Randomised phase II trial of weekly ixabepilone ± biweekly bevacizumab for platinum-resistant or refractory ovarian/fallopian tube/primary peritoneal cancer

Dana M Roque, Eric R Siegel, Natalia Buza, Stefania Bellone, Dan-Arin Silasi, Gloria S Huang, Vaagn Andikyan, Mitchell Clark, Masoud Azodi, Peter E Schwartz, Gautam G Rao, Jocelyn C Reader, Pei Hui, Joan R Tymon-Rosario, Justin Harold, Dennis Mauricio, Burak Zeybek, Gulden Menderes, Gary Altwerger, Elena Ratner, Alessandro D Santin, Dana M Roque, Eric R Siegel, Natalia Buza, Stefania Bellone, Dan-Arin Silasi, Gloria S Huang, Vaagn Andikyan, Mitchell Clark, Masoud Azodi, Peter E Schwartz, Gautam G Rao, Jocelyn C Reader, Pei Hui, Joan R Tymon-Rosario, Justin Harold, Dennis Mauricio, Burak Zeybek, Gulden Menderes, Gary Altwerger, Elena Ratner, Alessandro D Santin

Abstract

Background: This multi-center RP2 study assessed activity/safety of ixabepilone + bevacizumab compared to ixabepilone in platinum-resistant/refractory ovarian/fallopian tube/primary peritoneal cancer. Additional objectives were to examine the role of prior bevacizumab and taxanes, and explore class III-ß-tubulin (TUBB3) as a predictive biomarker.

Methods: Participants were randomised to receive ixabepilone 20 mg/m2 days 1, 8, 15 with (IXA + BEV) or without (IXA) bevacizumab 10 mg/kg days 1, 15 every 28 days. Patients were stratified by prior BEV. The primary endpoint was PFS. OS, safety, and ORR served as secondary endpoints.

Results: Among 76 evaluable patients who received IXA + BEV (n = 39) compared to IXA (n = 37), the ORR was 33% (n = 13) versus 8% (n = 3)(P = 0.004), durable at 6 months in 37% (n = 14) and 3% (n = 1) (P < 0.001). BEV significantly improved PFS (median:5.5 vs 2.2 months, HR = 0.33, 95%CI 0.19-0.55, P < 0.001) and OS (median:10.0 vs 6.0 months, HR = 0.52, 95%CI 0.31-0.87, P = 0.006). Both regimens were well-tolerated. TUBB3 expression did not predict response. Subgroup analyses revealed minimal effect of prior BEV or taxane resistant/refractory status on response to IXA + BEV.

Conclusions: IXA + BEV is a well-tolerated, effective combination for platinum/taxane-resistant ovarian cancer that extends PFS and likely OS relative to IXA monotherapy. Prior receipt of BEV should not preclude the use of IXA + BEV. TUBB3 is not a predictive biomarker.

Clinical trial registration: NCT3093155.

Trial registration: ClinicalTrials.gov NCT03093155.

Conflict of interest statement

The authors declare no competing interests.

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Figures

Fig. 1
Fig. 1
Consolidated Standards of Reporting Trials (CONSORT) diagram shows progress through randomization.
Fig. 2. Progression-free survival, overall survival, and…
Fig. 2. Progression-free survival, overall survival, and subgroup analyses.
a Progression-free survival: use of bevacizumab (BEV) with ixabepilone (IXA) significantly extended progression-free survival (5.5 vs 2.2 months, HR 0.33, 95% CI 0.19–0.55, p < 0.001) compared to IXA alone. b Overall Survival: overall survival was significantly longer in patients who received BEV in conjunction wiht IXA (10.0 vs 6.0 months, HR 0.52, 95% CI 0.31–0.87, p < 0.006). c Hazard ratios for progression-free survival versus treatment arm by subgroup: progression-free survival hazard radios were similar between arms among patients with prior BEV exposure (HR 0.36, 95% CI: 0.19–0.72, p = 0.003) and those who were BEV-naive (HR 0.27, 95%CI: 0.12–0.62, p = 0.002). Stratification by pre-treatment status, age, histology, and performance status are also shown. Error bars denote 95% confidence intervals (CI). d Hazard ratios for overall survival versus treatment arm by subgroup: similar hazard ratios for overall survival were observed between arms among patients with prior BEV exposure (HR 0.50, 95%: 0.25–1.02, p = 0.058) and those who were BEV-naive (HR 0.54, 95% CI: 0.24–1.22, p = 0.14). Stratification by pre-treatment status, age, histology, and performance status are also shown. Error bars denote 95% CI.

References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70:7–30. doi: 10.3322/caac.21590.
    1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018;68:394–424. doi: 10.3322/caac.21492.
    1. Jayson GC, Kohn EC, Kitchener HC, Ledermann JA. Ovarian cancer. Lancet. 2014;384:1376–88. doi: 10.1016/S0140-6736(13)62146-7.
    1. Pujade-Lauraine E, Hilpert F, Weber B, Reuss A, Poveda A, Kristensen G, et al. Bevacizumab combined with chemotherapy for platinum-resistant recurrent ovarian cancer: the AURELIA open-label randomized phase III trial. J Clin Oncol. 2014;32:1302–8. doi: 10.1200/JCO.2013.51.4489.
    1. Wysham WZ, Schaffer EM, Coles T, Roque DR, Wheeler SB, Kim KH. Adding bevacizumab to single agent chemotherapy for the treatment of platinum-resistant recurrent ovarian cancer: a cost effectiveness analysis of the AURELIA trial. Gynecol Oncol. 2017;145:340–5. doi: 10.1016/j.ygyno.2017.02.039.
    1. McDaid HM, Mani S, Shen H-J, Muggia F, Sonnichsen D, Horwitz SB. Validation of the pharmacodynamics of BMS-247550, an analogue of epothilone B, during a phase I clinical study. Clin Cancer Res. 2002;8:2035–43.
    1. Shemesh OA, Spira ME. Paclitaxel induces axonal microtubules polar reconfiguration and impaired organelle transport: implications for the pathogenesis of paclitaxel-induced polyneuropathy. Acta Neuropathol. 2010;119:235–48. doi: 10.1007/s00401-009-0586-0.
    1. De Geest K, Blessing JA, Morris RT, Yamada SD, Monk BJ, Zweizig SL, et al. Phase II clinical trial of ixabepilone in patients with recurrent or persistent platinum- and taxane-resistant ovarian or primary peritoneal cancer: a gynecologic oncology group study. J Clin Oncol. 2010;28:149–53. doi: 10.1200/JCO.2009.24.1455.
    1. Thomas ES, Gomez HL, Li RK, Chung H-C, Fein LE, Chan VF, et al. Ixabepilone plus capecitabine for metastatic breast cancer progressing after anthracycline and taxane treatment. J Clin Oncol. 2007;25:5210–7. doi: 10.1200/JCO.2007.12.6557.
    1. Sparano JA, Vrdoljak E, Rixe O, Xu B, Manikhas A, Medina C, et al. Randomized phase III trial of Ixabepilone plus capecitabine versus capecitabine in patients with metastatic breast cancer previously treated with an anthracycline and a taxane. J Clin Oncol. 2010;28:3256–63. doi: 10.1200/JCO.2009.24.4244.
    1. Rocha Lima CM, Lin EH, Kim GP, Giguere JK, Marshall J, Zalupski M, et al. A phase 2 trial of ixabepilone plus cetuximab in first-line treatment of metastatic pancreatic cancer. Gastrointest Cancer Res. 2012;5:155–60.
    1. Whitehead RP, McCoy S, Rivkin SE, Gross HM, Conrad ME, Doolittle GC, et al. A Phase II trial of epothilone B analogue BMS-247550 (NSC #710428) ixabepilone, in patients with advanced pancreas cancer: a southwest oncology group study. Invest N. Drugs. 2006;24:515–20. doi: 10.1007/s10637-006-8440-x.
    1. Edelman MJ, Schneider C-P, Tsai C-M, Kim H-T, Quoix E, Luft AV, et al. Randomized phase II study of ixabepilone or paclitaxel plus carboplatin in patients with non-small-cell lung cancer prospectively stratified by beta-3 tubulin status. J Clin Oncol. 2013;31:1990–6. doi: 10.1200/JCO.2012.45.3282.
    1. Rosenberg JE, Weinberg VK, Kelly WK, Michaelson D, Hussain MH, Wilding G, et al. Activity of second-line chemotherapy in docetaxel-refractory hormone-refractory prostate cancer patients: randomized phase 2 study of ixabepilone or mitoxantrone and prednisone. Cancer. 2007;110:556–63. doi: 10.1002/cncr.22811.
    1. Liu G, Chen Y-H, Dipaola R, Carducci M, Wilding G. Phase II trial of weekly ixabepilone in men with metastatic castrate-resistant prostate cancer (E3803): a trial of the Eastern Cooperative Oncology Group. Clin Genitourin Cancer. 2012;10:99–105. doi: 10.1016/j.clgc.2012.01.009.
    1. FDA Approval for Ixabepilone. 2016; .
    1. Roque DM, Ratner ES, Silasi D-A, Azodi M, Rutherford TJ, Schwartz PE, et al. Weekly ixabepilone with or without biweekly bevacizumab in the treatment of recurrent or persistent uterine and ovarian/primary peritoneal/fallopian tube cancers: a retrospective review. Gynecol Oncol. 2015;137:392–400. doi: 10.1016/j.ygyno.2015.03.008.
    1. Lee FYF, Borzilleri R, Fairchild CR, Kamath A, Smykla R, Kramer R, et al. Preclinical discovery of ixabepilone, a highly active antineoplastic agent. Cancer Chemother Pharm. 2008;63:157–66. doi: 10.1007/s00280-008-0724-8.
    1. Mozzetti S, Ferlini C, Concolino P, Filippetti F, Raspaglio G, Prislei S, et al. Class III beta-tubulin overexpression is a prominent mechanism of paclitaxel resistance in ovarian cancer patients. Clin Cancer Res. 2005;11:298–305. doi: 10.1158/1078-0432.298.11.1.
    1. Ferrandina G, Zannoni GF, Martinelli E, Paglia A, Gallotta V, Mozzetti S, et al. Class III beta-tubulin overexpression is a marker of poor clinical outcome in advanced ovarian cancer patients. Clin Cancer Res. 2006;12:2774–9. doi: 10.1158/1078-0432.CCR-05-2715.
    1. Roque DM, Buza N, Glasgow M, Bellone S, Bortolomai I, Gasparrini S, et al. Class III β-tubulin overexpression within the tumor microenvironment is a prognostic biomarker for poor overall survival in ovarian cancer patients treated with neoadjuvant carboplatin/paclitaxel. Clin Exp Metastasis. 2014;31:101–10. doi: 10.1007/s10585-013-9614-5.
    1. Roque DM, Bellone S, Buza N, Romani C, Cocco E, Bignotti E, et al. Class III β-tubulin overexpression in ovarian clear cell and serous carcinoma as a maker for poor overall survival after platinum/taxane chemotherapy and sensitivity to patupilone. Am J Obstet Gynecol. 2013;209:62.e1–9. doi: 10.1016/j.ajog.2013.04.017.
    1. Hayashi Y, Kuriyama H, Umezu H, Tanaka J, Yoshimasu T, Furukawa T, et al. Class III beta-tubulin expression in tumor cells is correlated with resistance to docetaxel in patients with completely resected non-small-cell lung cancer. Intern Med. 2009;48:203–8. doi: 10.2169/internalmedicine.48.1659.
    1. Li Z, Qing Y, Guan W, Li M, Peng Y, Zhang S, et al. Predictive value of APE1, BRCA1, ERCC1 and TUBB3 expression in patients with advanced non-small cell lung cancer (NSCLC) receiving first-line platinum-paclitaxel chemotherapy. Cancer Chemother Pharm. 2014;74:777–86. doi: 10.1007/s00280-014-2562-1.
    1. Verschraegen CF, Sittisomwong T, Kudelka AP, Guedes ED, Steger M, Nelson-Taylor T, et al. Docetaxel for patients with paclitaxel-resistant Müllerian carcinoma. J Clin Oncol. 2000;18:2733–9. doi: 10.1200/JCO.2000.18.14.2733.
    1. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45:228–47. doi: 10.1016/j.ejca.2008.10.026.
    1. Oken MM, Creech RH, Tormey DC, Horton J, Davis TE, McFadden ET, et al. Toxicity and response criteria of the Eastern Cooperative Oncology Group. Am J Clin Oncol. 1982;5:649–55. doi: 10.1097/00000421-198212000-00014.
    1. Roque DM, Bellone S, English DP, Buza N, Cocco E, Gasparrini S, et al. Tubulin-β-III overexpression by uterine serous carcinomas is a marker for poor overall survival after platinum/taxane chemotherapy and sensitivity to epothilones. Cancer. 2013;119:2582–92. doi: 10.1002/cncr.28017.
    1. Katsumata N, Yasuda M, Takahashi F, Isonishi S, Jobo T, Aoki D, et al. Dose-dense paclitaxel once a week in combination with carboplatin every 3 weeks for advanced ovarian cancer: a phase 3, open-label, randomised controlled trial. Lancet. 2009;374:1331–8. doi: 10.1016/S0140-6736(09)61157-0.
    1. Seidman AD, Berry D, Cirrincione C, Harris L, Muss H, Marcom PK, et al. Randomized phase III trial of weekly compared with every-3-weeks paclitaxel for metastatic breast cancer, with trastuzumab for all HER-2 overexpressors and random assignment to trastuzumab or not in HER-2 nonoverexpressors: final results of Cancer and Leukemia Group B protocol 9840. J Clin Oncol. 2008;26:1642–9. doi: 10.1200/JCO.2007.11.6699.
    1. Fountzilas G, Kotoula V, Pectasides D, Kouvatseas G, Timotheadou E, Bobos M, et al. Ixabepilone administered weekly or every three weeks in HER2-negative metastatic breast cancer patients; a randomized non-comparative phase II trial. PLoS ONE. 2013;8:e69256. doi: 10.1371/journal.pone.0069256.
    1. Awada A, Piccart MJ, Jones SF, Peck RA, Gil T, Lebwohl D, et al. Phase I dose escalation study of weekly ixabepilone, an epothilone analog, in patients with advanced solid tumors who have failed standard therapy. Cancer Chemother Pharm. 2009;63:417–25. doi: 10.1007/s00280-008-0751-5.
    1. Common Terminology Criteria for Adverse Events (CTCAE) | Protocol Development | CTEP. 2020; .
    1. Burger RA, Brady MF, Bookman MA, Fleming GF, Monk BJ, Huang H, et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N. Engl J Med. 2011;365:2473–83. doi: 10.1056/NEJMoa1104390.
    1. Oza AM, Cook AD, Pfisterer J, Embleton A, Ledermann JA, Pujade-Lauraine E, et al. Standard chemotherapy with or without bevacizumab for women with newly diagnosed ovarian cancer (ICON7): overall survival results of a phase 3 randomised trial. Lancet Oncol. 2015;16:928–36. doi: 10.1016/S1470-2045(15)00086-8.
    1. Aghajanian C, Goff B, Nycum LR, Wang YV, Husain A, Blank SV. Final overall survival and safety analysis of OCEANS, a phase 3 trial of chemotherapy with or without bevacizumab in patients with platinum-sensitive recurrent ovarian cancer. Gynecol Oncol. 2015;139:10–6. doi: 10.1016/j.ygyno.2015.08.004.
    1. Coleman RL, Brady MF, Herzog TJ, Sabbatini P, Armstrong DK, Walker JL, et al. Bevacizumab and paclitaxel-carboplatin chemotherapy and secondary cytoreduction in recurrent, platinum-sensitive ovarian cancer (NRG Oncology/Gynecologic Oncology Group study GOG-0213): a multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2017;18:779–91. doi: 10.1016/S1470-2045(17)30279-6.
    1. Bamias A, Gibbs E, Khoon Lee C, Davies L, Dimopoulos M, Zagouri F, et al. Bevacizumab with or after chemotherapy for platinum-resistant recurrent ovarian cancer: exploratory analyses of the AURELIA trial. Ann Oncol. 2017;28:1842–8. doi: 10.1093/annonc/mdx228.
    1. Colombo N, Kutarska E, Dimopoulos M, Bae D-S, Rzepka-Gorska I, Bidzinski M, et al. Randomized, open-label, phase III study comparing patupilone (EPO906) with pegylated liposomal doxorubicin in platinum-refractory or -resistant patients with recurrent epithelial ovarian, primary fallopian tube, or primary peritoneal cancer. J Clin Oncol. 2012;30:3841–7. doi: 10.1200/JCO.2011.38.8082.
    1. Lee JJ, Swain SM. The epothilones: translating from the laboratory to the clinic. Clin Cancer Res. 2008;14:1618–24. doi: 10.1158/1078-0432.CCR-07-2201.
    1. Vansteenkiste J, Lara PN, Le Chevalier T, Breton J-L, Bonomi P, Sandler AB, et al. Phase II clinical trial of the epothilone B analog, ixabepilone, in patients with non small-cell lung cancer whose tumors have failed first-line platinum-based chemotherapy. J Clin Oncol. 2007;25:3448–55. doi: 10.1200/JCO.2006.09.7097.
    1. Huang H, Menefee M, Edgerly M, Zhuang S, Kotz H, Poruchynsky M, et al. A phase II clinical trial of ixabepilone (Ixempra; BMS-247550; NSC 710428), an epothilone B analog, in patients with metastatic renal cell carcinoma. Clin Cancer Res. 2010;16:1634–41. doi: 10.1158/1078-0432.CCR-09-0379.
    1. Dreicer R, Li S, Manola J, Haas NB, Roth BJ, Wilding G, et al. Phase 2 trial of epothilone B analog BMS-247550 (ixabepilone) in advanced carcinoma of the urothelium (E3800): a trial of the Eastern Cooperative Oncology Group. Cancer. 2007;110:759–63. doi: 10.1002/cncr.22839.
    1. Low JA, Wedam SB, Lee JJ, Berman AW, Brufsky A, Yang SX, et al. Phase II clinical trial of ixabepilone (BMS-247550), an epothilone B analog, in metastatic and locally advanced breast cancer. J Clin Oncol. 2005;23:2726–34. doi: 10.1200/JCO.2005.10.024.
    1. Poveda AM, Selle F, Hilpert F, Reuss A, Savarese A, Vergote I, et al. Bevacizumab combined with weekly paclitaxel, pegylated liposomal doxorubicin, or topotecan in platinum-resistant recurrent ovarian cancer: analysis by chemotherapy cohort of the randomized phase III AURELIA trial. J Clin Oncol. 2015;33:3836–8. 10.1200/JCO.2015.63.1408.
    1. O’Malley DM, Richardson DL, Rheaume PS, Salani R, Eisenhauer EL, McCann GA, et al. Addition of bevacizumab to weekly paclitaxel significantly improves progression-free survival in heavily pretreated recurrent epithelial ovarian cancer. Gynecol Oncol. 2011;121:269–72. doi: 10.1016/j.ygyno.2011.01.009.
    1. Gynecologic Oncology Group. Markman M, Blessing J, Rubin SC, Connor J, Hanjani P, et al. Phase II trial of weekly paclitaxel (80 mg/m2) in platinum and paclitaxel-resistant ovarian and primary peritoneal cancers: a Gynecologic Oncology Group study. Gynecol Oncol. 2006;101:436–40. doi: 10.1016/j.ygyno.2005.10.036.
    1. Burger RA, Sill MW, Monk BJ, Greer BE, Sorosky JI. Phase II trial of bevacizumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group Study. J Clin Oncol. 2007;25:5165–71. doi: 10.1200/JCO.2007.11.5345.
    1. Shintani D, Yoshida H, Yabuno A, Fujiwara K. Tolerability and efficacy of bevacizumab monotherapy in older patients with recurrent ovarian cancer. Vivo. 2020;34:1451–7. doi: 10.21873/invivo.11928.
    1. Cannistra SA, Matulonis UA, Penson RT, Hambleton J, Dupont J, Mackey H, et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. JCO. 2007;25:5180–6. doi: 10.1200/JCO.2007.12.0782.
    1. Lee FYF, Covello KL, Castaneda S, Hawken DR, Kan D, Lewin A, et al. Synergistic antitumor activity of ixabepilone (BMS-247550) plus bevacizumab in multiple in vivo tumor models. Clin Cancer Res. 2008;14:8123–31. doi: 10.1158/1078-0432.CCR-08-0025.
    1. Woltering EA, Lewis JM, Maxwell PJ, Frey DJ, Wang Y-Z, Rothermel J, et al. Development of a novel in vitro human tissue-based angiogenesis assay to evaluate the effect of antiangiogenic drugs. Ann Surg. 2003;237:790–8.
    1. Bijman MNA, van Nieuw Amerongen GP, Laurens N, van Hinsbergh VWM, Boven E. Microtubule-targeting agents inhibit angiogenesis at subtoxic concentrations, a process associated with inhibition of Rac1 and Cdc42 activity and changes in the endothelial cytoskeleton. Mol Cancer Ther. 2006;5:2348–57. doi: 10.1158/1535-7163.MCT-06-0242.
    1. Lau DH, Xue L, Young LJ, Burke PA, Cheung AT. Paclitaxel (Taxol): an inhibitor of angiogenesis in a highly vascularized transgenic breast cancer. Cancer Biother Radiopharm. 1999;14:31–6. doi: 10.1089/cbr.1999.14.31.
    1. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science. 2005;307:58–62. doi: 10.1126/science.1104819.
    1. Qi W-X, Shen Z, Tang L-N, Yao Y. Bevacizumab increases the risk of gastrointestinal perforation in cancer patients: a meta-analysis with a focus on different subgroups. Eur J Clin Pharm. 2014;70:893–906. doi: 10.1007/s00228-014-1687-9.
    1. Robert NJ, Diéras V, Glaspy J, Brufsky AM, Bondarenko I, Lipatov ON, et al. RIBBON-1: randomized, double-blind, placebo-controlled, phase III trial of chemotherapy with or without bevacizumab for first-line treatment of human epidermal growth factor receptor 2-negative, locally recurrent or metastatic breast cancer. J Clin Oncol. 2011;29:1252–60. doi: 10.1200/JCO.2010.28.0982.
    1. Tomao F, Tomao S, Benedetti, Panici P. Combination of bevacizumab and chemotherapy for platinum-resistant recurrent ovarian cancer: some observations about the AURELIA trial. J Clin Oncol. 2014;32:3580. doi: 10.1200/JCO.2014.57.6231.
    1. Matsuoka A, Maeda O, Mizutani T, Nakano Y, Tsunoda N, Kikumori T, et al. Bevacizumab Exacerbates Paclitaxel-Induced Neuropathy: A Retrospective Cohort Study. PLoS ONE. 2016;11:e0168707. doi: 10.1371/journal.pone.0168707.
    1. Tamura R, Tanaka T, Miyake K, Yoshida K, Sasaki H. Bevacizumab for malignant gliomas: current indications, mechanisms of action and resistance, and markers of response. Brain Tumor Pathol. 2017;34:62–77. doi: 10.1007/s10014-017-0284-x.
    1. Wang S, Xiao Z, Hong Z, Jiao H, Zhu S, Zhao Y, et al. FOXF1 promotes angiogenesis and accelerates bevacizumab resistance in colorectal cancer by transcriptionally activating VEGFA. Cancer Lett. 2018;28:78–90. doi: 10.1016/j.canlet.2018.09.026.
    1. Li L, Nan F, Guo Q, Guan D, Zhou C. Resistance to bevacizumab in ovarian cancer SKOV3 xenograft due to EphB4 overexpression. J Cancer Res Ther. 2019;15:1282–7. doi: 10.4103/0973-1482.204896.
    1. Guerrouahen BS, Pasquier J, Kaoud NA, Maleki M, Beauchamp M-C, Yasmeen A, et al. Akt-activated endothelium constitutes the niche for residual disease and resistance to bevacizumab in ovarian cancer. Mol Cancer Ther. 2014;13:3123–36. doi: 10.1158/1535-7163.MCT-13-1053.
    1. Deng Z, Zhou J, Han X, Li X. TCEB2 confers resistance to VEGF-targeted therapy in ovarian cancer. Oncol Rep. 2016;35:359–65. doi: 10.3892/or.2015.4388.
    1. Eriksson JA, Wanka C, Burger MC, Urban H, Hartel I, von Renesse J, et al. Suppression of oxidative phosphorylation confers resistance against bevacizumab in experimental glioma. J Neurochem. 2018;144:421–30. doi: 10.1111/jnc.14264.
    1. McCann GA, Smith B, Backes FJ, Rath K, Chacko S, Salani R, et al. Recurrent ovarian cancer: is there a role for re-treatment with bevacizumab after an initial complete response to a bevacizumab-containing regimen? Gynecol Oncol. 2012;127:362–6. doi: 10.1016/j.ygyno.2012.08.001.
    1. Laskey RA, Richard SD, Smith AL, Lin JF, Beck TL, Lesnock JL, et al. Retreatment with bevacizumab in patients with gynecologic malignancy is associated with clinical response and does not increase morbidity. Onco Targets Ther. 2014;7:469–76. doi: 10.2147/OTT.S57425.
    1. Pfisterer J, Shannon CM, Baumann K, Rau J, Harter P, Joly F, et al. Bevacizumab and platinum-based combinations for recurrent ovarian cancer: a randomised, open-label, phase 3 trial. Lancet Oncol. 2020;21:699–709. doi: 10.1016/S1470-2045(20)30142-X.
    1. Pignata S, Lorusso D, Joly F, Gallo C, Colombo N, Sessa C, et al. Chemotherapy plus or minus bevacizumab for platinum-sensitive ovarian cancer patients recurring after a bevacizumab containing first line treatment: The randomized phase 3 trial MITO16B-MaNGO OV2B-ENGOT OV17. JCO. 2018;36:5506–5506. doi: 10.1200/JCO.2018.36.15_suppl.5506.
    1. Davio K. Amgen and Allergan Launch Mvasi and Kanjinti, the First Anticancer Biosimilars, in the United States. 2020; .
    1. McPherson A, Roth A, Laks E, Masud T, Bashashati A, Zhang AW, et al. Divergent modes of clonal spread and intraperitoneal mixing in high-grade serous ovarian cancer. Nat Genet. 2016;48:758–67. doi: 10.1038/ng.3573.
    1. Bordji K, Grandval A, Cuhna-Alves L, Lechapt-Zalcman E, Bernaudin M.Hypoxia-inducible factor-2α (HIF-2α), but not HIF-1α, is essential for hypoxic induction of class III β-tubulin expression in human glioblastoma cells. FEBS J. 2014;281:5220–36.
    1. Raspaglio G, Filippetti F, Prislei S, Penci R, De Maria I, Cicchillitti L, et al. Hypoxia induces class III beta-tubulin gene expression by HIF-1alpha binding to its 3’ flanking region. Gene. 2008;409:100–8. doi: 10.1016/j.gene.2007.11.015.
    1. Izutsu N, Maesawa C, Shibazaki M, Oikawa H, Shoji T, Sugiyama T, et al. Epigenetic modification is involved in aberrant expression of class III beta-tubulin, TUBB3, in ovarian cancer cells. Int J Oncol. 2008;32:1227–35.
    1. Xie S, Ogden A, Aneja R, Zhou J. Microtubule-binding proteins as promising biomarkers of paclitaxel sensitivity in cancer chemotherapy. Med Res Rev. 2016;36:300–12. doi: 10.1002/med.21378.
    1. Rouzier R, Rajan R, Wagner P, Hess KR, Gold DL, Stec J, et al. Microtubule-associated protein tau: a marker of paclitaxel sensitivity in breast cancer. Proc Natl Acad Sci USA. 2005;102:8315–20. doi: 10.1073/pnas.0408974102.
    1. Gurler H, Yu Y, Choi J, Kajdacsy-Balla AA, Barbolina MV. Three-dimensional collagen type I matrix up-regulates nuclear isoforms of the microtubule associated protein tau implicated in resistance to paclitaxel therapy in ovarian carcinoma. Int J Mol Sci. 2015;16:3419–33. doi: 10.3390/ijms16023419.
    1. Thomas GE, Sreeja JS, Gireesh KK, Gupta H, Manna TK. +TIP EB1 downregulates paclitaxel‑induced proliferation inhibition and apoptosis in breast cancer cells through inhibition of paclitaxel binding on microtubules. Int J Oncol. 2015;46:133–46. doi: 10.3892/ijo.2014.2701.
    1. Su D, Smith SM, Preti M, Schwartz P, Rutherford TJ, Menato G, et al. Stathmin and tubulin expression and survival of ovarian cancer patients receiving platinum treatment with and without paclitaxel. Cancer. 2009;115:2453–63. doi: 10.1002/cncr.24282.
    1. LaPointe NE, Morfini G, Brady ST, Feinstein SC, Wilson L, Jordan MA. Effects of eribulin, vincristine, paclitaxel and ixabepilone on fast axonal transport and kinesin-1 driven microtubule gliding: implications for chemotherapy-induced peripheral neuropathy. Neurotoxicology. 2013;37:231–9. doi: 10.1016/j.neuro.2013.05.008.

Source: PubMed

Sponsoren und Mitarbeiter

Krankheiten

Drogeninterventionen

3
Abonnieren