PowerPoint-presentatie · 25/01/2019 1 Hormonale Therapie Alain Bols 19/01/2019 Dr Alain Bols...
20
25/01/2019 1 Hormonale Therapie Alain Bols 19/01/2019 Dr Alain Bols Verpleegkundig congres oncologie De Valkaart Oostkamp 1 19/01/2019 Dr Alain Bols Verpleegkundig congres oncologie De Valkaart Oostkamp 2 3000 BC: Eight cases of tumors or ulcers were described in ancient Egyptian text on trauma surgery. Tumors were treated by cauterization with a “fire drill.” 400 BC: Hippocrates proposed the Humoral Theory of Medicine and attributed cancer to an excess of black bile. He believed the cancer should be left alone, because those who got treatment did not live as long as those who were untreated. 168 BC: Galen, a Roman physician, believed advanced tumors should be operated on by cutting around the affected area. 1846 AD: Anesthesia becomes available and surgery becomes more prominent. Late 1800’s: Surgeons perfected procedures to remove parts of affected tissues, such as mastectomies (removal of the entire breast and lymphatic system of the breast) to prevent outward invasion. 1870-1890: Thomas Beatson discovered that estrogen stimulates breast cancer, providing a foundation for hormone therapy. 1893: Coley’s Toxins were administered as a vaccine to cancer patients. The idea that the immune system could be used to help fight cancer was pioneered. 1890’s: 1895: Wilhelm Rontgen discovered x-rays, which helped in the detection of tumors. 1899: The first successful treatment of cancer with radiation from x-rays. Radiation therapy begins. 1930’s-1940’s: 1939: Charles Huggins discovered that hormones were important for the growth of certain cancers, further paving the way for hormone therapies. 1941: Diethylstilbestrol, a synthetic estrogen, was found to be effective in treating prostate cancer. 1946: The first chemotherapy was discovered by Louis Goodman. Nitrogen mustards, used in WWII chemical warfare, were found to be useful as chemotherapeutic agents against cancer. 1970’s: Less extensive surgery was shown to be equally as effective. Also, 3D radiation delivery was developed with CT, allowing for more accurate radiation dosing. Scientists identified a mutation in the Philadelphia chromosome as the genetic cause of chronic myelogenous leukemia (CML). 1976: The first oncogene was discovered by Harold E. Varmus and J. Michael Bishop. 1980’s: Biological therapy and immunotherapy expanded, as interferon was found to be able to treat cancer. 1995: DNA microarrays were developed to measure gene expression. This led to the possibility of targeted therapy, or targeting genes and processes directly involved in cancer initiation and metastases. Late 1990’s to early 2000’s: Monoclonal antibodies against tumor antigens were approved by the FDA to treat certain cancers. 2001: The first targeted anti- cancer therapy, against CML, was approved. 2010: Sipuleucel-T (a cancer vaccine that boosts the immune system) was approved to treat prostate cancer. A Timeline of Pioneering Cancer Treatments 3000 BC 400 BC 168 BC 1846 AD Late 1800s 1870-1890 1893 1895-1899 1930-1940 1946 1970’s 1976 1980’s 1995 1997-2006 2010
Transcript of PowerPoint-presentatie · 25/01/2019 1 Hormonale Therapie Alain Bols 19/01/2019 Dr Alain Bols...
25/01/2019
1
Hormonale Therapie
Alain Bols
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp1
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp2
3000 BC:
Eight cases of tumors or
ulcers were described in
ancient Egyptian text on trauma surgery.
Tumors were treated by
cauterization with a “fire
drill.”
400 BC:
Hippocrates proposed the Humoral Theory of
Medicine and attributed cancer to an excess of black bile. He
believed the cancer should be left alone,
because those who got treatment did not live as long as those who
were untreated.
168 BC:
Galen, a Roman physician, believed
advanced tumors should be
operated on by cutting around
the affected area.
1846 AD:
Anesthesia becomes
available and surgery
becomes more prominent.
Late 1800’s:
Surgeons perfected procedures to
remove parts of affected tissues, such
as mastectomies (removal of the entire breast and lymphatic system of the breast) to prevent outward
invasion.
1870-1890:
Thomas Beatson discovered that
estrogen stimulates breast cancer,
providing a foundation for
hormone therapy.
1893:
Coley’s Toxins were administered
as a vaccine to cancer patients. The idea that the immune system could be used to help fight cancer was pioneered.
1890’s:
1895: Wilhelm Rontgen discovered x-rays, which helped in the detection of
tumors.
1899: The first successful treatment
of cancer with radiation from x-rays.
Radiation therapy begins.
1930’s-1940’s:
1939: Charles Huggins discovered that hormones were
important for the growth of certain cancers, further
paving the way for hormone therapies.
1941: Diethylstilbestrol, a synthetic estrogen,
was found to be effective in treating
prostate cancer.
1946:
The first chemotherapy was discovered by Louis
Goodman. Nitrogen mustards, used in WWII chemical
warfare, were found to be useful as chemotherapeutic
agents against cancer.
1970’s:
Less extensive surgery was shown
to be equally as effective. Also, 3D radiation delivery
was developed with CT, allowing for more accurate
radiation dosing.
Scientists identified a mutation in the
Philadelphia chromosome as the
genetic cause of chronic myelogenous
leukemia (CML).
1976:
The first oncogene was discovered by
Harold E. Varmus and J.
Michael Bishop.
1980’s:
Biological therapy and
immunotherapy expanded, as
interferon was found to be able to
treat cancer.
1995:
DNA microarrays were developed to
measure gene expression. This led to
the possibility of targeted therapy, or targeting genes and processes directly involved in cancer
initiation and metastases.
Late 1990’s to early 2000’s:
Monoclonal antibodies against
tumor antigens were approved by the FDA to treat certain cancers.
2001: The first targeted anti-
cancer therapy, against CML, was
approved.
2010:
Sipuleucel-T (a cancer vaccine that
boosts the immune system) was approved to
treat prostate cancer.
A Timeline of Pioneering Cancer Treatments
3000 BC 400 BC 168 BC 1846 AD Late 1800s 1870-1890 1893 1895-1899 1930-1940 1946 1970’s 1976 1980’s 1995 1997-2006 2010
25/01/2019
2
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp4
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp5
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp6
25/01/2019
3
Hormonaal gevoelige tumoren
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp7
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp8
Hormonaal gevoelige tumoren
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp9
Hormonaal gevoelige tumoren
25/01/2019
4
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp10
80% van de borstCa bezit
hormonale receptoren
Hormonaal gevoelige tumoren
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp11
Hormonale Therapie
hypothalamus Hypophyse
LHRH
25/01/2019
5
Hormonale Therapie
Ovarium
hypothalamus
Premenopausaal
Hypophyse
LHRH
Gonadotrophines
FSH + LH
Hormonale Therapie
Oestrogenen
Progesterone
Ovarium
hypothalamus
Premenopausaal
Hypophyse
LHRH
Gonadotrophines
FSH + LH
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp15
25/01/2019
6
Hormonale Therapie
Oestrogenen
Progesterone
Ovarium
hypothalamus
Premenopausaal
Hypophyse
LHRH
LHRH agonisten
(Gosereline / Zoladex) (1600 €) 1995
Oöphorectomie (353 €) 1896
Gonadotrophines
(FSH + LH)
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp16
Castratie / Ovariële ablatieBij de “bron” - enkel zinvol bij premenopauzale vrouwen
• Heelkundig : ovariëctomie
• (Radiotherapie - Radiosterilisatie)
• ChemischLHRH agonisten “overdrive inhibitie” van de hypophyseGosereline (Zoladex®) 3,6 mg SC q28d
Borstcarcinoom : Castratie
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp17
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp18
25/01/2019
7
Een castratie leidt uiteraard wel tot een vroegtijdige menopauze…
Borstcarcinoom : Castratie
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp19
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp20
25/10/2010 A Bols Hormonale therapie KHBO 21
25/01/2019
8
25/10/2010 A Bols Hormonale therapie KHBO 22
25/10/2010 A Bols Hormonale therapie KHBO 23
Bij postmenopauzale vrouwen is het echter zo dat er nog steeds belangrijke hoeveelheden estrogenen “perifeer” geproduceerd worden …
Borstcarcinoom : Aromatase inhibitoren
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp24
25/01/2019
9
Hormonale Therapie
Oestrogenen
Progesterone
Ovarium
hypothalamus
Premenopausaal
Hypophyse
LHRH
LHRH agonisten
(Gosereline / Zoladex) (1600 €) 1995
Oöphorectomie (353 €) 1896
Gonadotrophines
(FSH + LH)
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp25
Hormonale Therapie
Progesterone
Androgenen Oestrogenen
hypothalamus Hypophyse
LHRH
Pre/postmenopausaal
ACTH
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp26
Hormonale Therapie
Progesterone
Androgenen Oestrogenen
hypothalamus Hypophyse
LHRH
Pre/postmenopausaal
ACTH
Oestrogeen receptor blokkers
• (1) SERM : Tamoxifen (Nolvadex) (80 €) 1977
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp27
25/01/2019
10
Hormonale Therapie
Progesterone
Androgenen Oestrogenen
hypothalamus Hypophyse
LHRH
Pre/postmenopausaal
ACTH
Oestrogeen receptor blokkers
• (1) SERM : Tamoxifen (Nolvadex) (80 €) 1977
• (3) SERD : Fulvestrant (Faslodex) (3750 €) 2002
(4) Progesterone derivaten• Medroxyprogesterone (Provera)
• Megestrol acetaat (Megace) (250 €)
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp28
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp29
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp30
SERM : Selective Estrogen Receptor Modulator
25/01/2019
11
SERM : Tamoxifen
SERMSelective Estrogen Receptor ModulatorsPartiële antagonisten/agonisten
Tamoxifen (Nolvadex®) 20 mg PO qd(Toremifen (Fareston®))(Raloxifen (Evista®))
SERDSelective Estrogen Receptor Downregulators“Zuivere” antagonisten
Fulvestrant (Faslodex®) 500 mg (2 amp) IM q28d
Borstcarcinoom : Estrogeen Receptorblok
Hormonale Therapie
Progesterone
Androgenen Oestrogenen
hypothalamus Hypophyse
LHRH
Pre/postmenopausaal
ACTH
Oestrogeen receptor blokkers
• (1) SERM : Tamoxifen (Nolvadex) (100 €) 1977
• (3) SERD : Fulvestrant (Faslodex) (6000 €) 2002
(4) Progesterone derivaten• Medroxyprogesterone (Provera)
• Megestrol acetaat (Megace) (500 €)
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp33
25/01/2019
12
De derde manier – enkel mogelijk bij postmenopauzale vrouwen - is een blokkering van het aromatase enzymedat verantwoordelijk is voor de conversie van de androgenen naar oestrogenen
Anastrozole (Arimidex®) 1 mg qd
Letrozole (Femara®) 2,5 mg qd
Exemestane (Aromasin®) 25 mg qd
Borstcarcinoom : Aromatase inhibitoren
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp34
Hormonale Therapie
Progesterone
Androgenen Oestrogenen
Aromatase
hypothalamus Hypophyse
LHRH
Pre/postmenopausaal
ACTH
(2) Aromatase Inhibitoren (350-400 €) 1995
Anastrozole (Arimidex)
Exemestane (Aromasin)
Letrozole (Femara)19/01/2019 Dr Alain Bols
Verpleegkundig congres oncologie
De Valkaart Oostkamp35
Borstcarcinoom : Aromatase inhibitoren
Federman DD. The Adrenal. In: Dale DC, Federman DD, eds. Scientific American Medicine.
New York, NY: Scientific American Inc.; 1997.
Cortisol AndrostenedioneAldosterone
Testosterone
Estrone Estradiol
Cholesterol
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp36
25/01/2019
13
Aromatase inhibitoren
Grosso modo komt dit op hetzelfde neer als voor het borstcarcinoom
Prostaatcarcinoom
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp38
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp39
25/01/2019
14
Prostaatcarcinoom
hypothalamus
ACTH
Bijnieren
Hypophyse
Testosterone
Steroïden Testosterone
Perifere conversie
Testikel
Gonadotrophines
(FSH + LH)
LHRH
Prostaatcarcinoom
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp40
Prostaatcarcinoom
(Free)
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp41
Prostaatcarcinoom
hypothalamus
ACTH
Bijnieren
Hypophyse
Testosterone
Steroïden Testosterone
Perifere conversie
Testikel
Gonadotrophines
(FSH + LH)
LHRH
Prostaatcarcinoom
LHRH-agonist/antagonist
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp42
25/01/2019
15
Prostaatcarcinoom
hypothalamus
ACTH
Bijnieren
Hypophyse
Testosterone
Steroïden Testosterone
Perifere conversie
Testikel
Gonadotrophines
(FSH + LH)
LHRH
Prostaatcarcinoom
LHRH-agonist/antagonist
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp43
Castratie Bij de “bron”
• Heelkundig
• (Radiotherapie)
• ChemischLHRH agonisten “overdrive inhibitie” van de hypophyse
LHRH antagonisten
Prostaatcarcinoom : Castratie
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp44
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp45
25/01/2019
16
25/10/2010 A Bols Hormonale therapie KHBO 46
DyslipidemieCardiovasculair
25/01/2019
17
Depressie – FatigueMood Swings
Sarcopene obesitas
Diabetes mellitus
25/01/2019
18
Prostaatcarcinoom
hypothalamus
ACTH
Bijnieren
Hypophyse
Testosterone
Steroïden Testosterone
Perifere conversie
Testikel
Gonadotrophines
(FSH + LH)
LHRH
Prostaatcarcinoom
Testosteronreceptor
blokkers
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp52
LHRH-agonist/antagonist
Bicalutamide (Casodex®) 50 mg PO qd 500€
Flutamide (Eulexin®) 250 mg PO qd 111€
Prostaat: TestosteroneReceptorblok
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp53
Prostaat: Interferentie met aanmaakproces van testosterone
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp54
25/01/2019
19
Prostaatcarcinoom
hypothalamus
ACTH
Bijnieren
Hypophyse
Testosterone
Steroïden Testosterone
Perifere conversie
Testikel
Gonadotrophines
(FSH + LH)
LHRH
Prostaat: Interferentie met aanmaakproces van testosterone
Abiraterone (36 000 €) 2012
LHRH-agonist/antagonist
Inhibitie in het syntheseproces van testosterone nml door blokkeren van het CYP17A1 (17α-hydroxylase/17,20 lyase)
Abiraterone Zytiga® 1000 mg qd 36000 €
Prostaat: Interferentie met aanmaakproces van testosterone
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp56
Prostaatcarcinoom
hypothalamus
ACTH
Bijnieren
Hypophyse
Testosterone
Steroïden Testosterone
Perifere conversie
Testikel
Gonadotrophines
(FSH + LH)
LHRH
Prostaat: Interferentie met aanmaakproces van testosterone
Abiraterone
(36 000 €) 2012
LHRH-agonist/antagonist
Testosteronreceptor
blokkers
Enzalutamide
(36 000 €) 2013
25/01/2019
20
Inhibitie in het syntheseproces van testosterone nml door blokkeren van het CYP17A1 (17α-hydroxylase/17,20 lyase)
Enzalutamide Xtandi® 1000 mg qd 36000 €
Enzalutamide (Xtandi®) :Een nieuwe en krachtigere androgen-receptor inhibitor
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp58
Chemische CastratieLHRH agonisten 600€
Triptoreline Decapeptyl® 3,75 mg IM q28d - 11,25 mg IM q3m
LHRH antagonisten 1200€
Degarelix Firmagon® 80 mg SC q28d (opstartdosis 120 mg 2 amp SC)
Hormonale Testosterone ReceptorblokBicalutamide Casodex® 50 mg PO qd 500 €
Enzalutamide Xtandi® 160 mg PO qd 36 000 €
Blokkering synthese testosteroneAbiraterone Zytiga® 1000 mg PO qd 36 000 €
Prostaatcarcinoom : Inhibitie van hormonale pathway
19/01/2019 Dr Alain BolsVerpleegkundig congres oncologie
De Valkaart Oostkamp59
