Prostate cancer medical therapy
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
|
Prostate cancer Microchapters |
|
Diagnosis |
|---|
|
Treatment |
|
Case Studies |
|
Prostate cancer medical therapy On the Web |
|
American Roentgen Ray Society Images of Prostate cancer medical therapy |
|
Risk calculators and risk factors for Prostate cancer medical therapy |
Overview
Medical Therapy
Radiation therapy
- Radiotherapy uses ionizing radiation to kill prostate cancer cells. When absorbed in tissue, ionizing radiation such as Gamma and x-rays damage the DNA in cells, which increases the probability of apoptosis.
- Radiation therapy is commonly used in prostate cancer treatment
- It may be used instead of surgery or after surgery in early stage prostate cancer. Radiation therapy appears to cure small tumors that are confined to the prostate just about as well as surgery.
- In advanced stages of prostate cancer, radiation is used to treat painful bone metastases.
- Radiation therapy is often offered to men whose medical problems make surgery more risky.
- Two different kinds of radiation therapy are used in prostate cancer treatment:
Side effects of radiation therapy
- Both types of radiation therapy
Hormonal therapy
- Hormonal therapy uses medications or surgery to block prostate cancer cells from getting dihydrotestosterone (DHT), a hormone produced in the prostate and required for the growth and spread of most prostate cancer cells. Blocking DHT often causes prostate cancer to stop growing and even shrink.
- Hormonal therapy for prostate cancer targets the pathways the body uses to produce DHT. A feedback loop involving the testicles, the hypothalamus, and the pituitary, adrenal, and prostate glands controls the blood levels of DHT. First, low blood levels of DHT stimulate the hypothalamus to produce gonadotropin releasing hormone (GnRH). GnRH then stimulates the pituitary gland to produce luteinizing hormone (LH), and LH stimulates the testicles to produce testosterone. Finally, testosterone from the testicles and dehydroepiandrosterone from the adrenal glands stimulate the prostate to produce more DHT. Hormonal therapy can decrease levels of DHT by interrupting this pathway at any point.
- However, hormonal therapy rarely cures prostate cancer because cancers which initially respond to hormonal therapy typically become resistant after one to two years. Hormonal therapy is therefore usually used when cancer has spread from the prostate.
- It may also be given to certain men undergoing radiation therapy or surgery to help prevent return of their cancer.[3]
- There are several forms of hormonal therapy:
- Orchiectomy
- Antiandrogens
- GnRH antagonists suppress the production of LH directly, while GnRH agonists suppress LH through the process of downregulation after an initial stimulation effect. Abarelix is an example of a GnRH antagonist, while the GnRH agonists include leuprolide, goserelin, triptorelin, and buserelin. Initially, GnRH agonists increase the production of LH. However, because the constant supply of the medication does not match the body's natural production rhythm, production of both LH and GnRH decreases after a few weeks.[4]
- A very recent Trial I study (N=21) found that Abiraterone Acetate caused dramatic reduction in PSA levels and Tumor sizes in aggressive end-stage prostate cancer for 70% of patients. This is prostate cancer that resists all other treatments (e.g., castration, other hormones, etc.). Officially the impacts on life-span are not yet known because subjects have not been taking the drug very long. Larger Trial III Clinical Studies are in the works. If successful an approved treatment is hoped for around 2011.[5][6]
=Side effects
Each treatment has disadvantages which limit its use in certain circumstances. Although orchiectomy is a low-risk surgery, the psychological impact of removing the testicles can be significant. The loss of testosterone also causes
- hot flashes
- weight gain
- loss of libido
- gynecomastia
- osteoporosis
Chemotherapy
- Chemotherapy may be offered to slow disease progression and postpone symptoms.
- The most commonly used regimen combines the chemotherapeutic drug liste below:
- docetaxel with a
- corticosteroid
Bisphosphonates
Bisphosphonates such as zoledronic acid have been shown to delay skeletal complications such as fractures or the need for radiation therapy in patients with hormone-refractory metastatic prostate cancer.[8]
Analgesic
Bone pain due to metastatic disease is treated with opioid. Pain relievers such as morphine and oxycodone
Androgen ablation therapy
In 1941, Charles Huggins reported that androgen ablation therapy causes regression of primary and metastatic androgen-dependent prostate cancer.[9] Androgen ablation therapy causes remission in 80-90% of patients undergoing therapy, resulting in a median progression-free survival of 12 to 33 months. After remission an androgen-independent phenotype typically emerges, where the median overall survival is 23–37 months from the time of initiation of androgen ablation therapy.[10] The actual mechanism contributes to the progression of prostate cancer is not clear and may vary between individual patient. A few possible mechanisms have been proposed.[11] Scientists have established a few prostate cancer cell lines to investigate the mechanism involved in the progression of prostate cancer. LNCaP, PC-3, and DU-145 are commonly used prostate cancer cell lines. The LNCaP cancer cell line was established from a human lymph node metastatic lesion of prostatic adenocarcinoma. PC-3 and DU-145 cells were established from human prostatic adenocarcinoma metastatic to bone and to brain, respectively. LNCaP cells express androgen receptor (AR), however, PC-3 and DU-145 cells express very little or no AR. AR, an androgen-activated transcription factor, belongs to the steroid nuclear receptor family. Development of the prostate is dependent on androgen signaling mediated through AR, and AR is also important during the development of prostate cancer. The proliferation of LNCaP cells is androgen-dependent but the proliferation of PC-3 and DU-145 cells is androgen-insensitive.Elevation of AR expression is often observed in advanced prostate tumors in patients.[12][13] Some androgen-independent LNCaP sublines have been developed from the ATCC androgen-dependent LNCaP cells after androgen deprivation for study of prostate cancer progression. These androgen-independent LNCaP cells have elevated AR expression and express prostate specific antigen upon androgen treatment. Androgens paradoxically inhibit the proliferation of these androgen-independent prostate cancer cells.[14][15][16] Androgen at a concentration of 10-fold higher than the physiological concentration has also been shown to cause growth suppression and reversion of androgen-independent prostate cancer xenografts or androgen-independent prostate tumors derived in vivo model to an androgen-stimulated phenotype in athymic mice.[17][18] These observation suggest the possibility to use androgen to treat the development of relapsed androgen-independent prostate tumors in patients. Oral infusion of green tea polyphenols, a potential alternative therapy for prostate cancer by natural compounds, has been shown to inhibit the development, progression, and metastasis as well in autochthonous transgenic adenocarcinoma of the mouse prostate (TRAMP) model, which spontaneously develops prostate cancer.[19]
References
- ↑ Lawton, CA (1991). "Long-term treatment sequelae following external beam irradiation for adenocarcinoma of the prostate: analysis of RTOG studies 7506 and 7706". Int J Radiat Oncol Biol Phys. 21 (4): 935–9. PMID 1917622. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) - ↑ Brenner, DJ (2000). "Second malignancies in prostate carcinoma patients after radiotherapy compared with surgery". Cancer. 88 (2): 398–406. doi:10.1002/(SICI)1097-0142(20000115)88:2<398::AID-CNCR22>3.0.CO;2-V. PMID 10640974. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) - ↑ Robson, M (1996). "How is androgen-dependent metastatic prostate cancer best treated?". Hematol Oncol Clin North Am. 10 (3): 727–47. doi:10.1016/S0889-8588(05)70364-6. PMID 8773508. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) Review. - ↑ Loblaw, DA (2004). "American Society of Clinical Oncology recommendations for the initial hormonal management of androgen-sensitive metastatic, recurrent, or progressive prostate cancer". J Clin Oncol. 22 (14): 2927–41. doi:10.1200/JCO.2004.04.579. PMID 15184404. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) Erratum in: J Clin Oncol. 2004 November 1;22(21):4435. - ↑ de Bono, Johann (2004). "Phase I Clinical Trial of a Selective Inhibitor of CYP17, Abiraterone Acetate, Confirms That Castration-Resistant Prostate Cancer Commonly Remains Hormone Driven". J Clin Oncol: online. doi:10.1200/JCO.2007.15.9749. PMID 15184404. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) Erratum in: J Clin Oncol. Early Release, published ahead of print July 21, 2008 - ↑ Richard Warry (July 22, 2008). "Drug for deadly prostate cancer". BBC. Retrieved 2008-07-23.
- ↑ Tannock, IF (2004). "Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer". N Engl J Med. 351 (15): 1502–12. doi:10.1056/NEJMoa040720. PMID 1547021. Unknown parameter
|month=ignored (help); Unknown parameter|coauthors=ignored (help) - ↑ Saad F, Gleason DM, Murray R, Tchekmedyian S, Venner P, Lacombe L, Chin JL, Vinholes JJ, Goas JA, Chen B (2002). "A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma". J Natl Cancer Inst. 94 (19): 1458–68. PMID 12359855.
- ↑ Huggins C, Steven RE and Hodges CV, Studies on prostatic cancer. Arch. Sug. 43:209–223, 1941.
- ↑ Hellerstedt BA and Pienta KJ, The current state of hormonal therapy for prostate cancer, CA Cancer J. Clin. 52: 154–179, 2002.PMID 12018929
- ↑ Feldman BJ, Feldman D. The development of androgen-independent prostate cancer. Nat Rev Cancer. 2001 Oct;1(1):34–45. PMID 11900250
- ↑ Linja MJ, Savinainen KJ, Saramaki OR, Tammela TL, Vessella RL, Visakorpi T. Amplification and overexpression of androgen receptor gene in hormone-refractory prostate cancer. Cancer Res. 2001 May 1;61(9):3550–5. PMID 11325816
- ↑ Ford OH 3rd, Gregory CW, Kim D, Smitherman AB, Mohler JL. Androgen receptor gene amplification and protein expression in recurrent prostate cancer. J Urol. 2003 Nov;170(5):1817–21.PMID 14532783
- ↑ Kokontis J, Takakura K, Hay N, Liao S. Increased androgen receptor activity and altered c-myc expression in prostate cancer cells after long-term androgen deprivation. Cancer Res. 1994 March 15;54(6):1566–73. PMID 7511045
- ↑ Umekita Y, Hiipakka RA, Kokontis JM, Liao S. Human prostate tumor growth in athymic mice: inhibition by androgens and stimulation by finasteride. Proc Natl Acad Sci U S A. 1996 October 15;93(21):11802-7. PMID 8876218
- ↑ Kokontis JM, Hsu S, Chuu CP, Dang M, Fukuchi J, Hiipakka RA, Liao S. Role of androgen receptor in the progression of human prostate tumor cells to androgen independence and insensitivity. Prostate. 2005 December 1;65(4):287-98. PMID 16015608
- ↑ Chuu CP, Hiipakka RA, Fukuchi J, Kokontis JM, Liao S. Androgen causes growth suppression and reversion of androgen-independent prostate cancer xenografts to an androgen-stimulated phenotype in athymic mice. Cancer Res. 2005 March 15;65(6):2082–4. PMID 15781616
- ↑ Chuu CP, Hiipakka RA, Kokontis JM, Fukuchi J, Chen RY, Liao S. Inhibition of tumor growth and progression of LNCaP prostate cancer cells in athymic mice by androgen and liver X receptor agonist. Cancer Res. 2006 July 1;66(13):6482–6. PMID 16818617
- ↑ Gupta S, Hastak K, Ahmad N, Lewin JS, Mukhtar H. Inhibition of prostate carcinogenesis in TRAMP mice by oral infusion of green tea polyphenols. Proc Natl Acad Sci U S A. 2001 August 28;98(18):10350-5. PMID 11504910