Prostate cancer hormone-refractory

Diethylstilbestrol continues to be recommended in some centers as one of the agents of last resort when prostate cancer proves refractory to steroid hormones or androgen deprivation therapy has done all it can (1). In a Japanese study in which 16 patients were given a daily intravenous injection of diethylstilbestrol diphosphate 250 mg for 28 days, the short-term response was favorable and the drug was well tolerated (2). 

ABT-627 (Atrasentan) Abbott Laboratories, USA ETA receptor Hormone-refractory prostate cancer, stage IV (phase III)... 

Chemotherapy, with docetaxel and prednisone or docetaxel and estramustine, improves survival in patients with hormone-refractory prostate cancer. Patients with hormone-refractory prostate cancer should be considered for entry into clinical trials investigating new therapies for prostate cancer. 

Wang, A. and Zhang L. 2007. Effect of lycopene on proliferation and cell cycle of hormone refractory prostate cancer PC-3 cell line. Wei Sheng Yan Jiu 36 575-578. 

Pt(TV) Prodrugs. Platinum(IV) complexes have been widely studied as potential prodrugs that avoid the limitations of the cisplatin class of anticancer drugs. Indeed, the Pt(IV) compound satraplatin [Pt(cha)Cl2(OAc)2(NH3)] (cha, cyclohexylamine) is currently in clinical trials for treatment of hormone-refractory prostate cancer (Fig. 1) (22). Satraplatin is the first orally bioavailable platinum derivative under active clinical investigation and is particularly attractive because of the convenience of administration, milder toxicity profile, and lack of cross-resistance with cisplatin. These results are promising and support the idea that platinum(IV) complexes offer the opportunity to overcome some of the problems associated with cisplatin and its analogs. 

Bisphosphonates such as pamidronate and zoledronic acid may prevent skeletal morbidity, such as pathologic fractures and spinal code compression, when used for hormone-refractory prostate cancer in patients with clinically significant bone loss. Usual dosages are pamidronate, 90 mg every month, and zoledronic acid, 4 mg every 3 to 4 weeks. 

Docetaxel, 75 mg/m2 every 3 weeks, combined with prednisone, 5 mg twice daily, has been shown to prolong survival in hormone-refractory metastatic prostate cancer. The most common adverse events were nausea, alopecia, and myelosuppression. Docetaxel can also cause fluid retention and peripheral neuropathy. 

The combination of estramustine 280 mg by mouth three times daily on days 1 to 5 and docetaxel 60 mg/m2 on day 2 of a 21-day cycle also improves survival in hormone-refractory metastatic prostate cancer. Estramustine causes a decrease in testosterone and a corresponding increase in estrogen, which results in an increase in thromboembolic events, gynecomastia, and decreased libido. 

A Heidenreich, R von Knobloch, R Hofmann. Current status of cytotoxic chemotherapy in hormone refractory prostate cancer. Eur Urol 39 121—130, 2001. 

When CNS involvement occurs, the poor penetration of suramin and pentamidine into the CSF requires alternative forms of chemotherapy, such as melarsoprol in combination with suramin. In treating Onchocerca volvulus infections, suramin kills adult worms and is an alternative to ivermectin. Suramin is used after initial treatment with diethylcarbamazine, which is used to kill the microfilariae. It produces favorable results in pemphigus and prolongs the time to disease progression in hormone-refractory prostate cancer. 

Porterfield, H. UsToo PC-SPES surveys review of studies and update of previous survey results. Mol Urol 2000 4(3) 289-291. de la Taille, A., O. R. Hayek, M. Burchardt, T. Burchardt, and A. E. Katz. Role of herbal compounds (PC-SPES) in hormone-refractory prostate cancer two case reports. J Altern Complement Med 2000 6(5) 449-451. 

Small EJ, Sacks N, Neumanitis J, Urba WJ, et al. 2007. Granulocyte macrophage colony-stimulating factor-secreting allogeneic cellular immunotherapy for hormone-refractory prostate cancer. Clin Cancer Res. 13 3883-3891. 

Chang SS, Benson MC, Campbell SC, Crook J, Dreicer R, Evans CP, Hall MC, Higano C, Kelly WK, Sartor O, Smith Jr JA. Society of Urologic Oncology position statement. Redefining the management of hormone-refractory prostate carcinoma. Cancer 2005 103 11-21. 

Takezawa Y, Nakata S, Kobayashi M, Kosaku N, Fukabori Y, Yamanaka H. Moderate dose diethylstilbestrol diphosphate therapy in hormone refractory prostate cancer. Scand J Urol Nephrol 2001 35(4) 283-7. 

Michinaga S, Ariyoshi A. High-dose intravenous diethylstilbestrol diphosphate therapy for hormone-refractory prostate cancer. Nishinihon J Urol 2002 64 203-5. 

Deeb DD, Jiang H, Gao X, Divine G, Dulchavsky SA, Gautam SC. 2005. Chemo-sensitization of hormone-refractory prostate cancer cells by curcumin to TRAIL-induced apoptosis. J Exp Ther Oncol 5 81-91. 

Dorai T, Dutcher JP, Dempster DW, Wiernik PH. 2004. Therapeutic potential of curcumin in prostate cancer-V Interference with the osteomimetic properties of hormone refractory C4-2B prostate cancer cells. Prostate 60 1-17. 

Ryan CJ, Lin AM, Small EJ. Angiogenesis inhibition plus chemotherapy for metastatic hormone refractory prostate cancer history and rationale. Urol Oncol. 2006 24 250-253. 

Unfortunately, nearly all patients with advanced prostate cancer eventually become refractory to hormone therapy. A regimen of mitoxantrone and prednisone is approved in patients with hormone-... 

M. Hussain. 2000. Phase II study of dolas-tatin-10 in patients with hormone-refractory metastatic prostate adenocarcinoma. Clin. Cancer Res. 6 4205-4208. 

Noguchi, M., Itoh, K., Suekane, S., et al. (2004) Phase I trial of patient-oriented vaccination in HLA-A2-positive patients with metastatic hormone-refractory prostate cancer. Cancer Sci. 95(1), 77-84. 

JM216 (B MS 182751) has been evaluated in small-cell lung cancer [45], non-small-cell lung cancer (NSCLC) [46] [47], hormone refractory prostate cancer [48] and ovarian cancer (unpublished), all using the daily x 5 schedule. JM216 exhibited antitumor activity in patients presenting with previously untreated small-cell lung cancer [45]. Responses included 5 partial responses and 5 stable disease, and overall was 5/16 (31%). 

Sipuleucel-T, Dendreon (BLA-STN 125197) Indicated for the Treatment of Men with Asymptomatic Metatatic Hormone Refractory Prostate Cancer. Cellular, Tissue and Gene Therapies Advisory Committee Meeting March 29, 2007. http // www.fda.gov/ohrms/dockets/ac/cber07.htm CellularTissueGeneTherapies... 

A prostate secretory protein PSP94 has been reported to suppress prostate cancer growth in a mouse disease model (Procoyn Biopharma, London, Ont.). The results suggest that protein induces cell death specifically in cancer cells refractory to human hormones. 

Mutations have been found in primary untreated, local and metastatic hormone-refractory prostate cancer as well as in LNCaP cells. However, mutations seem to be more common in advanced and hormone-refractory prostate cancers (C25, E5, L4, N3, S30, S31, Tl, T5). This point is still debated. Transition mutations, where a purine is replaced by a purine or a pyrimidine by a another pyrimidine, seems to be more common in prostate cancer than transversion mutations, where a purine is converted to a pyrimidine or vice versa. It was proposed that this may be due to endogenous carcinogens (HI). 

Several cytokine receptors are present in prostate tumors and in prostate cancer cell lines. These include the granulocyte-macrophage colony-stimulating factor receptors (GM-CSF-R) and macrophage colony-stimulating factor receptor (M-CSF-R) (R7, RIO, S4). The presence of interleukin receptors in the prostate tumor which bind interleukins such as IL-2, IL-3, and IL-6 may play a role in hormone-dependent as well as in hormone-refractory prostate cancer tumors (Cl3, R6). However, the importance of these receptors needs to be illuminated. 

Kll. Koivisto, P. A., and Rantala, I., Amplification of the androgen receptor gene is associated with P53 mutation in hormone-refractory recurrent prostate cancer. J. Pathol. 187, 237-241 (1999). 

Scher, H. I., and Kelly, W. K., Flutamide withdrawal syndrome Its impact on clinical trials in hormone-refractory prostate cancer. J. Clin. Oncol. 11, 1566-1572 (1993). 

Benzofurotriazoles 353 were prepared and their activity in the inhibition of CYP26A1 evaluated in a MCF-7 cell assay. These compounds are analogues of the advanced pharmaceutical candidate liarozole, 354 <2006MIP308-86>. CYP26A1 catalyzes the metabolism of all-/ra j retenoic acid (ATRA) and is believed to be principally responsible for controlling the levels of this retenoid. Elevated levels of ATRA are used to treat hormone refractory prostate cancer and psoriasis. It is hoped that inhibition of CYP26A1 will limit the development of resistance to these retinoid treatments. 

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