cancer Staging Handbook: From the AJCC Cancer Staging Manual 8th edition – reference: FischerLClinical characteristics and pharmacokinetics of purified soy isoflavones: multiple-dose administration to men with prostate neoplasiaNutr Cancer200448216017010.1207/s15327914nc4802_51:CAS:528:DC%2BD2cXmslGqtrk%3D15231450 – reference: AJCC Cancer Staging Handbook: From the AJCC Cancer Staging Manual 7th edition – reference: YanhongHGenistein sensitizes ovarian carcinoma cells to chemotherapy by switching the cell cycle progression in vitroJ Med Coll PLA20092412513510.1016/S1000-1948(09)60028-9 – reference: PereiraMAUse of azoxymethane-induced foci of aberrant crypts in rat colon to identify potential cancer chemopreventive agentsCarcinogenesis19941551049105410.1093/carcin/15.5.10491:CAS:528:DyaK2cXkvF2htrw%3D8200067 – reference: BusbyMGClinical characteristics and pharmacokinetics of purified soy isoflavones: single-dose administration to healthy menAm J Clin Nutr200275112613610.1093/ajcn/75.1.1261:CAS:528:DC%2BD38XhslylsQ%3D%3D11756070 – reference: SpagnuoloCGenistein and cancer: current status, challenges, and future directionsAdv Nutr20156440841910.3945/an.114.0080521:CAS:528:DC%2BC2MXhslOqsLzM261780254496735 – reference: UllmannUSafety, tolerability, and pharmacokinetics of single ascending doses of synthetic genistein (Bonistein) in healthy volunteersAdv Ther2005221657810.1007/BF028501861:CAS:528:DC%2BD2MXkvFOku70%3D15943224 – reference: MukundVGenistein: its role in metabolic diseases and cancerCrit Rev Oncol Hematol2017119132210.1016/j.critrevonc.2017.09.00429065980 – reference: ZhangYChenHGenistein attenuates WNT signaling by up-regulating sFRP2 in a human colon cancer cell lineExp Biol Med2011236671472210.1258/ebm.2011.0103471:CAS:528:DC%2BC3MXosFKjt7s%3D – reference: TakimotoCHPhase I pharmacokinetic and pharmacodynamic analysis of unconjugated soy isoflavones administered to individuals with cancerCancer Epidemiol Biomarkers Prev20031211 Pt 1121312211:CAS:528:DC%2BD3sXptlyjtb4%3D14652284 – reference: UllmannURepeated oral once daily intake of increasing doses of the novel synthetic genistein product Bonistein in healthy volunteersPlanta Med2005711089189610.1055/s-2005-8641861:CAS:528:DC%2BD2MXht1KgtLbE16254818 – reference: MiyakiMCharacteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumorsCancer Res199454301130201:CAS:528:DyaK2cXktVKgtLo%3D8187091 – reference: SaltzLBBevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III studyJ Clin Oncol200826122013201910.1200/JCO.2007.14.99301:CAS:528:DC%2BD1cXlvFaqs7g%3D – reference: NishiMEating habits and colorectal cancerOncol Rep1997459959981:STN:280:DC%2BC3MrjtVWmsw%3D%3D21590181 – reference: WitteJSRelation of vegetable, fruit, and grain consumption to colorectal adenomatous polypsAm J Epidemiol1996144111015102510.1093/oxfordjournals.aje.a0088721:STN:280:DyaK2s%2Fpslyqsg%3D%3D8942431 – reference: KonoSRelationship of diet to small and large adenomas of the sigmoid colonJpn J Cancer Res1993841131910.1111/j.1349-7006.1993.tb02777.x1:STN:280:DyaK3s7psVKrsA%3D%3D84498215919037 – reference: PantSA first-in-human dose-escalation study of ME-143, a second generation NADH oxidase inhibitor, in patients with advanced solid tumorsInvestig New Drugs2014321879310.1007/s10637-013-9949-41:CAS:528:DC%2BC2cXitFylu74%3D – reference: HuJFDiet and cancer of the colon and rectum: a case-control study in ChinaInt J Epidemiol199120236236710.1093/ije/20.2.3621:STN:280:DyaK38%2FhtVCltQ%3D%3D1917235 – reference: JatoiAIs voluntary vitamin and mineral supplementation associated with better outcome in non-small cell lung cancer patients? Results from the Mayo Clinic lung cancer cohortLung Cancer2005491778410.1016/j.lungcan.2005.01.00415949593 – reference: PintovaSME-143 is superior to genistein in suppression of WNT signaling in colon cancer cellsAnticancer Res20173741647165310.21873/anticanres.114951:CAS:528:DC%2BC1cXitlGhtbbL28373425 – reference: MetznerJEStudy on the pharmacokinetics of synthetic genistein after multiple oral intake in post-menopausal womenArzneimittelforschung200959105135201:CAS:528:DC%2BD1MXhsV2ltLrJ19998579 – volume: 71 start-page: 891 issue: 10 year: 2005 ident: 3886_CR24 publication-title: Planta Med doi: 10.1055/s-2005-864186 – ident: 3886_CR2 – volume: 2 start-page: 105 issue: 2 year: 1993 ident: 3886_CR3 publication-title: Eur J Cancer Prev doi: 10.1097/00008469-199303000-00003 – volume: 59 start-page: 513 issue: 10 year: 2009 ident: 3886_CR19 publication-title: Arzneimittelforschung – volume: 77 start-page: 411 issue: 2 year: 2003 ident: 3886_CR21 publication-title: Am J Clin Nutr doi: 10.1093/ajcn/77.2.411 – volume: 51 start-page: 1765 issue: 6 year: 1973 ident: 3886_CR5 publication-title: J Natl Cancer Inst doi: 10.1093/jnci/51.6.1765 – volume: 37 start-page: 1647 issue: 4 year: 2017 ident: 3886_CR10 publication-title: Anticancer Res doi: 10.21873/anticanres.11495 – volume: 144 start-page: 1015 issue: 11 year: 1996 ident: 3886_CR9 publication-title: Am J Epidemiol doi: 10.1093/oxfordjournals.aje.a008872 – volume: 119 start-page: 13 year: 2017 ident: 3886_CR11 publication-title: Crit Rev Oncol Hematol doi: 10.1016/j.critrevonc.2017.09.004 – volume: 332 start-page: 433 issue: 2 year: 2005 ident: 3886_CR17 publication-title: Biochem Biophys Res Commun doi: 10.1016/j.bbrc.2005.04.143 – volume: 236 start-page: 714 issue: 6 year: 2011 ident: 3886_CR13 publication-title: Exp Biol Med doi: 10.1258/ebm.2011.010347 – volume: 22 start-page: 65 issue: 1 year: 2005 ident: 3886_CR20 publication-title: Adv Ther doi: 10.1007/BF02850186 – volume: 15 start-page: 1049 issue: 5 year: 1994 ident: 3886_CR4 publication-title: Carcinogenesis doi: 10.1093/carcin/15.5.1049 – volume: 3 start-page: 94 year: 2012 ident: 3886_CR18 publication-title: Front Endocrinol doi: 10.3389/fendo.2012.00094 – volume: 20 start-page: 362 issue: 2 year: 1991 ident: 3886_CR6 publication-title: Int J Epidemiol doi: 10.1093/ije/20.2.362 – ident: 3886_CR1 – volume: 1 start-page: 1 year: 2008 ident: 3886_CR15 publication-title: J Ovarian Res doi: 10.1186/1757-2215-1-9 – volume: 24 start-page: 125 year: 2009 ident: 3886_CR16 publication-title: J Med Coll PLA doi: 10.1016/S1000-1948(09)60028-9 – volume: 75 start-page: 126 issue: 1 year: 2002 ident: 3886_CR25 publication-title: Am J Clin Nutr doi: 10.1093/ajcn/75.1.126 – volume: 15 start-page: 673 issue: 6 year: 2009 ident: 3886_CR27 publication-title: J Altern Complement Med doi: 10.1089/acm.2008.0387 – volume: 26 start-page: 2013 issue: 12 year: 2008 ident: 3886_CR26 publication-title: J Clin Oncol doi: 10.1200/JCO.2007.14.9930 – volume: 12 start-page: 1213 issue: 11 Pt 1 year: 2003 ident: 3886_CR22 publication-title: Cancer Epidemiol Biomarkers Prev – volume: 54 start-page: 3011 year: 1994 ident: 3886_CR14 publication-title: Cancer Res – volume: 49 start-page: 77 issue: 1 year: 2005 ident: 3886_CR28 publication-title: Lung Cancer doi: 10.1016/j.lungcan.2005.01.004 – volume: 84 start-page: 13 issue: 1 year: 1993 ident: 3886_CR7 publication-title: Jpn J Cancer Res doi: 10.1111/j.1349-7006.1993.tb02777.x – volume: 4 start-page: 995 issue: 5 year: 1997 ident: 3886_CR8 publication-title: Oncol Rep – volume: 48 start-page: 160 issue: 2 year: 2004 ident: 3886_CR23 publication-title: Nutr Cancer doi: 10.1207/s15327914nc4802_5 – volume: 32 start-page: 87 issue: 1 year: 2014 ident: 3886_CR29 publication-title: Investig New Drugs doi: 10.1007/s10637-013-9949-4 – volume: 6 start-page: 408 issue: 4 year: 2015 ident: 3886_CR12 publication-title: Adv Nutr doi: 10.3945/an.114.008052 |
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Epidemiologic and preclinical data suggest isoflavones have anticancer activity in colorectal malignancy prevention and treatment. This is the first... Epidemiologic and preclinical data suggest isoflavones have anticancer activity in colorectal malignancy prevention and treatment. This is the first clinical... BackgroundEpidemiologic and preclinical data suggest isoflavones have anticancer activity in colorectal malignancy prevention and treatment. This is the first... |
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| Title | Genistein combined with FOLFOX or FOLFOX–Bevacizumab for the treatment of metastatic colorectal cancer: phase I/II pilot study |
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