Taxanes and New hormonal agents: How they work?
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1 Taxanes and New hormonal agents: How they work?
2 Taxanes
3
4 Microtubules are highly dynamic cytoskeletal fibres that are composed of tubulin of which are crucial to mitosis and cell division. Jordan Nat Rev Cancer 2004
5 Microtubules functions Cell shape Transport of vesicles Mitochondrial function Cell signalling Cell lldivision i i and mitosis i
6 Emerging mechanistic scenarios of the effects of taxane-based chemotherapy on microtubules and androgen receptor signaling. Mistry S J, and Oh W K Mol Cancer Ther 2013;12:
7 Abiraterone acetate
8 17 hydroxylase lyase Agarwal Fut Oncol 2010 modified
9 enzalutamide
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11 Testosterone & AR: Their role in PC
12 Logothetis Cancer Disc 2013
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15 Seruga Nat Rev Clin Oncol 2011
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18 ES Antonarakis Oral presentation June 1, 2014
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21 S Antonarakis Oral presentation June 1, 2014
22 Azad Poster Highlights sessione May 30, 2014
23 ARv7, which lacks the hinge region, did not co sediment with microtubules, unlike ARv567. Nuclear accumulation and transcriptional activity of ARv7 was unaffected by taxane treatment.
24 chaarted
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26 Sweeney Abs #LBA2 Plenary session June 1, 2014
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30 C. Sweeney Abs #LBA2 Plenary session June 1, 2014
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32 Chemotherapy in hormone sensitive Issues Rationale Selection criteria Side effects PC Magnitude of the results Additional data
33 Sweeney Abs #LBA2 Plenary session June 1, 2014
34 Outline Level Eighth Outline Level Selection criteria? Outline Level Ninth Outline LevelFare clic per modificare stili del testo dello schema Breast cancer Prostate cancer Click to edit the outline text format ER/PGR pos vs neg DRE Clinical/biological Second Outline Level criteria (St.Gallen Third OutlineLevel guidelines) Ki67 HER2 status ER status Fourth Outline Level Fifth Outline Level Sixth Outline Level Seventh Click to edit the outline text format GS PSA Second Outline Level Third OutlineLevel Fourth Outline Level Fifth Outline Level Sixth Outline Level Seventh
35 CHAARTED definition of the risk High ihvolume Visceral mets and/or 4 bone mets (at last 1 beyond pelvis and 4 bone mets (at last 1 beyond pelvis and vertebral column)
36 CHAARTED definition of the risk High ihvolume Visceral mets and/or 4 bone mets (at last 1 beyond pelvis and vertebral column) MJ Morris Discussant Plenary session June 1, 2014
37 Side effects CHAARTED Anemia 1 Thrombocytopenia Neutropenia 12 Febrile neutropenia 6 Fatigue 4
38 Side effects CHAARTED TAX 327 Anemia 1 5 Thrombocytopenia 1 Neutropenia Febrile neutropenia 6 3 Fatigue 4 5
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40 Will chemo became the new standard for hormonosensitive PC pts? t? YES (fora quote of pts waiting moreaccurate selection criteria) Are the presented data enough? NO (additional analyses are needed)
41 Chemo in early stages
42 Neo adjuvant (surgery) down organ confin ed author year Drug GS PSA T # T PSA mfu %RFb mar gin Pettaway 2000 KET+DOX/VBL+E + TAB (duration: 12 wks) >8 > NR NR Clark 2001 VP16+E x 21 d/ 4 w x 3 >8 >15 2B Hussain* 2003 DOC/3w + E 280 TID x 3 6 >8 >15 >2b (#10) Dreicer 2004 DOC w x 6 >8 >15 2b 3 29 NR Beer 2004 DOC+MITOX w x 4 (phase I) > 4+3 >15 2c 3a 21 NR 20/2 1 Konety 2004 Carbo AUC 6 + PCT 180 mg/sqm+ EMP 280 TID + LHRH A x 4 6 Febbo 2005 DOC w x > ( MRI) 76 NR NR >8 > NR NR NR NR
43 Neo adjuvant (XRT) author year Drug GS PSA T # mfu %RFb Ben Josef 2001 VP16+E x 2 XRT + E >7 > (3y DFS) Hussain* 11 XRT 2003 DOC/3w + E 280 TID x 3 6 >8 >15 >2b (2 HT) Zelefsky 2004 VBL+E x 2 XRT + VBL+E x 1 >8 >20 > (5y)
44 Adjuvant Pilepich [RTOG 81 12] (Am J Clin Oncol 1986) XRT ( Gy) CTX+DOX+CDDP Schmidt (Eur Urol1996) XRT or surgery E 600 mg/sqm/d x 2 years CTX 1 g/sqm/3w x 2 years observation
45 CALGB neo Phase III Study of Radical Prostatectomy Alone Versus adj Neoadjuvant Docetaxel in High Risk Localized Prostate t Cancer RTOG 9902 adj Phase III randomized d study of androgen suppression and radiotherapy with or without subsequent paclitaxel, estramustine, and etoposide in patients with localized high-risk prostate cancer Click to edit the outline text format SWOG 9921 adj Adjuvant Androgen Deprivation Versus Mitoxantrone Plus Prednisone Plus Androgen Deprivation in Selected High Risk Prostate Cancer Patients Following Radical Prostatectomy: Phase III Second Outline Level XRP6976J/3501 adj A Multicenter, Open-Label, Randomized, Phase III Trial FRE-FNCLCC- GETUG-12/0203 neo adj Third Outline Level Comparing Immediate Adjuvant Hormonal Therapy (ELIGARD - leuprolide acetate) in Combination with TAXOTERE Administered Every Three Weeks Versus Hormonal Therapy Alone Versus Deferred Therapy Followed by the Same Therapeutic Options in Patients at High Risk of Relapse After Radical Prostatectomy Fourth Outline Level Fifth Outline Level Phase III randomized study of neoadjuvant releasing factor agonist therapy and antiandrogen therapy with or without docetaxel and estramustine in patients with locally ll advanced d prostate t cancer or with a high h risk of relapse
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48 Given the lack of phase III trials, there is limited data regarding the role of (neo) adjuvant chemotherapy with or without ADT prior to RP in localized or locally advanced prostate cancer
49 K Fizazi Oral presentation June 1, 2014
50 K Fizazi Oral presentation June 1, 2014
51 K Fizazi Oral presentation June 1, 2014
52 K Fizazi Oral presentation June 1, 2014
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