212 Prostate Carcinoma
42. Prostate Carcinoma
42.1 Gerneral considerations
The majority of prostate carcinomas are adenocarcinomas. The following considerations apply to that histology .
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Stage grouping |
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Stage T N M Grade* |
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I T1a N0 M0 G 1 |
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II T1a N0 M0 G 2-4 T1b N0 M0 any G T1c N0 M0 any G T 1,2 N0 M0 any G |
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III T3 N0 M0 any G |
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IV T4 N0 M0 any G any T N1 M0 any G any T any N M1 any G |
* Histopathologic grading : G1 = well differentiated , G2= moderately differentiated, G3,4 = Poorly differentiated, undifferentiated
Radical prostatectony or radiotherapy are definitive treatment for organ-confined, early stage prostate cancer . Adjuvant hormonal therapy has been found to delay disease progression, and to increase disease-free and overall survival when given after surgery or radiotherapy in selected patients. Neoasdjuvant hormonal therapy can improve disease-free survival and local control when given before radiotherapy, and decreases positive surgical margins when applied prior to radical prostatectomy. Suppression of androgen-production by medical or surgical castration is the accepted initial treatment of advanced prostate cancer. Radiotherapy also controls locally advanced disease. A number of treatment strategies have emerged for hormone-refractory , androgen-independent symptomatic disease, including secondary hormonal manipulations, radiotherapy and cytotoxic chemotherapy, which decrease PSA levels and improve quality of life.
Literature: for review e.g.
BAYOUMI et al, J. Natl. Cancer Inst. 92 (2000): 1731-1739 (cost-effectiveness of androgen suppression therapies)
CHAY and SMITH, Semin. Oncol. 28 (2001): 3-12 (adjuvant and neoduvant therapy)
CULINE and DROZ, Ann, Oncol. 11 (2000): 1523 1530 (chemotherapy)
DENIS and GRIFFITHS, Semin. Surg. Oncol. 18 (2000): 52-74 (hormonal treatment)
GINGRICH et al, Curr, Oncol. Rep. 3 (2001): 438-447 (gene therapy)
HAAS, Semin. Urol. Oncol. 19 (2001): 212-221 (chemotherapy)
HARRINGTON et al, J. Urol. 166 (2001): 1220-1233 (gene therapy)
HARRIS and REESE, Drugs 61 (2001): 2177-2192 (hormone-refractory prostate cancer)
HARRIS and SMALL, Expert Opin. Investig. Drugs 10(2001): 493-510 (hormonal treatment)
IWAMOTO and MAHER , Semin. Oncol. Nurs 17 (2001): 90 100 (radiation therapy)
KISH et al, Cancer Control 8 (2001): 487-495 (hormone-refractory prostate cnacer)
OH, Cancer 15 (Suppl 12) (2000): 3015-3021 (chemotherapy)
Prostate Carcinoma 213
OH and KANTOFF, J. Clin. Oncol. 17 (1999): 3664-3675 (locally advanced disease)
NEWLING, Eur. Urol. 39 (Suppl 1) (2001): 15-21 (timing of hormone therapy)
OLSON and PIENTA,Oncology 13(1999):1537-1550 (pain management) REESE, Hematol. Oncol. Clin. North Am. 15 (2001): 547 557 (new agents)
RINI and SMALL, Curr. Opin. Oncol. 13 (2001): 204-211 and Curr, Oncol. Rep. 3 (2001): 418-423
SLOVIN, Hematol. Oncol. Clin. North. Am. 15 (2001): 477-496 (vaccines)
Van POPPEL, Eur, Urol. 39 (Suppl1) (2001): 10 41 (neoadjuvant hormone therapy)
ZINCKE et al, J. Urol. 166 (2001): 2208 2215 (adjuvant hormone therapy)
42.2 Hormone (endocrine) therapy
42.2.1 LH-RH analogs (gonadotropin-releasing hormone agonists)
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Leuprorelin 3.75 mg s.c. once every month or 11.25 mg s.c. once every 3 months |
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Goserelin 3.6 mg s.c. once every months or 10.8 mg s.c. once every 3 months |
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Buserelin 6.6 mg s.c. every 2 months or 3x 0.5 mg s.c. d 1-7 followed by nasal application |
To prevent an initial rise of the androgen level, LH- RH analogs initially should be combined with an antiandrogen.
Literature: for review e.g.
COOK and SHERIDAN, Oncologist 5 (2000): 162 168
42.2.2. Non-sterodial antiandrogens
E.g. Flutamide
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Flutamide 750 mg p.o. daily * |
* Divided over 3 daily doses. For at least 6 weeks before evaluation of efficacy
and then until progression or unacceptable toxicity.
Literature:
FOSSA et al, J. Clin. Oncol. 19 (2001): 62-71 (phase III study of the EORTC Genitourinary Group to compare flutamide and prednisone in patients with prostate cancer symptomatically progressing after androgen- ablative therapy)
or
Bicalutamide
|
Bicalutamide 50 mg * p.o. daily or 150 mg ** p.o. daily |
* For combined androgen blockade
** For monotherapy
Literature: for review e.g.
ABRAHAMSON, Eur. Urol. 39 (Suppl 1) (2001): 22-28 KOLVENBAG et al, Urology 58 (Suppl 1) ( 2001): 16 23 SAROSDY, Anticancer Drugs 10 (1999): 791-796
214 Prostate Carcinoma
42.2.3. Combined androgen blockade
Combined androgen blockade with medical or surgical castration plus a nonsteroidal antiandrogen has been the subject of more than 20 randomized trials. It produces a modest overall and cancer specific survival advantage at five years, but is also associated with increased adverse events when compared to castration alone.
Literature:
SCHMITT et al, Urology 57 (2001): 727-732 PROSTATE CANCER TRIALISTS COLLABORATIVE GROUP, Lancet 355 (2000): 1491-1498.
42.2.4 Estrogens
Diethylstibestrol ( DES )
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Diethylstibestrol up to 3 mg p.o. daily |
Literature: for review e.g.
MALKOWICZ, Urology 58 ( Suppl 1) (2001): 108 113
Fosfestrol
|
Fosfestrol 600 1200 mg i.v. (short inf) d 1 10 For initial therapy followed by maintenance therapy with either 240 360 mg p.o. daily or 300 600 mn i.v. (short inf) 1-3 x weekly |
42.2.5 Progestins
E.g. Medroxyprogesterone acetate (MPA)
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MPA 1500 4000mg* p.o. daily |
* Start with the high dose, in case of response reduce every 4 weeks
Literature:
De VOOGT et al, J. Urol. 135 (1986): 303 307
42.3 Chemotherapy
42.3.1. #9; Single agent chemotherapy
Palliatively relevant activity is seen with mitoxantrone, anthracyclines, cyclophosphamide, estramustine phosphate, infusional mitomycin, infusional cisplatin, taxanes and suramin, amongst others ; e.g.
42.3.1.1 Mitoxantrone
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Mitoxantrone 12 mg/m2* i.v.(bolus) d1 |
To be repeated every 3 weeks
* Together with a corticosteroid (prednisone 5 mg b.i.d. p.o. daily or
hydrocortisone 30 mg in the morning + 10 mg in the evening p.o. daily). If nadir blood cell counts showed granulocytes < 0.5 x 109 per L / > 1.0 x 109 per L and / or platelets < 50 x 109 per L > 100 x 109 per L the mitoxantrone dose was reduced / increased by 2 mg/m2 respectively, on subsequent cycles.
Prostate Carcinoma 215
Literature:
KANTHOFF et al, j. Clin. Oncol. 17 (1999): 2509 2513 (randomized study B 9182 of the Cancer and Leukemia Group B comparing hydrocortisone with or without mitoxantrone)
OSOBA et al, J. Clin. Oncol. 17 (1999): 1654 1663 (quality of life in men with metastatic prostate cancer treated with prodnisone alone or mitoxantrone + prednisone)
TANNOCK et al, J. Clin. Oncol. 14 (1996): 1756 1764
42.3.1.2 Estramustine phosphate (EMP)
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Estramustine 560 - 840 mg* p.o. per day |
* Two x 2-3 capsules. Attention: EMP produces a complex with calcium when
dairy products or mineral water are partaken concomitantly, resulting in a
decrease in the absorption rate of EMP from the gut!
Literature: for review
KITAMURA, Int. J. Urol. 8 (2001): 33-36
42.3.1.3 Suramin
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Suramin 1000mg/m2 i.v. (2 h inf) d 1 then 400, 300, 250, 200 mg/m2 i.v. (1 h inf) d 2, 3, 4, 5 then 275 mg/m2 i.v.(1 h inf) d 8, 11, 15, 19, 22, 29,36,43,50, 57, 64, 71, 78 |
The dosing regimen is designed to achieve a sustained suramin plasma
concentration of 100-300 ΅g/ml. Patients also receive hydrocortisone 40 mg daily
p.o.
Literature:
SMALL et al, J. Clin. Onocl. 18 (2000): 1440 2450
42.3.2Combination chemotherapy
In phase II studies combinations of EMP with oral etoposide or taxanes or vinblastine showed higher response rates than single agent therapy; e.g.
42.3.2.1Vinblastine + EMP
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Vinblastine 4 mg/m2 i.v. weekly x 6 |
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Estramustine 600mg/m2 p.o. d 1-42 in 2-3 daily doses |
To be repeated every 8 weeks
Literature:
HUDES et al, J. Clin. Oncol. 17 (1999): 3160 3166 (phase III study of the Hoosier Oncology Group and Fox Chase Network comparing vinblastine vs vinblastine + EMP)
42.3.2.2. Docetaxel + EMP
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Docetaxel 70 mg/m2 i.v.(2 h inf) d 2 |
|
Estramustine 280mg p.o. (3 x daily) d 1-5 |
To be repeated every 3 weeks , with low-dose daily hydrocortisone
Literature:
SAVARESE et al, J. Clin. Oncol. 19 (2001): 2509 2516 (final report of phase II study CALGB 9780) WEITZMAN, J. Urol. 163 (2000): 834 837
216 Prostate Carcinoma
42.4 Bone-seeking radionuclides
For palliative management of prostate cancer metastatic to the skeleton.
Literature: for review e.g.
HAMDY and PAPAPOULOS, Semin. Nucl. Med. 31 (2001) : 62 68
42.4.1 Strontium 89
Literature:
CRAWFORD et al, Urology 44 (1994): 481 485 DICKIE and MACFARLANE, Australas, Radiol. 43 (1999): 476 479 JAGER et al, BJU Int. 86 (2000): 929 934 QUILTY et al, Radiother. Oncol. 31 (1994): 33 40
42.4.2 Samarium 153 EDTMP
Literature:
DICKIE and MACFARLANE, Australas, Radiol. 43 (1999): 476 479
SERAFINI et al, J. Clin. Oncol. 16 (1998): 1574 1581