1. MEME KANSERİ HORMONOTERAPİDE JİNEKOLOJİK SORUNLAR Prof.Dr.Kunter Yüce Hacettepe Üniversitesi Tıp Fakültesi Kadın Hast ve Doğum Anabilim Dalı Jinekolojik Onkoloji Ünitesi Başkanı
2. 1896 1950 günümüz Beatson Oo forektomi Tamoxifen Additive r e s ept ö r blo kajı Modern AIs Adrenale k tom i Estro j en depriva sy on u Fulvestrant 1896 …… Hipofizektomi Ablasyon DES; Ethinylestradiol E ndo k rin t edavinin gelişmesi
52. Phase III Randomized Study of Tamoxifen and Raloxifene (STAR) for the Prevention of Breast Cancer in Postmenopausal Women
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54. 1. jenerasyon non-steroidal aromataz inhibitörü (reversibl inhibisyon): Aminoglutethimide Eskiden ilk hormon tedavisinde başarısızlık üzerine en çok kullanılan ikincil tedavi Böbrek üstü bezinin işlevini azaltabilir,bu nedenle kortikosteroid replasmanı gerektirebilir. Toksik etkisi çok: uyuşukluk,ateş,döküntü, % 35 ilaç bırakma jinekolojik sorun yok
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56. aromataz inhibitörü Anastrozole Arimidex ® ATAC (Arimidex, Tamoxifen, Alone or in Combination) Jinekolojik yan etkiler ve histerektomiler
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58. Endometrial sub-proto k ol (2 yıl ) 0 0 1 Pol i p (at ipi bilinmeyen ) 1 1 0 At ipik hiperplazi 20 8 5 Pol i p (a tipisiz ) 209 ( % 82) 44 ( % 81) 64 ( % 91) Total – Normal 1 0 0 Diğer 0 0 0 Kompleks hiperplazi 23 0 1 Sekretuar / proliferatif endometrium 45 ( % 18) 9 ( % 17) 6 ( % 9) Total - Anormal Bas al (N=254) Tamoxifen (N=53) Anastrozole (N=70)
60. Yan etkiler * 0.2 0.4 0.6 0.8 1.0 2.0 1.5 Sıcak basması Odds ratio (anastrozole / tamoxifen) Anastrozole iyiliği tamoxifen iyiliği Va j inal kanama Va j inal akıntı Endometrial kanser ** Kırık *** İ s k emi k serebrovasküler olay Ven öz tromboemboli k olay D erin ven öz tromboemboli k olay * Tedavi sırası veya ilaç kesildikten 14 gün sonra yan etkiler ** Önceden h i stere k tom i olmuş hastalar hariç *** Rekürensten herhangibir zaman önce olan kırıklar ( artık tedavi almayanlar dahil) Eklem hastalıkları
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62. Jinekolojik yan etkili olguların özeti Tamoxifen (n=3094)* n (%) Anastrozole (n=3092)* n (%) Tüm İlaç ilgili Ciddi Bırakmaya yol açan 634 (20.5) 386 (12.5) 52 (1.7) 28 (0.9) 1057 (34.2) † 736 (23.8) 199 (6.4) 56 (1.8) * Tedavi gören tüm hastalar † p<0.001 Jinekolojik yan etkiler
63. To plam ji ne k olo j i k yan etkiler Hastalar (%)* * Tedavi gören tüm hastalar p< 0.0001 634 ( % 20.5) 1057 ( % 34.2) Anastrozole (n=3092) Tamoxifen (n=3094)
64. Va j inal kanama Hastalar (%)* 0-2.5 yıl 2.5-5 yıl To plam 135 (6.0%) 90 (4.0%) 27 (1.2%) 61 (2.7%) 115 (5.2%) 186 (8.3%) p <0.0001 * Uterusu duran hastalar . Kanama birden çok olabilir,bunlar değişik zaman kategorilerinde belirtilmişlerdir. Anastrozole (n=2229) Tamoxifen (n=2236)
65. Leukorrhea Hastalar (%)* * Uterusu duran hastalar 0-2.5 y ıl 2.5-5 y ıl To plam Vulvovaginitis: anastrozole ve tamoxifen gruplarında sırasıyla % 10.2 vs % 12.1 218 (9.7%) 61 (2.7%) 28 (1.3%) 14 (0.6%) 196 (8.8%) 46 (2.1%) p <0.0001 Anastrozole (n=2229) Tamoxifen (n=2236)
66. Endometrial h i perpla z i 0-2.5 y ıl 2.5-5 y ıl Hastalar (%)* * Uterusu duran hastalar Total 136 (6.1%) 53 (2.4%) 87 (3.9%) 10 (0.4%) 6 (0.3%) 16 (0.7%) p <0.0001 Anastrozole (n=2229) Tamoxifen (n=2236)
67. Endometrial neopla z i Hastalar (%)* * Uterusu duran hastalar 0-2.5 y ıl 2.5-5 y ıl Total 15 (0.7%) 69 (3.1%) 55 (2.5%) 8 (0.4%) 23 (1.0%) 118 (5.3%) p <0.0001 Anastrozole (n=2229) Tamoxifen (n=2236)
68. Endometrial k ar s inom # Hastalar (%)* # Rekürensten önce herhangibir zaman saptanan yeni kanser * Uterusu duran hastalar 0-2.5 y ıl 2.5-5 y ıl Total p =0.02 2 (0.1%) 3 (0.1%) 5 (0.2%) 10 (0.5%) 16 (0.8%) 4 (0.2%) Anastrozole (n=2229) Tamoxifen (n=2236)
69. Hi stere k tom i insidansı Hastalar (%)* * Uterusu duran hastalar p <0.0001 30 (1.3%) 115 (5.1%) Anastrozole (n=2229) Tamoxifen (n=2236)
70. Hi stere k tom i sebepleri Tamoxifen (n=2236)* n (%) Anastrozole (n=2229)* n (%) Malign Benign Prolaps Fibroid Pol i p Ovarian ki st Diğer 7 (0.3) 23 (1.0) 7 (0.3) 8 (0.4) 1 (<0.1) 2 (0.1) 5 (0.2) 20 (0.9) 95 (4.2) 32 (1.4) 15 (0.7) 14 (0.6) 4 (0.2) 30 (1.3) * Uterusu duran hastalar
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74. ER antagonisti,ER downregülasyon F ulvestrant Faslodex ® 250 mg IM ayda bir kez FDA: hormon-reseptör pozitif,ilk antiöstrojen tedavi ile ilerleme gösteren postmenopozal metastatik meme Ca hastaları
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Notes de l'éditeur
The ATAC (‘Arimidex’, Tamoxifen, Alone or in Combination) trial is a large, double-blind randomised trial comparing 5 years’ anastrozole (‘Arimidex) with tamoxifen alone or in combination with anastrozole, as adjuvant therapy in 9366 postmenopausal women with early breast cancer. Based on the findings of the first analysis, it was decided that combination therapy (anastrozole plus tamoxifen) should be discontinued, because it demonstrated no benefit compared with tamoxifen monotherapy in terms of either efficacy or tolerability. References The ATAC Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet 2002;359:2131-9. The ATAC Trialists' Group. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial efficacy and safety update analyses. Cancer 2003;98:1802-10.
Pre-defined adverse events occurred with a similar frequency to previous reports. The incidence of venous thromboembolic events, ischaemic cerebrovascular events, endometrial cancer, vaginal bleeding, vaginal discharge and hot flushes continued to be lower in women treated with anastrozole compared with tamoxifen. Fractures occurred more frequently in the anastrozole group compared with tamoxifen, although risk ratios remained constant over the treatment period. Joint symptoms were also more common in the anastrozole group.
Symptoms Other – genital oedema, abnormal sexual function Pathologies Endometrial disorder/hyperplasia/neoplasia/carcinoma and Uterine disorder / neoplasia Cervical disorder / neoplasia / cervicitis Ovarian disorder / carcinoma Salpingitis / vulvovaginitis Vaginal / vulval disorder / neoplasia
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