Differences and similarities of epothilones

Current Cancer Therapy Reviews

Volumn 7, Issue 1, 2011, Pages 10-36

  Krause, Werner ^a   Klar, Ulrich ^a  

^a BAYER PHARMA AG   (Germany)

Author keywords

Clinical development; Cytotoxic drugs; Epothilones; Microtubular inhibitors; Multidrug resistance; Oncology

Indexed keywords

21 AMINOEPOTHILONE B; 9,10 DIDEHYDROEPOTHILONE D; DOCETAXEL; EPOTHILONE B; EPOTHILONE D; IXABEPILONE; PACLITAXEL; SAGOPILONE; TAXANE DERIVATIVE;

ALLERGIC REACTION; ANEMIA; ARTHRALGIA; ARTICLE; ASTHENIA; BREAST CANCER; COLON CANCER; CONSTIPATION; CONTINUOUS INFUSION; DIARRHEA; DRUG SAFETY; DRUG TOLERABILITY; FATIGUE; FEBRILE NEUTROPENIA; GASTROINTESTINAL DISEASE; GLIOBLASTOMA; HEMATOLOGIC DISEASE; HEPATOBILIARY SYSTEM CANCER; HUMAN; HYPOKALEMIA; KIDNEY CANCER; LUNG NON SMALL CELL CANCER; LYMPHOCYTOPENIA; LYMPHOMA; MELANOMA; MULTIDRUG RESISTANCE; MYALGIA; NAUSEA; NEUROPATHY; NEUTROPENIA; NONHUMAN; OVARY CANCER; PANCREAS CANCER; PHASE 2 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PRIORITY JOURNAL; PROSTATE CANCER; SARCOMA; SENSORY NEUROPATHY; SIDE EFFECT; STOMACH CANCER; STOMATITIS; STRUCTURE ACTIVITY RELATION; SUDDEN DEATH; THROMBOCYTOPENIA; VOMITING;

EID: 79551638867     PISSN: 15733947     EISSN: None     Source Type: Journal    
DOI: 10.2174/157339411794474155     Document Type: Article

References (131)

1. Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT. Plant antitumoragents. VI. The isolation and structure of Taxol, a novel antileukemicand antitumor agent from Taxus brevifolia. J Am Chem Soc 1971; 93: 2325-7.
2. Fuchs DA, Johnson RK. Cytologic evidence that taxol, an antineoplasticagent from Taxus brevifolia, acts as a mitotic spindle poison. Cancer Treat Rep 1978; 62: 1219-22.
3. Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly invitro by Taxol. Nature 1979; 277: 665-7.
4. Bollag DM, McQueney PA, Zhu J, et al. Epothilones, a new class ofmicrotubule-stabilizing agents with a taxol-like mechanism of action. Cancer Res 1995; 55: 2325-33.
5. Giannakakou P, Gussio R, Nogales E, et al. A common pharmacophorefor epothilone and taxanes: molecular basis for drug resistanceconferred by tubulin mutations in human cancer cells. Proc Natl Acad Sci USA 2000; 97: 2904-9.
6. Kowalski RJ, Giannakakou P, Hamel E. Activities of the microtubulestabilizingagents epothilones A and B with purified tubulin and incells resistant to paclitaxel (Taxol(R)). J Biol Chem 1997; 272 (4): 2534-2541.
7. Bode CJ, Gupta ML Jr, Reiff EA, Suprenant KA, Georg GI, Himes RH. Epothilone and paclitaxel: unexpected differences in promotingthe assembly and stabilization of yeast microtubules, Biochemistry 2002; 41: 3870-3874.
8. Horwitz SB, Lothstein L, Manfredi JJ, et al. Taxol: mechanisms ofaction and resistance. Ann N Y Acad Sci 1986; 466: 733-44.
9. Melton L. Cellular pump changes prospect of disease resistance. Lancet 2001; 357: 1186.
10. Kavallaris M, Kuo DY, Burkhart CA, et al. Taxol-resistant epithelialovarian tumors are associated with altered expression of specific β-tubulin isotypes. J Clin Invest 1997; 100: 1282-93.
11. Lu Q, Luduena RF. Removal of β-III isotype enhances taxol inducedmicrotubule assembly. Cell Struct Funct 1993; 18: 173-182.
12. Sève P, Mackey J, Isaac S, et al. Class III β-tubulin expression intumor cells predicts response and outcome of patients with non-smallcell lung cancer receiving paclitaxel. Mol Cancer Ther 2005; 4: 2001-7.
13. Mozzetti S, Ferlini C, Concolino P, et al. Class III β-tubulin overexpressionis a prominent mechanism of paclitaxel resistance in ovariancancer patients. Clin Cancer Res 2005; 11: 298-305.
14. Jordan MA, Miller H, Ray A, et al. The Pat-21 breast cancer modelderived from a patient with primary Taxol resistance recapitulates thephenotype of its origin has altered β-tubulin expression and is sensitiveto ixabepilone. Presented at the 97th AACR Annual Meeting, April 1-5, 2006, Washington, District of Columbia, Late breakingposter session, Abstract LB-280.
15. Dumontet C, Jordan MA, Lee FFY. Ixabepilone: targeting βIIItubulinexpression in taxane-resistant malignancies. Mol Cancer Ther 2009; 8: 17-25.
16. Nicolaou K, Ritzen A, Namato K. Recent developments in the chemistry, biology, and medicine of the epthilones. Chem Commun(Camb) 2001; 17: 1523-1535.
17. Kolman A. Activity of epothilones. Curr Opin Investig Drugs 2005; 6: 616-622.
18. de Jonge M, Verweij J. The Epothilone Dilemma. J Clin Oncol 2005; 23: 9048-905.
19. Harrison M, Swanton C. Epothilones and new analogues of the microtubulemodulators in taxane-resistant disease. Expert Opin Investig Drugs 2008; 17: 523-546.
20. Sudo T, Nitta M, Saya H, Ueno NT. Dependence of paclitaxel sensitivityon a functional spindle assembly checkpoint. Cancer Res 2004; 64: 2502-8.
21. Cahill DP, Lengauer C, Yu J, et al. Mutations of mitotic checkpointgenes in human cancers. Nature 1998; 392: 300-3.
22. Fumoleau P, Coudert B, Isambert N, Ferrant E. Novel tubulintargetingagents: anticancer activity and pharmacologic profile ofepothilones and related analogues. Ann Oncol 2007; 18: v9-15.
23. Hoffmann J, Vitale I, Buchmann B, et al. Improved cellularpharmacokinetics and pharmacodynamics underlie the wide anticanceractivity of sagopilone. Cancer Res 2008; 68: 5301-8.
24. Alexander E. Sagopilone. Drugs Future 2008; 33: 496-505.
25. Trivedi M, Budihardjo I, Loureiro K, Reid TR, Ma JD. Epothilones: a novel class of microtubule-stabilizing drugs forthe treatment of cancer. Future Oncol 2008; 4: 483-500.
26. Klar U, Hoffmann J, Giurescu M. Sagopilone (ZK-EPO): from anatural product to a fully synthetic clinical development candidate. Expert Opin Investig Drugs 2008; 17: 1735-48.
27. Chou TC, Dong H, Zhang X, Tong WP, Danishefsky SJ. Therapeutic Cure against Human Tumor Xenografts in Nude Mice bya Microtubule Stabilization Agent, Fludelone, via Parenteral or Oral Route. Cancer Res 2005; 65: 9445-54.
28. Lee FYF, Borzilleri R, Fairchild CR, et al. Preclinical discoveryof ixabepilone, a highly active antineoplastic agent Cancer Chemother Pharmacol 2008; 63: 157-166.
29. Wang H, Wang Z, Wang S, et al. Preclinical pharmacology ofepothilone D, a novel tubulin-stabilizing antitumor agent. Cancer Chemother Pharmacol 2005; 56: 255-260.
30. Mok TSK, Choi E, Yau D, et al. Effects of Patupilone(Epothilone B; EPO906), a Novel Chemotherapeutic Agent, in Hepatocellular Carcinoma: An in vitro Study. Oncology 2006; 71: 292-296.
31. O'Reilly T, Wartmann M, Brueggen J, et al. Pharmacokineticpro Wle of the microtubule stabilizer patupilone in tumor-bearingrodents and comparison of anti-cancer activity with other MTS invitro and in vivo. Cancer Chemother Pharmacol 2008; 62: 1045-1054.
32. Mani S, McDaid H, Hamilton A, et al. Phase I clinical andpharmacokinetic study of BMS-247550, a novel derivative ofepothilone B, in solid tumors. Clin Cancer Res 2004; 10: 1289-98.
33. Gadgeel SM, Wozniak A, Boinpally RR, et al. Phase I clinicaltrial of BMS-247550, a derivative of epothilone B, using acceleratedtitration 2B design. Clin Cancer Res 2005; 11: 6233-6239.
34. Aghajanian C, Burris HA 3rd, Jones S, et al. Phase I study of thenovel epothilone analog ixabepilone (BMS-2t47550) in patientswith advanced solid tumors and lymphomas. J Clin Oncol 2007; 25: 1082-8.
35. Takimoto C H, Fu S, Dhillon N, et al. Evaluation ofpharmacokinetics (PK) and pharmacodynamics (PD) ofpatupilone and warfarin in patients (pts) with advanced solidtumors: An open-label, phase I study. J Clin Onc 2008 ASCOAnnual Meeting Proceedings (Post-Meeting Edition). Vol. 26, No 15S (May 20 Supplement), 2008: 2548.
36. Shimizu T, Yamamoto N, Yamada Y, et al. Phase I clinical andpharmacokinetic study of 3-weekly, 3-h infusion of ixabepilone(BMS-247550), an epothilone B analog, in Japanese patientswith refractory solid tumors. Cancer Chemother Pharmacol 2008; 61: 751-8.
37. Burris HA, Awada A, Jones S, et al. Phase I study of the novelepothilone BMS-247550 administered weekly in patients (pts)with advanced malignancies. J Clin Oncol (Meeting Abstracts) 2002; 21: 412
38. Dickson N, Peck R, Wu C, Burris H. Ixabepilone given weeklyin patients with advanced malignancies: final efficacy and safetyresults of a Phase I trial. J Clin Oncol (Meeting Abstracts) 2006; 24 (18 Suppl): 2040.
39. Awada A, Piccart MJ, Jones SF, et al. Phase I dose escalationstudy of weekly ixabepilone, an epothilone analog, in patientswith advanced solid tumors who have failed standard therapy. Cancer Chemother Pharmacol 2009; 63: 417-425.
40. Zhuang SH, Agrawal M, Edgerly M, et al. A Phase I clinical trialof ixabepilone (BMS-247550), an epothilone B analog, administered intravenously on a daily schedule for 3 days. Cancer 2005; 103: 1932-8.
41. Abraham J, Agrawal M, Bakke S, et al. Phase I trial and pharmacokineticstudy of BMS-247550, an epothilone B analog, administeredintravenously on a daily schedule for five days. J Clin Oncol 2003; 21: 1866-73.
42. Widemann BC, Fox E, Goodspeed WJ, et al. Phase I trial of theepothilone B analog BMS-247550 (ixabepilone) in children with refractorysolid tumors [abstract]. 41st ASCO Annual Meeting; 2005May; Orlando, FL, USA.
43. Widemann B, Goodspeed W, Goodwin A, Fojo T, Bulis F, Fox E. Phase I trial and pharmacokinetic study of ixabepilone administereddaily for 5 days in children and adolescents with refractory solid tumors. J Clin Oncol 2009; 27: 550-6.
44. Calvert PM, O'Neill V, Twelves C, et al. A Phase I Clinical and Pharmacokinetic Study of EPO906 (Epothilone B), Given Every Three Weeks, in Patients with Advanced Solid Tumors. Proc Am Soc Clin Oncol 2001; 20: (Abstract 429).
45. Smit WM. Phase I/II dose-escalation trial of patupilone every 3weeks in patients with resistant/refractory ovarian cancer. Eur J Cancer 2005; 3 (2): 261.
46. Sánchez JM, Mellemgaard A, Perry M, et al. Efficacy and safety ofpatupilone in non-small cell lung cancer (NSCLC): a phase I/II trial [abstract 7104]. 42nd ASCO Annual Meeting; 2006 June; Atlanta, GA, USA.
47. Melichar B, Casado E, Taberno J, et al. Patupilone in chemotherapypretreatedpatients with advanced colorectal cancer (CRC) receivingnutritional support and intensive diarrhea management: a phase I multicentertrial [abstract 8198]. ESMO, Istanbul; 2006.
48. Osterlind K, Sanchez JM, Zatloukal P, et al. Phase I/II dose escalationtrial of patupilone every 3 weeks in patients with non-small celllung cancer. ASCO Meeting Abstracts 23: 7110 (2005).
49. Reid T, Takimoto C, Verschragen C, et al. Evaluation of safety, tolerability, and pharmacokinetics (PK) of patupilone in patients (pts)with advanced solid tumors and varying degree of hepatic function:an open-label Phase I study. Poster ASCO 2008.
50. Rubin EH, Rothermel J, Tesfaye F, et al. Phase I dose-finding studyof weekly single-agent patupilone in patients with advanced solid tumors. J Clin Oncol 2005; 23: 9120-9.
51. Schmid P, Kiewe P, Kühnhardt D, et al. A phase I study of the novelthird-generation epothilone ZK-EPO in patients with advanced solidtumors. Poster at the ASCO Meeting, May 14-17, 2005, Orlando, FL, USA.
52. Arnold D, Voigt W, Kiewe P, et al. Weekly administration of sagopilone(ZK-EPO), a fully synthetic epothilone, in patients with refractorysolid tumors: Results of a phase I trial. Br J Cancer 2009; 101 (8): 1241-7.
53. Mekhail T, Chung C, Holden S, et al. Phase I trial of novel epothiloneB analog BMS-310705 IV q 21 days Proc Am Soc Clin Oncol 2003; 22: 129 (Abstract 515).
54. Sessa C, Perotti A, Lladò A, et al. Phase I clinical study of the novelepothilone B analogue BMS-310705 given on a weekly schedule. Ann Oncol 2007; 8 (9): 548-53.
55. Piro LD, Rosen LS, Parson M, et al. KOS-862 (epothilone D): Acomparison of two schedules in patients with advanced malignancies. Proc Am Soc Clin Oncol 2003; 22: 135 (Abstract 539).
56. Stopeck A, Moulder S, Jones S, et al. Phase I trial of KOS-1584 (anovel epothilone) using two weekly dosing schedules. ASCO Meeting Abstracts 2007 25: 2571.
57. Villalona-Calero M, Goel S, Schaaf L, et al. First-in-human phase Itrial of a novel epothilone, KOS-1584 [abstract 2003]. J Clin Oncol 2006; 24.
58. Beumer JH, Garner RC, Cohen MB, et al. Human mass balance studyof the novel anticancer agent ixabepilone using accelerator massspectrometry. Invest New Drugs 2007; 25: 327-34.
59. Goel S, Goldberg G, Iacono LC, et al. Effect of ketoconazole on thepharmacokinetics and pharmacodynamics of ixabepilone. J Clin Oncol(Meeting Abstracts) 2006; 24 (18 Suppl): 2005.
60. Goel S, Cohen M, Cömezoglu SN, et al. The effect of ketoconazoleon the pharmacokinetics and pharmacodynamics of ixabepilone: afirst in class epothilone B analogue in late-phase clinical development. Clin Cancer Res 2008; 14: 2701-9.
61. Plummer R, Woll P, Fyfe D, et al. Phase i and pharmacokinetic studyof ixabepilone in combination with carboplatin in patients with advancedsolid malignancies. Clin Cancer Res 2008; 14: 8288-94.
62. Takimoto CH, Liu PY, Lenz H, et al. Southwest oncology groupearly therapeutics committee l. A phase I pharmacokinetic (PK) studyof the epothilone B analogue, ixabepilone (BMS-247550) in patients(pts) with advanced malignancies and varying degrees of hepatic impairment. A SWOG early therapeutics committee and NCI organ dysfunctionworking group trial. J Clin Oncol (Meeting Abstracts) 2006; 24: 2004.
63. Forster M, Kaye S, Oza A, et al. A phase Ib and pharmacokinetictrial of patupilone combined with carboplatin in patients with advancedcancer. Clin Cancer Res 2007; 13: 4178-84.
64. Stupp R, Tosoni A, Taal W, et al. on behalf of the EORTC Brain Tumor Group. Phase II trial of the epothilone analog sagopilone(ZK 219477; ZK EPO) in patients with recurrent glioblastoma:Initial report of the EORTC study 2606. ASCO Meeting Abstracts May 20 2008: 201.
65. Holen KD, Syed S, Hannah AL, et al. Phase I study using continuousintravenous (CI) KOS-862 (Epothilone D) in patientswith solid tumors. J Clin Oncol 2004; 22 (14 suppl): 133 (Abstract 2024).
66. Baselga J, Zambetti M, Llombart-Cussac A, et al. Phase II genomicsstudy of ixabepilone as neoadjuvant treatment for breastcancer. J Clin Oncol 2009; 27: 526-34.
67. Perez EA, Lerzo G, Pivot X, et al. Efficacy and safety of ixabepilone(BMS-247550) in a phase II study of patients with advancedbreast cancer resistant to an anthracycline, a taxane, andcapecitabine. J Clin Oncol 2007; 25: 3407-14.
68. Roché H, Yelle L, Cognetti F, et al. Phase II clinical trial ofixabepilone (BMS-247550), an epothilone B analog, as first-linetherapy in patients with metastatic breast cancer previouslytreated with anthracycline chemotherapy. J Clin Oncol 2007; 25: 3415-20.
69. Thomas E, Tabernero J, Fornier M, et al. Phase II clinical trial of Ixabepilone (BMS-247550), an epothilone B analog, in patientswith taxane resistant metastatic breast cancer. J Clin Oncol 2007; 23: 3399-406.
70. Denduluri N, Low JA, Lee JJ, et al. Phase II trial of ixabepilone, an epothilone B analog, in patients with metastatic breast cancerpreviously untreated with taxanes. J Clin Oncol 2007; 25: 3421-7.
71. Low JA, Wedam SB, Lee JJ, et al. Phase II clinical trial of ixabepilone(BMS-247550), an epothilone B analog, in metastaticand locally advanced breast cancer. J Clin Oncol 2005; 23: 2726-34.
72. Denduluri N, Lee JJ, Walshe J, et al. Phase II trial of ixabepilone, an epothilone B analog, given daily for three days every threeweeks, in metastatic breast cancer. Invest New Drugs 2007; 25: 63-7.
73. Hussain M, Tangen CM, Lara PN Jr, et al. Southwest Oncology Group. Ixabepilone (epothilone B analogue BMS-247550) is activein chemotherapy-naive patients with hormone-refractoryprostate cancer: a Southwest Oncology Group trial S0111. J Clin Oncol 2005; 23: 8724-9.
74. Galsky MD, Small EJ, Oh WK, et al. Multi-institutional randomizedphase II trial of the epothilone B analog ixabepilone (BMS-247550) with or without estramustine phosphate in patients withprogressive castrate metastatic prostate cancer. J Clin Oncol 2005; 23: 1439-46.
75. Liu G, Wang W, Dipaola R, Carducci M, Wilding G. A phase IIstudy of a weekly schedule of BMS-247550 for patients withhormone-refractory prostate cancer: A trial of the Eastern Cooperative Oncology Group (E3803) [abstract 4618]. 42nd ASCOAnnual Meeting; Atlanta, GA, USA, June 2006.
76. Rosenberg JE, Weinberg VK, Kelly WK, et al. Activity of second-line chemotherapy in docetaxel-refractory hormonerefractoryprostate cancer patients: randomized phase 2 study ofixabepilone or mitoxantrone and prednisone. Cancer 2007; 110: 556-63.
77. Rosenberg JE, Galsky MD, Rohs NC, et al. A retrospectiveevaluation of second-line chemotherapy response in hormonerefractoryprostate carcinoma: second line taxane-based therapyafter first-line epothilone-B analog ixabepilone (BMS-247550)therapy. Cancer 2006; 106: 58-62.
78. Posadas EM, Undevia S, Manchen E, et al. A phase II Study of Ixabepilone (BMS-247550) in Metastatic Renal-Cell Carcinoma. Cancer Biol Ther 2007; 6: 490-3.
79. Fojo AT, Menefee ME, Poruchynsky M, et al. A translationalstudy of ixabepilone (BMS-247550) in renal cell cancer (RCC):Assessment of its activity and demonstration of target engagementin tumor cells. Annual Meeting Proceedings. J Clin Oncol 2005 ASCO. 23 (16S): (June 1 Supplement), 2005: 4541.
80. Zhuang SH, Menefee M, Kotz H, et al. A Phase II clinical trial of BMS-247550 (Ixabepilone), a microtubule-stabilizing agent inrenal cell cancer [abstract 4550]. 40th ASCO Annual Meeting;New Orleans, LA, USA, 2004 June.
81. Dreicer R, Li S, Manola J, Haas NB, Roth BJ, Wilding G. Eastern Cooperative Oncology Group. Phase 2 trial of epothilone B analogBMS-247550 (ixabepilone) in advanced carcinoma of the urothelium(E3800): a trial of the eastern cooperative oncology group. Cancer 2007; 1104: 759-63.
82. Vansteenkiste J, Lara PN Jr, et al. Phase II clinical trial of theepothilone B analog, ixabepilone, in patients with non small-cell lungcancer whose tumors have failed first-line platinum-based chemotherapy. J Clin Oncol 2007; 25: 3448-55.
83. Whitehead RP, McCoy S, Rivkin SE, et al. A Phase II trial ofepothilone B analogue BMS-247550 (NSC #710428) ixabepilone, inpatients with advanced pancreas cancer: A Southwest Oncology Group study. Invest New Drugs 2007; 24: 515-20.
84. Eng C, Kindler HL, Nattam S, et al. A phase II trial of the epothiloneB analog, BMS-247550, in patients with previously treated advancedcolorectal cancer. Ann Oncol 2004; 15: 928-32.
85. Ajani JA, Safran H, Bokemeyer C, et al. A multi-center phase IIstudy of BMS-247550 (Ixabepilone) by two schedules in patientswith metastatic gastric adenocarcinoma previously treated with a taxane. Invest New Drugs 2006; 24: 441-446.
86. Singh DA, Taber D, Ansari R, et al. A phase II trial of the epothiloneB analog BMS-247550 in patients (pts) with hepatobiliary cancer(HBC): an updated analysis [abstract 14050]. 42nd ASCO Annual Meeting; Atlanta, GA, USA, 2006 June.
87. Feldman DR, Kondagunta GV, Ginsberg MS, et al. Phase II trial ofixabepilone in patients with cisplatin-refractory germ cell tumors. Invest New Drugs 2007; 25: 487-90.
88. Burtness B, Goldwasser MA, Axelrod R, Argiris A, Forastiere AA. Arandomized phase II study of BMS-247550 (Ixabepilone) given daily × 5 days every 3 weeks or weekly in patients with metastatic or recurrentsquamous cell cancer of the head and neck [abstract 5532]. 42nd ASCO Annual Meeting; Atlanta, GA, USA, 2006 June.
89. O'Connor O, Straus D, Moskowitz C, et al. Targeting the microtubuleapparatus in indolent and mantle cell lymphoma with the novelepothilone anlog BMS 247550 induces major and durable remissionsin very drug resistant disease [abstract 6569]. 41st ASCO Annual Meeting; Orlando, FL, USA, May 2005.
90. Smith SM, Pro B, van Besien K, et al. A Phase II study of epothiloneB analog BMS-247550 (NSC 710428) in patients with relapsed aggressivenon-hodgkin's lymphomas [abstract 6625]. 41st ASCO Annual Meeting; Orlando, FL, USA, 2005 May.
91. Okuno S, Maples WJ, Mahoney MR, et al. Evaluation of epothiloneB analog in advanced soft tissue sarcoma: a phase II study of thephase II consortium. J Clin Oncol 2005; 23: 3069-73.
92. Pavlick AC, Millward M, Farrell K, et al. A phase II study ofepothilone B analog (EpoB)-BMS 247550 (NSC#710428) in stage IVmalignant melanoma (MM) [abstract 7542]. 40th ASCO Annual Meeting; New Orleans, LA, USA, 2004 June.
93. Hussain A, Dipaola RS, Baron AD, et al. A phase IIa trial of weeklyEPO906 in patients with hormone-refractory prostate cancer (HPRC) [abstract 4563]. ASCO Annual Meeting Proceedings; 2004.
94. Chi KN, Beardsley EK, Venner PM, et al. A phase II study of patupilonein patients with metastatic hormone refractory prostate cancer(HRPC) who have progressed after docetaxel. Journal of Clinical Oncology, 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol. 26, No. 15S (May 20 Supplement), 2008: 5166.
95. Poplin E. Safety and efficacy of EPO906 in patients with advancedcolorectal cancer: A review of 2 phase II trials [abstract 1135]. 39thASCO Annual Meeting; 2003 May-June; Chicago, IL, USA.
96. rd ESMO Congress, Stockholm, Sweden, September 12-16, 2008.
97. Abrey LE, Wen P, Govindan R, et al. Patupilone for the treatment ofrecurrent/progressive brain metastases in patients (pts) with non-smallcell lung cancer (NSCLC): An open-label phase II study. J Clin Oncol 2008; 26: 2033.
98. Conlin AK, D'Andrea G, Hudis CA, et al. Phase II trial of patupilonein patients (pts) with breast cancer brain metastases (BCBM) progressingor recurring after whole brain radiation therapy (WBXRT). ASCO Meeting Abstracts May 20 2008: 1086.
99. Venook AP, Poon R, Kang YK, et al. Evaluation of patupilone asmonotherapy in patients with advanced hepatocellular carcinoma(HCC) [abstract 15055]. 43rd ASCO Annual Meeting; 2007 June;Chicago, IL, USA.
100. Thompson JA. Phase II trial evaluating the safety and efficacy of EPO906 in patients with advanced renal cancer [abstract 1628]. Proc Am Soc Clin Oncol 2003.
101. Hsin KW, Boyer M, Ducreux M, et al. Efficacy of patupilone inadvanced local or metastatic gastric cancer: a phase IIa trial [abstract4069]. 42nd ASCO Annual Meeting; 2006 June; Atlanta, GA, USA
102. Anthony LB. An open-label phase IIA trial evaluating the safetyand efficacy of EPO906 as therapy in patients with metastaticcarcinoid and other neuroendocrine tumors [abstract 1413]. Proc Am Soc Clin Oncol 2003.
103. Rustin GJ, Reed NS, Jayson G, et al. Phase II trial of the novelepothilone ZK-EPO in patients with platinum resistant ovariancancer [abstract]. J Clin Oncol 2007; 25: 280s.
104. rd ESMO Congress, September 12-16, 2008, Stockholm, Sweden.
105. th ECCO Congress, September 23-27, 2007, Barcelona, Spain.
106. Graff J, Smith DC, Neerukonda L, et al. Prostate Cancer Clinical Trials Consortium. Phase II study of sagopilone (ZK-EPO) plusprednisone as first-line chemotherapy in patients with metastaticandrogen-independent prostate cancer (AIPC). ASCO Meeting Abstracts May 20 2008: 5141.
107. Wenk D, DeConti RC, Urbas P, et al. Phase II trial of sagopilone(ZK-EPO), a novel epothilone, in patients with metastatic melanoma. ASCO Meeting Abstracts May 20 2008: 9046.
108. Silvani A, Fiumani A, Scaioli V, et al. A phase II study evaluatingsystemic sagopilone (ZK-EPO) treatment in patients with recurrentmalignant gliomas. ASCO Meeting Abstracts May 20 2008: 2083.
109. Overmoyer B, Waintraub S, Kaufman PA, et al. Phase II trial of KOS-862 (epothilone D) in anthracycline and taxane pretreatedmetastatic breast cancer. ASCO Meeting Abstracts Jun 1 2005: 778
110. Beer TM, Higano CS, Saleh M, et al. Phase II study of KOS-862in patients with metastatic androgen independent prostate cancerpreviously treated with docetaxel. Invest New Drugs 2007; 25: 565-70.
111. Yee L, Lynch T, Villalona-Calero M, et al. A phase II study of KOS-862 (epothilone D) as second-line therapy in non-small celllung cancer [abstract 7127]. 41st ASCO Annual Meeting; 2005May; Orlando, FL, USA; 23 (16S).
112. Jacobs S, Fox B, Krailo MD, et al. Phase II trial of ixabepilone(BMS-247550) in children and young adults with refractory solidtumors: A report from the Children's Oncology Group. J Clin Onc 2008 ASCO Annual Meeting Proceedings (Post-Meeting Edition). Vol 26, No 15S (May 20 Supplement), 2008: 10026.
113. Beer T, Smith DC, Hussain A, et al. Phase II study of first-linesagopilone combined with prednisone in patients with metastaticcastration-resistant prostate cancer. Poster at ASCO Meeting, May 29-June2, 2009, Orlando, FL.
114. Cortes J, Climent MA, Gomez P, et al. A phase I trial of weeklycombination of KOS-862 (epothilone D) and trastuzumab in HER-2 overexpressing malignancies. J Clin Oncol, 2006, ASCOProceedings 2006; 24: 2028.
115. Marshall JL, Ramalingam S, Hwang JJ, et al. Phase I and pharmacokinetic(PK) study of weekly KOS-862 (epothilone D) combinedwith gemcitabine (GEM) in patients with advanced solid tumors. JClin Oncol, 2005, ASCO Proceedings 2005; 23: 2041.
116. Monk JP, Calero-Villanlona M, Dupont J, et al. Phase I trial of KOS-862 (epothilone D) in combination with carboplatin (C) in patientswith solid tumors. J Clin Oncol, 2005, ASCO Proceedings 2005; 23: 2049.
117. Rosen PJ, Rosen L, Britten C et al. KOS-862 (epothilone D): Resultsof a phase I dose-escalating trial in patients with advanced malignancies. Proc Am Soc Clin Oncol 2002; 21: 104a (abstract 413).
118. Schiller JH, Storer B, Tutsch K, et al. Phase I Trial of 3-Hour Infusionof Paclitaxel With or Without Granulocyte Colony-Stimulating Factor in Patients With Advanced Cancer. J Clin Oncol 1994; 12: 241-248.
119. Mitchell PLR, Basser R, Chipman M, et al. A phase I dose-escalationstudy of docetaxel with granulocyte colony-stimulating factor supportin patients with solid tumours. Ann Oncol 2003; 14: 788-794.
120. Tannock IF, de Wit R, Berry WR, et al. for the TAX 327 Investigators. Doacetxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer. N Engl J Med 2004; 351: 1502-12.
121. Fossella FV, DeVore R, Kerr RN, et al. Randomized Phase III trial ofdocetaxel versus vinorelbine or ifosfamide in patients with advancednon-small cell lung cancer previously treated with platinumcontainingregimens. The TAX-320 Non-Small Cell Lung Cancer Study Group. J Clin Oncol 2000; 18: 2354-62.
122. Lin N, Brakora K, Michael Seiden M. BMS-247550 Bristol-Myers Squibb/GBF. Current Opinion in Investigational Drugs 2003: 4: 746-756.
123. Hoffmann J, Fichtner I, Lemm M, et al. Sagopilone crosses theblood-brain barrier in vivo to inhibit brain tumor growth and metastases. Neuro Oncol 2009; 11: 158-166.
124. Gauler TC, Christoph D, Gamarra F, et al. Phase I study of sagopilone(ZK-EPO) in combination with cisplatin in patients with chemotherapy-naïve extensive-disease small-cell lung cancer. Poster atESGO 2009, Stockholm, Sweden.
125. Morrow PK, Divers S, Provencher L, et al. Phase II study of sagopilone(ZK-EPO), a novel epothilone, in patients with recurrent metastaticbreast cancer. Poster at ASCO Meeting, May 29-June2, 2009, Orlando, FL.
126. Campone M, Tomova A, Dittrich C, et al. Phase II trial of the novelepothilone sagopilone (ZK-EPO) in patients with progressive metastaticbreast cancer (MBC). San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, TX.
127. Beardsley EK, Saad F, Eigl B, et al. A Phase II study of patupilone inpatients with metastatic castration-resistant prostate cancer who haveprogressed after docetaxel. Poster at ASCO Meeting, May 29-June2, 2009, Orlando, FL.
128. Smit WM, Sufliarsky J, Werner TL, et al. A Phase II study evaluatingthe safety and efficacy of patupilone in patients with platinum refractory/resistant ovarian, primary fallopian or peritoneal cancer. Posterat ASCO Meeting, May 29-June 2, 2009, Orlando, FL.
129. Ten Bokkel Huinink WW, Sufliarsky J, Smit WM, et al. Safety andefficacy of patupilone in patients with advanced ovarian, primary fallopian, or primary peritoneal cancer: A Phase I, open-label, doseescalationstudy. J Clin Oncol 27, epub, 2009.
130. Sabbatini P, Spriggs DR. Epothilones: Better or more of the same? JClin Oncol 2009; 27 (19): 3079-81.
131. Dizon DS, Blessing JA, McMeekin S, Sharma SK, Di Silvestro P, Alavarez RD. Phase II trial of ixabepilone as second-line treatment inadvanced endometrial cancer: gynecologic oncology Group Trial 129-P. J Clin Oncol J Clin Oncol 2009; 27 (19): 3104-8.