제 7장. 비뇨기계 항암제 사용법 편집하기 (부분)

==Metastatic Prostate Cancer==
===Androgen deprivation therapy===

- Basics of hormonal control of the prostate

- Therapeutic approaches to androgen deprivation therapy

1) Bilateral orchiectomy

:<nowiki>:</nowiki> Within 24hours of surgical castration, testosterone levels are reduced by more than 90%

2) Inhibition of LHRH

:(1) LHRH agonist
:synthetic analogs of native LHRH
:initial exposure to agonists of LHRH results in a flare of LH testosterone levels
:<nowiki>:</nowiki> known as the ‘testosterone surge’ or ‘flare up’ phenomenon (begins within 2-3days of the first injection and lasts through approximately the first week of therapy)
:<nowiki>:</nowiki> result in a severe, life-threatening exacerbation of symptoms
:→ co-administration of an antiandrogen (for only 21-28 days)
:Goserelin acetate (Zoladex): 3.6mg sc monthly
:Leuprorelin acetate (Leuplin): 3.75mg sc monthly
:Leuprolide acetate: 7.5mg sc monthly

3) Antiandrogens
:Compete with testosterone and DHT for binding sites on their receptors in the prostate cell nucleus: promoting apoptosis and inhibiting prostate cancer growth
:- Steroidal antiandrogens
:<nowiki>:</nowiki> Cyproterone Acetate, Megesterol acetate, medroxyprogesterone acetate
:- Non-steroidal or pure antiandrogen
:<nowiki>:</nowiki> Flutamide (250mg tid), bicalutamide (50mg po daily), nilutamide (150mg daily)

4) Antiandrogen withdrawal phenomenon

:정의: experience a decline in PSA level, objective
:responses with the withdrawal of the antiandrogen from the combination with LHRH agonist
:- Declines in PSA level are seen
:→ within 4weeks with flutamide withdrawal
:→ within 6weeks with bicalutamide, nilutamide withdrawal
:- Declines in PSA level of more than 50% (15-30%), and median duration of 3.5-5months

===Castration resistant prostate cancer===

1) CRPC without Symptom or minimal Symptom
:(1) Observation
:(2) 2nd hormonal Tx
:- Ketoconazole: 200mg tid+prednisolone 5mg bid
::그외 Alternative antiandrogen, High dose antiandrogen, Estrogen, Glucocorticoid 등이 있음.

2) CRPC with Symptom
:(1) Docetaxel+prednisolone
::Docetaxel 75mg/m2+P/S 200ml IV for 1hr Day1+PRD 5mg bid po q 3wks
::RR: 70% (PR: 38%, CR: 32%), median survival: 12.7 mo response rate of reduction in PSA 45%
::- Ref) NEJM 2004;351:1502-1512

<nowiki>**</nowiki> Docetaxel 투여시 전처치 및 주의사항
:- Prevention of hypersensitive reaction
1) dexamethasone 20mg iv before 30min of chemotherapy(Day1)
2) dexamethasone (8mg orally twice daily, Day 2-3)
:steroid 전처치: hypersensitivity 감소, fluid retention 감소, asthenia 감소

3) pheniramine 1x iv

4) ranitidine 50mg iv

- Dose reduction from toxicity

1) 20% dose reduction:
:prolonged grade 4 neutropenia (>7days)
:grade 4 thrombocytopenia
:grade ≥2 liver toxicity
:grade ≥3 diarrhea
:grade ≥3 cutaneous toxicity

2) Discontinue
:grade > 2 renal toxicity: Clcr < 60ml/min
:grade 3 liver toxicity
:grade ≥ 3 neuropathy
:grade 4 cutaneous toxicity
:grade 3 anaphylactoid reaction

<nowiki>*</nowiki> Docetaxel chemoTx 예시 (OPD)

:1. Prehydration P/S 500cc (300cc/hr)
:2. dexamethasone 10mg iv
:3. metoclopramide 10mg iv
:4. chemo
::Docetaxel 75mg/m2+P/S 200cc (200cc/hr)
:5. posthydration P/S 500cc (300cc/hr)
:6. med) solondo (prednisolone) 5mg bid for 21days PRN med
:(2) Mitoxantrone+prednisolone (이 regimen은 pain palliation이 목적임.)
::Mitoxantrone (Mitron) 12mg/m2+P/S 100ml IV Day1+PRD 5mg BID for 21days
::Ref> JCO 1996;14:1756

<nowiki>**</nowiki> 새로운 약제들

1) Abiraterone acetate, androgen synthesis inhibitor (CYP 17 inhibitor)- CRPC, docetaxel 사용 전, 혹은 후 Abiraterone acetate 1,000mg once a day+prednisolone 5mg bid
:OS: 14.8 month PFS: 5.6 month
:Ref> NEJM 2011;364:1995, 2013;368;138

2) Enzalutamide (MDV 3,100), New androgen receptor inhibitors - CRPC, docetaxel fail 후에 Enzalutamide 160mg once a day
:OS: 18.4 month
:Ref> NEJM 2012;367:1187

3) Cabazitaxel- CRPC, docetaxel fail 후 

:Cabazitaxel 25mg/m2 iv over 1hr every 3weeks+prednisolone 5mg bid
:OS: 15.1 month, PFS: 2.8 month
:Ref> Lancet 2010;376:1147

<nowiki>**</nowiki> Spinal cord compression
:Dexamethsone 10mg loading after 4mg q 6hr+RT