Generic placeholder image

Current Cancer Therapy Reviews

Editor-in-Chief

ISSN (Print): 1573-3947
ISSN (Online): 1875-6301

Systematic Review Article

Adverse Effects and Safety of Etirinotecan Pegol, a Novel Topoisomerase Inhibitor, in Cancer Treatment: A Systematic Review

Author(s): Mohammad Samare-Najaf, Ali Samareh, Navid Jamali, Ali Abbasi, Cain C.T. Clark, Majid J. Khorchani and Fatemeh Zal*

Volume 17, Issue 3, 2021

Published on: 01 February, 2021

Page: [234 - 243] Pages: 10

DOI: 10.2174/1573394717666210202103502

Price: $65

Abstract

Background: Due to the increasing prevalence of cancer and the inadequacy of current therapies, the development of novel antitumor pharmaceutics with higher efficacies and lower adverse effects is considered a fundamental tenet of contemporary cancer management. Poly-Ethylene-Glycol (PEG) attachment is a novel pharmaceutical technology to improve the efficacy and safety of chemotherapies. Etirinotecan Pegol (EP), also known as NKTR-102, is the PEGylated form of Irinotecan (CPT-11), which causes cancer cell apoptosis by inhibiting the topoisomerase I enzyme.

Objective: The present study reviews and evaluates various reports of the EP’s anti-tumor activity in various cancers.

Data Source: Studies were identified using the Scopus database, with no exclusions. The search terms included Etirinotecan Pegol and NKTR-102, which yielded 125 articles (66 and 59 articles, respectively). In addition, the clinicaltrials.gov website was used to find ongoing studies, which resulted in the addition of two studies.

Study Eligibility Criteria: Subsequently, we excluded studies that were published in languages other than English, duplicate articles, and studies with no data.

Results: This systematic review clarifies that EP possesses numerous advantages over many other medications, such as safety, efficacy, increased half-life, increased health-related quality of life, increased overall survival, increased progression-free survival, and decreasing the adverse events in the treatment of various cancers.

Conclusion: Therefore, Etirinotecan Pegol may represent a major contribution to the treatment of various cancers in the future.

Keywords: Cancer, chemotherapy, drug safety, toxicology, clinical trials, topoisomerase inhibitors.

Graphical Abstract

[1]
Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA Cancer J Clin 2017; 67(1): 7-30.
[http://dx.doi.org/10.3322/caac.21387] [PMID: 28055103]
[2]
Uzunalli G, Dieterly AM, Kemet CM, et al. Dynamic transition of the blood-brain barrier in the development of non-small cell lung cancer brain metastases. Oncotarget 2019; 10(59): 6334-48.
[http://dx.doi.org/10.18632/oncotarget.27274] [PMID: 31695842]
[3]
Abbasi A, Movahedpour A, Amiri A, Najaf MS, Mostafavi-Pour Z. Darolutamide as a second-generation Androgen receptor inhibitor in the treatment of prostate cancer. Curr Mol Med 2021; 21(4): 332-46.
[http://dx.doi.org/10.2174/1566524020666200903120344] [PMID: 32881669]
[4]
De Nunzio C, Presicce F, Lombardo R, et al. Physical activity as A risk factor for prostate cancer diagnosis: a prospective biopsy cohort analysis. BJU Int 2016; 117(6B): E29-35.
[http://dx.doi.org/10.1111/bju.13157] [PMID: 25908534]
[5]
Prabhakar P, Punnaveetil S. Early detection and screening of cancer. In: Bioactive Components, Diet and Medical Treatment in Cancer Prevention. Springer 2018; pp. 149-60.
[http://dx.doi.org/10.1007/978-3-319-75693-6_13]
[6]
Khalil DN, Smith EL, Brentjens RJ, Wolchok JD. The future of cancer treatment: Immunomodulation, CARs and combination immunotherapy. Nat Rev Clin Oncol 2016; 13(5): 273-90.
[http://dx.doi.org/10.1038/nrclinonc.2016.25] [PMID: 26977780]
[7]
Durie BGM, Hoering A, Abidi MH, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 2017; 389(10068): 519-27.
[http://dx.doi.org/10.1016/S0140-6736(16)31594-X] [PMID: 28017406]
[8]
Adams JU. Genetics: Big hopes for big data. Nature 2015; 527(7578): S108-9.
[http://dx.doi.org/10.1038/527S108a] [PMID: 26580158]
[9]
Estanqueiro M, Amaral MH, Conceição J, Sousa Lobo JM. Nanotechnological carriers for cancer chemotherapy: The state of the art. Colloids Surf B Biointerfaces 2015; 126: 631-48.
[http://dx.doi.org/10.1016/j.colsurfb.2014.12.041] [PMID: 25591851]
[10]
Shinde A, Wilmanski T, Chen H, Teegarden D, Wendt MK. Pyruvate carboxylase supports the pulmonary tropism of metastatic breast cancer. Breast Cancer Res 2018; 20(1): 76.
[http://dx.doi.org/10.1186/s13058-018-1008-9] [PMID: 30005601]
[11]
Shinde A, Paez JS, Libring S, Hopkins K, Solorio L, Wendt MK. Transglutaminase-2 facilitates extracellular vesicle-mediated establishment of the metastatic niche. Oncogenesis 2020; 9(2): 16.
[http://dx.doi.org/10.1038/s41389-020-0204-5] [PMID: 32054828]
[12]
Libring S, Shinde A, Chanda MK, et al. The dynamic relationship of breast cancer cells and fibroblasts in fibronectin accumulation at primary and metastatic tumor sites. Cancers (Basel) 2020; 12(5): 1270.
[http://dx.doi.org/10.3390/cancers12051270] [PMID: 32429591]
[13]
Kitao H, Iimori M, Kataoka Y, et al. DNA replication stress and cancer chemotherapy. Cancer Sci 2018; 109(2): 264-71.
[http://dx.doi.org/10.1111/cas.13455] [PMID: 29168596]
[14]
Samare-Najaf M, Zal F, Safari S. Primary and secondary markers of doxorubicin-induced female infertility and the alleviative properties of quercetin and vitamin E in a rat model. Reprod Toxicol 2020; 96: 316-26.
[http://dx.doi.org/10.1016/j.reprotox.2020.07.015] [PMID: 32810592]
[15]
Wilmanski T, Zhou X, Zheng W, et al. Inhibition of pyruvate carboxylase by 1α,25-dihydroxyvitamin D promotes oxidative stress in early breast cancer progression. Cancer Lett 2017; 411: 171-81.
[http://dx.doi.org/10.1016/j.canlet.2017.09.045] [PMID: 29024812]
[16]
Shinde A, Hardy SD, Kim D, et al. Spleen tyrosine kinase–mediated autophagy is required for epithelial–mesenchymal plasticity and metastasis in breast cancer. Cancer Res 2019; 79(8): 1831-43.
[http://dx.doi.org/10.1158/0008-5472.CAN-18-2636] [PMID: 30733195]
[17]
Shinde A, Libring S, Alpsoy A, et al. Autocrine fibronectin inhibits breast cancer metastasis. Mol Cancer Res 2018; 16(10): 1579-89.
[http://dx.doi.org/10.1158/1541-7786.MCR-18-0151] [PMID: 29934326]
[18]
Chen S-F, Huang N-L, Lin J-H, et al. Structural insights into the gating of DNA passage by the topoisomerase II DNA-gate. Nat Commun 2018; 9(1): 3085.
[http://dx.doi.org/10.1038/s41467-018-05406-y] [PMID: 30082834]
[19]
Pommier Y, Sun Y, Huang SN, Nitiss JL. Roles of eukaryotic topoisomerases in transcription, replication and genomic stability. Nat Rev Mol Cell Biol 2016; 17(11): 703-21.
[http://dx.doi.org/10.1038/nrm.2016.111] [PMID: 27649880]
[20]
Danhier F. To exploit the tumor microenvironment: Since the EPR effect fails in the clinic, what is the future of nanomedicine? J Control Release 2016; 244(Pt 4): 108-21.
[http://dx.doi.org/10.1016/j.jconrel.2016.11.015] [PMID: 27871992]
[21]
Kummar S, Chen A, Gutierrez M, et al. Clinical and pharmacologic evaluation of two dosing schedules of indotecan (LMP400), a novel indenoisoquinoline, in patients with advanced solid tumors. Cancer Chemother Pharmacol 2016; 78(1): 73-81.
[http://dx.doi.org/10.1007/s00280-016-2998-6] [PMID: 27169793]
[22]
Oberlies NH, Kroll DJ. Camptothecin and taxol: Historic achievements in natural products research. J Nat Prod 2004; 67(2): 129-35.
[http://dx.doi.org/10.1021/np030498t] [PMID: 14987046]
[23]
Svenson S, Wolfgang M, Hwang J, Ryan J, Eliasof S. Preclinical to clinical development of the novel camptothecin nanopharmaceutical CRLX101. J Control Release 2011; 153(1): 49-55.
[http://dx.doi.org/10.1016/j.jconrel.2011.03.007] [PMID: 21406204]
[24]
Rowinsky EK, Grochow LB, Hendricks CB, et al. Phase I and pharmacologic study of topotecan: a novel topoisomerase I inhibitor. J Clin Oncol 1992; 10(4): 647-56.
[http://dx.doi.org/10.1200/JCO.1992.10.4.647] [PMID: 1312588]
[25]
Creemers GJ, Bolis G, Gore M, et al. Topotecan, an active drug in the second-line treatment of epithelial ovarian cancer: Results of a large European phase II study. J Clin Oncol 1996; 14(12): 3056-61.
[http://dx.doi.org/10.1200/JCO.1996.14.12.3056] [PMID: 8955650]
[26]
Gordon AN, Fleagle JT, Guthrie D, Parkin DE, Gore ME, Lacave AJ. Recurrent epithelial ovarian carcinoma: A randomized phase III study of pegylated liposomal doxorubicin versus topotecan. J Clin Oncol 2001; 19(14): 3312-22.
[http://dx.doi.org/10.1200/JCO.2001.19.14.3312] [PMID: 11454878]
[27]
Lin NU, Eierman W, Greil R, et al. Randomized phase II study of lapatinib plus capecitabine or lapatinib plus topotecan for patients with HER2-positive breast cancer brain metastases. J Neurooncol 2011; 105(3): 613-20.
[http://dx.doi.org/10.1007/s11060-011-0629-y] [PMID: 21706359]
[28]
Bramwell VH, Eisenhauer EA, Blackstein M, et al. Phase II study of topotecan (NSC 609 699) in patients with recurrent or metastatic soft tissue sarcoma. Ann Oncol 1995; 6(8): 847-9.
[http://dx.doi.org/10.1093/oxfordjournals.annonc.a059329] [PMID: 8589028]
[29]
Creemers GJ, Gerrits CJ, Schellens JH, et al. Phase II and pharmacologic study of topotecan administered as a 21-day continuous infusion to patients with colorectal cancer. J Clin Oncol 1996; 14(9): 2540-5. Available from: https://pubmed.ncbi.nlm.nih.gov/8823333/
[http://dx.doi.org/10.1200/JCO.1996.14.9.2540] [PMID: 8823333]
[30]
Robert F, Soong SJ, Wheeler RH. A phase II study of topotecan in patients with recurrent head and neck cancer. Identification of an active new agent. Am J Clin Oncol 1997; 20(3): 298-302.
[http://dx.doi.org/10.1097/00000421-199706000-00019] [PMID: 9167758]
[31]
O’Brien ME, Ciuleanu T-E, Tsekov H, et al. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol 2006; 24(34): 5441-7.
[http://dx.doi.org/10.1200/JCO.2006.06.5821] [PMID: 17135646]
[32]
Schiller JH, Adak S, Cella D, DeVore RF III, Johnson DH. Topotecan versus observation after cisplatin plus etoposide in extensive-stage small-cell lung cancer: E7593-a phase III trial of the Eastern Cooperative Oncology Group. J Clin Oncol 2001; 19(8): 2114-22.
[http://dx.doi.org/10.1200/JCO.2001.19.8.2114] [PMID: 11304763]
[33]
Bookman MA, Blessing JA, Hanjani P, Herzog TJ, Andersen WA. Topotecan in squamous cell carcinoma of the cervix: A Phase II study of the Gynecologic Oncology Group. Gynecol Oncol 2000; 77(3): 446-9.
[http://dx.doi.org/10.1006/gyno.2000.5807] [PMID: 10831357]
[34]
Beran M, Kantarjian H, O’Brien S, et al. Topotecan, a topoisomerase I inhibitor, is active in the treatment of myelodysplastic syndrome and chronic myelomonocytic leukemia. Blood 1996; 88(7): 2473-9.
[http://dx.doi.org/10.1182/blood.V88.7.2473.bloodjournal8872473] [PMID: 8839838]
[35]
Cortes J, Kantarjian H, Albitar M, et al. A randomized trial of liposomal daunorubicin and cytarabine versus liposomal daunorubicin and topotecan with or without thalidomide as initial therapy for patients with poor prognosis acute myelogenous leukemia or myelodysplastic syndrome. Cancer 2003; 97(5): 1234-41.
[http://dx.doi.org/10.1002/cncr.11180] [PMID: 12599230]
[36]
Qazilbash MH, Saliba R, De Lima M, et al. Second autologous or allogeneic transplantation after the failure of first autograft in patients with multiple myeloma. Cancer 2006; 106(5): 1084-9.
[http://dx.doi.org/10.1002/cncr.21700] [PMID: 16456814]
[37]
Martino E, Della Volpe S, Terribile E, et al. The long story of camptothecin: From traditional medicine to drugs. Bioorg Med Chem Lett 2017; 27(4): 701-7.
[http://dx.doi.org/10.1016/j.bmcl.2016.12.085] [PMID: 28073672]
[38]
Chernov L, Deyell RJ, Anantha M, Dos Santos N, Gilabert-Oriol R, Bally MB. Optimization of liposomal topotecan for use in treating neuroblastoma. Cancer Med 2017; 6(6): 1240-54.
[http://dx.doi.org/10.1002/cam4.1083] [PMID: 28544814]
[39]
Kerklaan BM, Lolkema MP, Devriese LA, et al. Phase I and pharmacological study of pazopanib in combination with oral topotecan in patients with advanced solid tumours. Br J Cancer 2015; 113(5): 706-15.
[http://dx.doi.org/10.1038/bjc.2015.257] [PMID: 26291057]
[40]
Armstrong DK, Spriggs D, Levin J, Poulin R, Lane S. Hematologic safety and tolerability of topotecan in recurrent ovarian cancer and small cell lung cancer: an integrated analysis. Oncologist 2005; 10(9): 686-94.
[http://dx.doi.org/10.1634/theoncologist.10-9-686] [PMID: 16249347]
[41]
Curtis KK, Hartney JT, Jewell RC, et al. A phase I study to characterize the safety, tolerability, and pharmacokinetics of topotecan at 4 mg/m2 administered weekly as a 30-minute intravenous infusion in patients with cancer. J Clin Pharmacol 2010; 50(3): 268-75.
[http://dx.doi.org/10.1177/0091270009343699] [PMID: 19808951]
[42]
Eckardt JR, von Pawel J, Pujol J-L, et al. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol 2007; 25(15): 2086-92.
[http://dx.doi.org/10.1200/JCO.2006.08.3998] [PMID: 17513814]
[43]
Chabot GG. Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet 1997; 33(4): 245-59.
[http://dx.doi.org/10.2165/00003088-199733040-00001] [PMID: 9342501]
[44]
Douillard JY, Cunningham D, Roth AD, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first- line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 2000; 355(9209): 1041-7.
[http://dx.doi.org/10.1016/S0140-6736(00)02034-1] [PMID: 10744089]
[45]
Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 2004; 350(23): 2335-42.
[http://dx.doi.org/10.1056/NEJMoa032691] [PMID: 15175435]
[46]
Zou J, Li S, Chen Z, et al. A novel oral camptothecin analog, gimatecan, exhibits superior antitumor efficacy than irinotecan toward esophageal squamous cell carcinoma in vitro and in vivo. Cell Death Dis 2018; 9(6): 661.
[http://dx.doi.org/10.1038/s41419-018-0700-0] [PMID: 29855512]
[47]
Van Cutsem E, Sagaert X, Topal B, Haustermans K, Prenen H. Gastric cancer. Lancet 2016; 388(10060): 2654-64.
[http://dx.doi.org/10.1016/S0140-6736(16)30354-3] [PMID: 27156933]
[48]
Perez EA, Hillman DW, Mailliard JA, et al. Randomized phase II study of two irinotecan schedules for patients with metastatic breast cancer refractory to an anthracycline, a taxane, or both. J Clin Oncol 2004; 22(14): 2849-55.
[http://dx.doi.org/10.1200/JCO.2004.10.047] [PMID: 15254052]
[49]
Pfister DG, Johnson DH, Azzoli CG, et al. American Society of Clinical Oncology treatment of unresectable non-small-cell lung cancer guideline: update 2003. J Clin Oncol 2004; 22(2): 330-53.
[http://dx.doi.org/10.1200/JCO.2004.09.053] [PMID: 14691125]
[50]
Noda K, Nishiwaki Y, Kawahara M, et al. Japan Clinical Oncology Group. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med 2002; 346(2): 85-91.
[http://dx.doi.org/10.1056/NEJMoa003034] [PMID: 11784874]
[51]
Prados MD, Yung WK, Jaeckle KA, et al. North American Brain Tumor Consortium study. Phase 1 trial of irinotecan (CPT-11) in patients with recurrent malignant glioma: a North American Brain Tumor Consortium study. Neuro-oncol 2004; 6(1): 44-54.
[http://dx.doi.org/10.1215/S1152851703000292] [PMID: 14769140]
[52]
Meyer UA. Pharmacogenetics and adverse drug reactions. Lancet 2000; 356(9242): 1667-71.
[http://dx.doi.org/10.1016/S0140-6736(00)03167-6] [PMID: 11089838]
[53]
Rtibi K, Selmi S, Grami D, Sebai H, Amri M, Marzouki L. Irinotecan chemotherapy-induced intestinal oxidative stress: Underlying causes of disturbed mucosal water and electrolyte transport. Pathophysiology 2017; 24(4): 275-9.
[http://dx.doi.org/10.1016/j.pathophys.2017.07.002] [PMID: 28801072]
[54]
Deng C, Deng B, Jia L, et al. Preventive effects of a Chinese herbal formula, Shengjiang Xiexin Decoction, on irinotecan-induced delayed-onset diarrhea in rats. Evid Based Complement Alternat Med 2017; 2017: 7350251. Available from: https://pubmed.ncbi.nlm.nih.gov/28167974/
[http://dx.doi.org/10.1155/2017/7350251] [PMID: 28167974]
[55]
Landgraf MM, Bognar CLFB, Guerra RB, et al. Temporary dysarthria induced by irinotecan-case report of this rare adverse event. J Pharm Pharmacol 2017; 5: 636-41.
[56]
Smith NF, Figg WD, Sparreboom A. Pharmacogenetics of irinotecan metabolism and transport: an update. Toxicol In Vitro 2006; 20(2): 163-75.
[http://dx.doi.org/10.1016/j.tiv.2005.06.045] [PMID: 16271446]
[57]
Buck A, Halbritter S, Späth C, et al. Distribution and quantification of irinotecan and its active metabolite SN-38 in colon cancer murine model systems using MALDI MSI. Anal Bioanal Chem 2015; 407(8): 2107-16.
[http://dx.doi.org/10.1007/s00216-014-8237-2] [PMID: 25311193]
[58]
Innocenti F, Undevia S, Chen P, et al. Pharmacogenetic analysis of interindividual irinotecan (CPT-11) pharmacokinetic (PK) variability: Evidence for a functional variant of ABCC2. J Clin Oncol 2010; 22(14): 2010.
[59]
Abdallah EA, Fanelli MF, Souza E Silva V, et al. MRP1 expression in CTCs confers resistance to irinotecan-based chemotherapy in metastatic colorectal cancer. Int J Cancer 2016; 139(4): 890-8.
[http://dx.doi.org/10.1002/ijc.30082] [PMID: 26950035]
[60]
Liang X-J. Nanopharmaceutics: The potential application of nanomaterials. USA: World Scientific 2013.
[61]
Abuchowski A, McCoy JR, Palczuk NC, van Es T, Davis FF. Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J Biol Chem 1977; 252(11): 3582-6.
[PMID: 16907]
[62]
Hoch U, Staschen C-M, Johnson RK, Eldon MA. Nonclinical pharmacokinetics and activity of etirinotecan pegol (NKTR-102), a long-acting topoisomerase 1 inhibitor, in multiple cancer models. Cancer Chemother Pharmacol 2014; 74(6): 1125-37.
[http://dx.doi.org/10.1007/s00280-014-2577-7] [PMID: 25228368]
[63]
Adkins CE, Nounou MI, Hye T, et al. NKTR-102 Efficacy versus irinotecan in a mouse model of brain metastases of breast cancer. BMC Cancer 2015; 15(1): 685.
[http://dx.doi.org/10.1186/s12885-015-1672-4] [PMID: 26463521]
[64]
Sy SK, Sweeney TD, Ji C, Hoch U, Eldon MA. Etirinotecan pegol administration is associated with lower incidences of neutropenia compared to irinotecan administration. Cancer Chemother Pharmacol 2017; 79(1): 57-67.
[http://dx.doi.org/10.1007/s00280-016-3192-6] [PMID: 27904955]
[65]
Jameson GS, Hamm JT, Weiss GJ, et al. A multicenter, phase I, dose-escalation study to assess the safety, tolerability, and pharmacokinetics of etirinotecan pegol in patients with refractory solid tumors. Clin Cancer Res 2013; 19(1): 268-78.
[http://dx.doi.org/10.1158/1078-0432.CCR-12-1201] [PMID: 23136196]
[66]
Awada A, Garcia AA, Chan S, et al. NKTR-102 Study Group. Two schedules of etirinotecan pegol (NKTR-102) in patients with previously treated metastatic breast cancer: a randomised phase 2 study. Lancet Oncol 2013; 14(12): 1216-25.
[http://dx.doi.org/10.1016/S1470-2045(13)70429-7] [PMID: 24095299]
[67]
Vergote IB, Garcia A, Micha J, et al. Randomized multicenter phase II trial comparing two schedules of etirinotecan pegol (NKTR-102) in women with recurrent platinum-resistant/refractory epithelial ovarian cancer. J Clin Oncol 2013; 31(32): 4060-6.
[http://dx.doi.org/10.1200/JCO.2012.45.1278] [PMID: 24081946]
[68]
Rustin G, Vergote I, Micha JP, et al. A multicenter, open-label, expanded phase 2 study to evaluate the safety and efficacy of etirinotecan pegol, a polymer conjugate of irinotecan, in women with recurrent platinum-resistant or refractory ovarian cancer. Gynecol Oncol 2017; 147(2): 276-82.
[http://dx.doi.org/10.1016/j.ygyno.2017.08.026] [PMID: 28935273]
[69]
Nagpal S, Recht CK, Bertrand S, et al. Phase II pilot study of single-agent etirinotecan pegol (NKTR-102) in bevacizumab-resistant high grade glioma. J Neurooncol 2015; 123(2): 277-82.
[http://dx.doi.org/10.1007/s11060-015-1795-0] [PMID: 25935109]
[70]
Aggarwal C, Cohen RB, Yu E, et al. Etirinotecan Pegol (NKTR-102) in third-line treatment of patients with metastatic or recurrent non-small-cell lung cancer: Results of a phase II study. Clin Lung Cancer 2018; 19(2): 157-62.
[http://dx.doi.org/10.1016/j.cllc.2017.10.007] [PMID: 29129435]
[71]
Lenz H-J, Philip P, Saunders M, et al. Randomized study of etirinotecan pegol versus irinotecan as second-line treatment for metastatic colorectal cancer. Cancer Chemother Pharmacol 2017; 80(6): 1161-9.
[http://dx.doi.org/10.1007/s00280-017-3438-y] [PMID: 29043412]
[72]
Perez EA, Awada A, O’Shaughnessy J, et al. Etirinotecan pegol (NKTR-102) versus treatment of physician’s choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): A randomised, open-label, multicentre, phase 3 trial. Lancet Oncol 2015; 16(15): 1556-68.
[http://dx.doi.org/10.1016/S1470-2045(15)00332-0] [PMID: 26482278]
[73]
Twelves C, Cortés J, O’Shaughnessy J, et al. Health-related quality of life in patients with locally recurrent or metastatic breast cancer treated with etirinotecan pegol versus treatment of physician’s choice: Results from the randomised phase III BEACON trial. Eur J Cancer 2017; 76: 205-15.
[http://dx.doi.org/10.1016/j.ejca.2017.02.011] [PMID: 28360015]
[74]
Cortés J, Rugo HS, Awada A, et al. Prolonged survival in patients with breast cancer and a history of brain metastases: Results of a preplanned subgroup analysis from the randomized phase III BEACON trial. Breast Cancer Res Treat 2017; 165(2): 329-41.
[http://dx.doi.org/10.1007/s10549-017-4304-7] [PMID: 28612225]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy