hormone therapy in cancer for md pharmacology students

1. HORMONES IN
CANCER TREATMENT
DR GAUTAM PANDA
2ND YEAR PG STUDENT

2. CONTENTS
• INTRODUCTION
• GLUCOCORTICOID RECEPTOR
AGONISTS
• SERMS
• SERDS
• AIS
• PROGESTERONE RECEPTOR
AGONISTS
• GnRH ANALOGUES
• NONSTEROIDAL ANDROGEN
RECEPTOR ANTAGONISTS
• INHIBITORS OF STEROIDOGENESIS
• CONCLUSION

3. INTRODUCTION
• THE GROWTH OF CERTAIN CANCERS IS HORMONE DEPENDENT OR REGULATED
BY HORMONES
• THE CRITICAL ROLE OF ANDROGENS FOR PROSTATE CANCER GROWTH WAS
ESTABLISHED IN 1941 (DR CHARLES HUGGINS)

4. DRUG THERAPEUTIC USE CLINICAL
PHARMACOLOGY
GLUCOCORTICOID RECEPTOR AGONISTS
 DEXAMETHASONE
 PREDNISOLONE
 OTHERS
 Treatment of malignant hematologic
disorders (e.g. ALL, CLL, MM, HL,
NHL)
 Symptom palliation in various cancer
types (e.g. antiemetic, reduce edema
due to spinal cord compression, brain
metastases)
 Major Toxicities
 Cushing Syndrome
 Glucose Intolerance
 Immunosuppression
 Osteoporosis
 Psychosis
 Insomnia
 Acute reduction in dosing can lead
to recurrence of symptoms

5. DRUG THERAPEUTIC USE CLINICAL PHARMACOLOGY
SELECTIVE ESTROGEN RECEPTOR MODULATORS:
ANTI-ESTROGENS IN BREAST CANCER THERAPY
 TAMOXIFEN  Adjuvant therapy for pre- and
postmenopausal women with
HR(+) breast cancer
 Treatment of advanced or
metastatic HR(+) breast cancer
in pre- and postmenopausal
women
 Breast cancer prevention in pre-
and postmenopausal women
 SERM with partial agonist and antagonist action.
Antagonist of ER in breast.
 Long t1/2 .Steady-state levels reached 3-4 weeks.
 Some major toxicities due to ER agonist activity
(e.g., endometrial carcinoma, thromboembolic
events) or ER antagonist effects (e.g. vasomotor
symptoms, menstrual irregularities)
 Other adverse effects: cataracts
 TOREMIFENE  Metastatic HR (+) breast cancer  Pharmacology, clinical efficacy, and adverse effects
similar to those of tamoxifen
 Rare: Prolongs QT interval, increased risk of
torsades de pointes

6. TAMOXIFEN: MECHANISM OF ACTION
• COMPETITIVE INHIBITOR OF ESTROGENS
• BINDS TO THE ER
• ANTAGONIZES ESTROGEN-INDUCED PROLIFERATION OF HUMAN BREAST
CANCER
• ESTROGEN RECEPTOR (ER)
• ER ALPHA
• ER ΒETA

8. TAMOXIFEN: MECHANISM OF ACTION
• ANTAGONIST & PARTIAL AGONIST
• DIFFERENCES IN TISSUE DISTRIBUTION OF THE ER SUBTYPES
• FUNCTION & RELATIVE AMOUNTS OF DIFFERENT TRANSCRIPTIONAL
COREGULATOR PROTEINS

9. TAMOXIFEN: MECHANISM OF ACTION
• AGONIST EFFECTS
• UTERINE ENDOMETRIUM (ENDOMETRIAL HYPERTROPHY, VAGINAL
BLEEDING, ENDOMETRIAL CANCER)
• COAGULATION SYSTEM (THROMBOEMBOLISM)
• BONE METABOLISM (INCREASE IN BONE MINERAL DENSITY—SLOW
DEVELOPMENT OF OSTEOPOROSIS)
• LIVER (LOWERS TOTAL SERUM CHOLESTROL, LDL, LIPOPROTEINS)

10. TAMOXIFEN: ADME
• READILY ABSORBED AFTER ORAL ADMINISTRATION
• ONCE DAILY ADMINISTRATION
• PEAK CONCENTRATIONS AFTER 3-7 HOURS
• STEADY STATE LEVELS REACH AT 4-6 WEEKS
• TERMINAL T1/2 OF 7 DAYS

11. TAMOXIFEN: METABOLISM
• INVOLVES CYP3A4, CYP3A5 & CYP2D6
• N-DESMETHYL TAMOXIFEN
• CYP2D6 FORMS 4-HYDROXYTAMOXIFEN (MORE POTENT METABOLITE)
• 4-HYDROXY-N-DESMETHYLTAMOXIFEN (ENDOXIFEN)
• HIGH AFFINITY FOR ER

13. TAMOXIFEN: ELIMINATION
• ELIMINATION
• ENTREROHEPATIC CIRCULATION: GLUCURONIDES & OTHER METABOLITES
• MOSTLY EXCRETED IN STOOL
• EXCRETION IN THE URINE IS MINIMAL

14. TAMOXIFEN:THERAPEUTIC USES
• WOMEN WITH ER+ METASTATIC BREAST CANCER
• FOLLOWING PRIMARY EXCISION OF AN ER+ TUMOR AS AN ADJUVANT
TREATMENT TO PREVENT RECURRENCE AND EXTEND OVERALL SURVIVAL
• ADJUVANT THERAPY OF EARLY-STAGE BREAST CANCER
• THERAPY OF ADVANCED BREAST CANCER

15. TAMOXIFEN: THERAPEUTIC USES
• PREVENTION OF BREAST CANCER IN HIGH RISK PATIENTS
• STRONG FAMILY HISTORY
• PRIOR NONMALIGNANT BREAST PATHOLOGY
• REDUCES ONLY ER+ TUMORS, NOT ER-NEGATIVE TUMORS

16. TAMOXIFEN: TOXICITY
• VASOMOTOR SYMPTOMS (HOT FLASHES)
• ATROPHY OF THE LINING OF THE VAGINA
• MENSTRUAL IRREGULARITIES
• VAGINAL BLEEDING AND DISCHARGE
• PRURITUS VULVAE
• ENDOMETRIAL CANCER

17. TAMOXIFEN: TOXICITY
• THROMBOEMBOLIC EVENTS
• RETINAL DEPOSITS
• DECREASED VISUAL ACUITY
• CATARACTS

18. TOREMIFENE
• TRIPHENYLETHYLENE DERIVATIVE OF TAMOXIFEN
• SIMILAR PHARMACOLOGICAL PROFILE, CLINICAL EFFICACY AND SAFETY
• METASTATIC BREAST CANCER IN WOMEN WITH ER+ TUMORS OR OF UNKNOWN
RECEPTOR STATUS
• PROLONGS QT INTERVAL

19. NOVELANTIESTROGEN COMPOUNDS
TAMOXIFEN ANALOGUES
1. TOREMIFENE
2. DROLOXIFENE
3. IDOXIFENE
“FIXED-RING” COMPOUNDS
1. RALOXIFENE
2. BAZEDOXIFENE
3. LASOFOXIFENE
4. ARZOXIFENE
5. MIPROXIFENE
6. LEVORMELOXIFENE
SERDs
Pure Antiestrogens
1. FULVESTRANT

20. ENDOCRINE RESISTANCE
• INITIAL OR ACQUIRED
• LOSS OF ER EXPRESSION
• CHANGES IN COREGULATOR EXPRESSION
• HORMONE-INDEPENDENT ACTIVATION OF THE ER BY STRESS KINASE OR
GROWTH FACTOR-ACTIVATED CELLULAR KINASE PATHWAYS
• CROSS TALK BETWEEN THE ER AND THE HER2/NEU PATHWAY
• ESTROGEN DEPRIVATION THERAPY
• ACQUIRED ER MUTATIONS

21. DRUG THERAPEUTIC USE CLINICAL PHARMACOLOGY
SELECTIVE ESTROGEN RECEPTOR DOWNREGULATORS:
ANTIESTROGENS IN BREAST CANCER THERAPY
(PURE ANTIESTROGENS)
 FULVESTRANT
 ADVANCED OR
METASTATIC HR(+)
BREAST CANCER (+/-
CDK4/6 INHIBITORS) IN
POSTMENOPAUSAL
WOMEN WHO HAVE
PROGRESSED AFTER
ANTIESTROGEN THERAPY
 BINDS TO ER, BLOCKS ESTROGEN ACTION
AND CAUSES DEGRADATION OF THE ER
 NO ESTROGEN AGONIST EFFECTS
 IM LOADING THEN MONTHLY DOSING;
STEADY STATE ACHIEVED IN FIRST
MONTH
 SIDE EFFECTS: INJECTION SITE
REACTION, NAUSEA, WEAKNESS, BONE
AND BACK PAIN, FATIGUE, VASOMOTOR
SYMPTOMS, HEADACHE

22. FULVESTRANT
• ONLY FDA-APPROVED SERD
• SINGLE AGENT OR IN COMBINATION WITH PALBOCICLIB, (CDK4/6 INHIBITOR)
• POSTMENOPAUSAL WOMEN WITH HR+ METASTATIC BREAST CANCER AFTER
PROGRESSION ON FIRST-LINE ANTIESTROGEN THERAPY

23. FULVESTRANT: MECHANISM OF ACTION
• STEROIDAL ANTIESTROGEN
• BINDS TO THE ER (100 TIMES MORE AFFINITY THAN TAMOXIFEN)
• INHIBITS THE BINDING OF ESTROGEN
• INHIBITS RECEPTOR DIMERIZATION
• ALTERS THE RECEPTOR STRUCTURE---PROTEASOMAL DEGRADATION
• REDUCES THE NUMBER OF ER MOLECULES IN CELLS---ER DOWNREGULATION

24. FULVESTRANT: ADME
• IM, BIWEEKLY LOADING DOSES IN THE FIRST MONTH, THEN ONCE MONTHLY
• STEADY-STATE LEVELS ARE ACHIEVED WITHIN THE FIRST MONTH
• PEAK PLASMA CONCENTRATION IN 7 DAYS
• PLASMA 𝑇1/2 IS 40 DAYS
• HIGHLY LIPOPHILIC, RAPID DISTRIBUTION, EXTENSIVE PROTEIN BINDING

25. FULVESTRANT: METABOLISM
• SIMILAR TO STEROID METABOLISM
• OXIDATION
• AROMATIC HYDROXYLATION
• CONJUGATION
• CYP3A4

26. FULVESTRANT: TOXICITY
• NO ESTROGEN AGONIST ACTIVITY
• NAUSEA
• ASTHENIA
• PAIN
• HOT FLASHES
• ATHRALGIA, HEADACHE
• INJECTION SITE REACTION

27. DRUG THERAPEUTIC USE CLINICAL
PHARMACOLOGY
AROMATASE INHIBITORS:
ANTIESTROGEN IN BREAST CANCER THERAPY
 ANASTROZOLE,
LETROZOLE
(NONSTEROIDAL,
COMPETITIVE INHIBITORS)
 EXEMESTANE
(STEROIDAL, IRREVERSIBLE
INHIBITOR)
 ADJUVANT TREATMENT OF
POSTMENOPAUSAL WOMEN
WITH HR(+) BREAST CANCER
 TREATMENT OF
POSTMENOPAUSAL WOMEN
WITH HR(+) ADVANCED AND
METASTATIC BREAST CANCER
(+/-CDK4/6 INHIBITORS)
 BREAST CANCER
PREVENTION IN
POSTMENOPAUSAL WOMEN
 AIS SIGNIFICANTLY LOWER
ESTROGENS
 CONTRAINDICATED IN
PREMENOPAUSAL WOMEN
WITH OVARIAN FUNCTION
 MAJOR SIDE EFFECTS:
VASOMOTOR SYMPTOMS,
ATHRALGIA, LOSS OF BONE
MINERAL DENSITY,
OSTEOPOROSIS, FRACTURES,
VAGINAL DRYNESS,
DYSPAREUNIA

28. AROMATASE INHIBITORS
• STANDARD OF CARE FOR ADJUVANT TREATMENT OF POSTMENOPAUSAL WOMEN
WITH ER+ BREAST CANCER---INITIAL THERAPY OR AFTER TAMOXIFEN
• INITIAL TREATMENT OF METASTATIC HR+ BREAST CANCER, IN COMBINATION
WITH CDK4/6 INHIBITORS
• DISEASE THAT HAS PROGRESSED FOLLOWING TAMOXIFEN TREATMENT IN
POSTMENOPAUSAL WOMEN

30. AROMATASE INHIBITOR
• INCREASES GONADOTROPHIN PRODUCTION IN PREMENOPAUSAL WOMEN
• REDUCES THEIR ABILITY TO INHIBIT OVARIAN ESTROGEN PRODUCTION
• NOT EFFECTIVE IN PREMENOPAUSAL WOMEN WITHOUT ADDITIONAL OVARIAN
SUPPRESSION
• SUPPRESS MOST PERIPHERAL AROMATASE ACTIVITY IN POSTMENOPAUSAL
WOMEN—PROFOUND ESTROGEN DEPRIVATION

31. AROMATASE INHIBITORS
• CLASSIFIED AS 1ST, 2ND OR 3RD GENERATION
• 1ST & 2ND GENERATION AIS ARE NO LONGER USED
• TYPE 1 (STEROIDAL)
• STEROIDAL ANALOGUES OF ANDROSTENEDIONE
• BIND COVALENTLY AND IRREVERSIBLY (SAME SITE)
• AROMATASE INACTIVATORS

33. AROMATASE INHIBITORS
• TYPE 2
• NONSTEROIDAL
• BIND REVERSIBLY TO THE HEME GROUP OF THE CYP19 ENZYME
• REVERSIBLE INHIBITION

34. AROMATASE INHIBITORS: ANASTROZOLE
• BINDS COMPETITIVELY AND SPECIFICALLY TO THE HEME OF THE CYP19
• REDUCES TOTAL BODY ANDROGEN AROMATIZATION BY ˃95% AFTER 1 MONTH
• RAPIDLY ABSORBED ORALLY
• STEADY STATE IS ACHIEVED AFTER 7 DAYS OF REPEATED DOSING
• METABOLIZED BY
• N-DEALKYLATION
• HYDROXYLATION
• GLUCURONIDATION

35. AROMATASE INHIBITORS: ANASTRAZOLE
• ELIMINATION IS BY THE LIVER AND BILIARY TRACT
• ELIMINATION 𝑇1/2 IS 50 HOURS
• THERAPEUTIC USES
• UP-FRONT ADJUVANT THERAPY FOR 5-10 YEARS OR FOLLOWING TAMOXIFEN IN
POSTMENOPAUSAL WOMEN WITH EARLY-STAGE BREAST CANCER
• TREATMENT OF ADVANCED AND METASTATIC BREAST CANCER
• EARLY-STAGE BREAST CANCER—ANASTROZOLE IS SIGNIFICANTLY MORE EFFECTIVE THAN
TAMOXIFEN (TIME TO TUMOR RECURRENCE AND DECREASING THE ODDS OF A PRIMARY
CONTRALATERAL TUMOR)

36. AROMATASE INHIBITORS: ANASTROZOLE
• IN WOMEN WITH ER+/PR+ METASTATIC BREAST CANCER, ANASTROZOLE IS
SIGNIFICANTLY BETTER THAN TAMOXIFEN IN MEDIAN TIME TO DISEASE
PROGRESSION
• IN PREMENOPAUSAL WOMEN, COMBINED WITH OVARIAN SUPPRESSION
• IN WOMEN ˂35 YEARS OF AGE, AI USE IS ASSOCIATED WITH SIGNIFICANT
REDUCTION IN RISK OF RECURRENCE

37. ANASTRAZOLE: ADVERSE EFFECTS
• ESTROGEN DEPLETION
• IN POSTMENOPAUSAL WOMEN, COMPARED TO TAMOXIFEN, LOWER INCIDENCE
• HOT FLASHES
• VAGINAL BLEEDING
• VAGINAL DISCHARGE
• ENDOMETRIAL CANCER
• ISCHAEMIC CEREBROVASCULAR
EVENTS
• VENOUS THROMBOEMBOLIC
EVENTS
• DEEP VENOUS THROMBOSIS

38. ANASTROZOLE: ADVERSE EFFECTS
• HIGHER INCIDENCE OF
• ARTHRALGIAS
• VAGINAL DRYNESS
• SEXUAL DYSFUNCTION
• LOSS OF BONE MINERAL DENSITY (INCREASED FRACTURE RISK)
• BISPHOSPHONATES PREVENT AI-INDUCED LOSS OF BONE MINERAL DENSITY IN
POSTMENOPAUSAL WOMEN

39. LETROZOLE
• ORAL BIOAVAILABILITY—99.9%
• STEADY STATE PLASMA CONC ACHIEVED AFTER 2-6 WEEKS
• ELIMINATED BY THE KIDNEYS
• 𝑇1/2 IS 41 HOURS
• LETROZOLE IN COMBINATION WITH A CDK4/6 INHIBITOR HAS A BETTER
PROGRESSION-FREE SURVIVAL IN HR+ ADVANCED STAGE BREAST CANCER

40. EXEMESTANE
• MORE POTENT, ORALLY ADMINISTERED ANALOGUE OF ANDROSTENEDIONE
• IRREVERSIBLY INACTIVATES AROMATASE
• SUICIDE SUBSTRATE TYPE 1 INHIBITOR OF AROMATASE
• RAPIDLY ABSORBED, INCREASED AFTER A HIGH-FAT MEAL
• TERMINAL 𝑇1/2 IS 24 HOURS
• EXTENSIVELY METABOLIZED IN THE LIVER

41. EXEMESTANE
• 17-HYDROXYEXEMESTANE (WEAK ANDROGENIC ACTIVITY)
• EXCRETED IN THE URINE, NO DOSAGE ADJUSTMENT
• EVEROLIMUS WITH EXEMESTANE IN THE TREATMENT OF ADVANCED-STAGE
BREAST CANCER THAT HAS PROGRESSED ON NONSTEROIDAL TYPE 2 AIS

42. DRUG (DAILY
STANDARD DOSE)
THERAPEUTIC APPROACH IN DISEASE SETTING
CHEMOPREVENTION ADJUVANT THERAPY METASTATIC DISEASE
PREMENOPAUSE POSTMENOPAUSE PREMENOPAUSE POSTMENOPAUSE PREMENOPAUSE POSTMENOPAUSE
TAMOXIFEN
20MG PO
YES 5Y YES 5Y X X X X
RALOXIFEN
60MG PO
X YES 5Y X X X X
FULVESTRANT
500MG IM DAY 1,15,29
ONCE PER MONTH
X X X X X YES
ANASTROZOLE
1MG PO
X YES 5Y X YES (5-10
Y)
UP FRONT
OR AFTER
TAM
X YES
LETROZOLE
2.5MG PO
X X YES (5-10
Y)
UP FRONT
OR AFTER
X YES

43. DRUG THERAPEUTIC USE CLINICAL
PHARMACOLOGY
PROGESTERONE RECEPTOR AGONISTS
 MEGESTROL ACETATE
 TREATMENT OF
ENDOMETRIAL CANCER
AND RARELY OF BREAST
AND PROSTATE CANCER
 APPETITE STIMULANT IN
PATIENTS WITH AIDS OR
CANCER-ASSOCIATED
CACHEXIA
 ADVERSE EFFECTS: WEIGHT
GAIN, NAUSEA, VOMITING,
EDEMA, BREAKTHROUGH
BLEEDING, SHORTNESS OF
BREATH,
THROMBOPHLEBITIS,
PULMONARY EMBOLISM
 MEDROXYPROGESTERONE
ACETATE
 MANAGEMENT OF
ADVANCED STAGE
ENDOMETRIAL
CARCINOMA
 THERAPY OF
METASTATIC HORMONE-
DEPENDENT BREAST
CANCER
 ADVERSE EFFECTS: HOT
FLASHES, WEIGHT GAIN,
DEPRESSION, AMENORRHEA
 WITH LONG-TERM USE,
BONE LOSS IS POSSIBLE

44. DRUG THERAPEUTIC USE CLINICAL
PHARMACOLOGY
GONADOTROPIN-RELEASING HORMONE ANALOGUES:
CHEMICAL CASTRATION IN CANCER THERAPY
PROSTATE CANCER
 GnRH AGONISTS
1. LEUPROLIDE
2. GOSERELIN
3. HISTRELIN
4. TRIPTOLERIN
5. NAFARELIN
 ANDROGEN DEPRIVATION
THERAPY: DECREASES
PITUITARY RELEASE OF LH
AND FSH, DECREASES
TESTICULAR TESTOSTERONE
PRODUCTION
 TREATMENT OF ADVANCED
PROSTATE CANCER
 IN COMBINATION WITH
RADIATION THERAPY OR
SURGERY FOR MANAGEMENT
OF MODERATE-/HIGH-RISK
LOCALLY CONFINED PROSTATE
CANCER
 CAN CAUSE INITIAL
TESTOSTERONE SURGE AND
TUMOR FLARE.
 ADMINISTERED WITH
ANTIANDROGENS TO REDUCE
INITIAL SIDE EFFECTS FROM
TESTOSTERONE SURGE.
 SIDE EFFECTS RELATED TO LOW
TESTOSTERONE: VASOMOTOR
SYMPTOMS, LOSS OF LIBIDO,
OSTEOPOROSIS, FATIGUE,
IMPOTENCE, GYNAECOMASTIA,
LOSS OF MUSCLE MASS
 SMALL INCREASE IN RISK OF
DIABETES OR DEVELOPMENT OF
CARDIOVASCULAR DISEASE

45. PROSTATE CANCER
GnRH ANTAGONISTS:
1. DEGARELIX
(CETRORELIX)
 TREATMENT OF ADVANCED
PROSTATE CANCER
 CETRORELIX RARELY USED DUE
TO RISK OF ANAPHYLAXIS
 NO INITIAL TESTOSTERONE
SURGE; RAPID SUPPRESSION OF
SERUM TESTOSTERONE AND PSA
LEVELS
 SIDE-EFFECT PROFILE IN MEN
SIMILAR TO GnRH AGONISTS
BREAST CANCER
GnRH AGONIST:
1. GOSERELIN
2. LEUPROLIDE
 SUPPRESSION OF OVARIAN
ESTROGEN AND PROGESTERONE
PRODUCTION IN PRE- AND
PERIMENOPAUSAL WOMEN
 WITH ANTIESTROGENS AS
ADJUVANT THERAPY AND FOR
METASTATIC DISEASE
 ADVERSE EFFECTS DUE TO
HYPOESTROGENISM:
VASOMOTOR SYMPTOMS,
DECREASED LIBIDO,
OSTEOPOROSIS, TUMOR FLARE,
FATIGUE, VAGINAL DRYNESS,
DYSPAREUNIA

46. DRUG THERAPEUTIC USE CLINICAL PHARMACOLOGY
NONSTEROIDAL ANDROGEN RECEPTOR ANTAGONISTS:
ANTIANDROGENS IN PROSTATE CANCER THERAPY
 ENZALUTAMIDE  TREATMENT OF METASTATIC,
CRPC IN CONJUNCTION WITH ADT
FOLLOWING DOCETAXEL
THERAPY
 ADVERSE EFFECTS RELATED TO AR
ANTAGONISM: SEXUAL DYSFUNCTION,
GYNAECOMASTIA, BREAST PAIN,
FATIGUE, DIARRHEA, HEADACHE,
MUSCULOSKELETAL PAIN, VASOMOTOR
SYMPTOMS, HOT FLASHES
 RARE: SEIZURES (LIKELY DUE TO
CENTRAL “OFF-TARGET” EFFECTS)
 BICALUTAMIDE
 USED WITH GnRH ANALOGUES TO
TREAT METASTATIC CRPC
 ADVERSE EFFECTS SIMILAR TO
ENZALUTAMIDE
 FAVOURABLE TOXICITY AND
PHARMACOKINETIC PROFILE RELATIVE
TO FLUTAMIDE OR NILUTAMIDE

47.  FLUTAMIDE
 USED WITH GnRH ANALOGUES
TO TREAT METASTATIC CRPC
 ACTIVE METABOLITE:
HYDROXYFLUTAMIDE
 SIGNIFICANT HEPATOTOXICITY
POSSIBLE
 NILUTAMIDE
 USED WITH GnRH ANALOGUES
TO TREAT CRPC AFTER
PROGRESSION ON OTHER
ANTIANDROGENS
 RARE ADVERSE EFFECT:
INTERSTITIAL PNEUMONITIS

48. DRUG THERAPEUTIC USE CLINICAL PHARMACOLOGY
INHIBITORS OF STEROIDOGENESIS:
ANTIANDROGENS IN PROSTATE CANCER THERAPY
 ABIRATERONE
 TREATMENT OF ADVANCED
METASTATIC CRPC
 USED IN COMBINATION WITH
PREDNISONE (TO COMPENSATE FOR
ADRENAL INSUFFICIENCY INDUCED
BY ABIRATERONE)
 IRREVERSIBLY INHIBITS CYP17A1,
DECREASES TESTOSTERONE AND
OTHER ANDROGENS
 FLUID RETENTION, HYPERTENSION,
HYPOKALEMIA, HEPATOTOXICITY,
FATIGUE, JOINT SWELLING,
VASOMOTOR SYMPTOMS, DIARRHEA,
ARRHYTHMIA
 TAKE ON EMPTY STOMACH; FOOD
INCREASES UPTAKE ˃ 10-FOLD

49. CONCLUSION
• CANCER TREATMENT REGIMENS CHANGE TO REFLECT CONTINOUS ADVANCES
IN BASIC AND CLINICAL SCIENCE
• HORMONES AND RELATED AGENTS PLAY AN IMPORTANT ROLE IN THE THERAPY
OF HORMONE DEPENDENT CANCER

50. REFERENCES
• GOODMAN & GILMAN’S THE PHARMACOLOGICAL BASIS OF THERAPEUTICS, 13TH
EDITION
• DOWSETT M, ET AL. META-ANALYSIS OF BREAST CANCER OUTCOMESIN
ADJUVANT TRIALS OF AROMATASE INHIBITORS VERSUS TAMOXIFEN. J CLIN
ONCOL, 2010, 28:509-518
• BRODIE AM, NJAR VC. AROMATASE INHIBITORS AND THEIR APPLICATION IN
BREAST CANCER TREATMENT. STEROIDS, 2000, 65:171-179

51. “DON’T EVER LET SOMEBODY TELL YOU THAT YOU CAN’T DO
SOMETHING.
YOU GOT A DREAM, YOU GOTTA PROTECT IT.”
THANK YOU