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Androgen Ablation (androgen + ablation)
Terms modified by Androgen Ablation Selected AbstractsRegulation of global gene expression in the bone marrow microenvironment by androgen: Androgen ablation increases insulin-like growth factor binding protein-5 expressionTHE PROSTATE, Issue 15 2007Chang Xu Abstract BACKGROUND Prostate cancer frequently metastasizes to bone. Androgen suppression treatment is initially highly effective, but eventually results in resistant cancer cells. This study evaluates the effects of androgen suppression on the bone and bone marrow (BM). In particular we questioned whether the androgen therapy could adversely facilitate prostate cancer progression through an increase growth factor secretion by the bone microenvironment. METHODS Global gene expression is analyzed on mPEDB DNA microarrays. Insulin-like growth factor binding protein-5 (IGFBP5) is detected by immunohistochemistry in mouse tissues and its regulation measured by qPCR and Western blotting in human BM stromal cells. Effects of extracellular matrix-associated IGFBP5 on human prostate epithelial cells are tested in an MTS cell-growth assay. RESULTS Castration increases expression of 159 genes (including 4 secreted cytokines) and suppresses expression of 84 genes. IGFBP5 is most consistently increased and the increase in expression is reversed by testosterone administration. IGFBP5 protein is detected in vivo in osteoblasts, BM stromal cells, and endothelial cells. Primary human stromal cell cultures secrete IGFBP5. In vitro, treatment of immortalized human marrow stromal cells with charcoal-stripped serum increases IGFBP5 mRNA expression, which is reversed by androgen supplementation. IGFBP5 is incorporated into the extracellular matrix. Further, IGFBP5 immobilized on extracellular matrices of stromal cells enhances the growth of immortalized prostate epithelial cells. CONCLUSIONS Androgen suppressive therapy increases IGFBP5 in the BM microenvironment and thereby may facilitate the progression of prostate cancer. Prostate 67: 1621,1629, 2007. © 2007 Wiley-Liss, Inc. [source] Flutamide reduced prostate cancer development and prostate stem cell antigen mRNA expression in high grade prostatic intraepithelial neoplasiaINTERNATIONAL JOURNAL OF CANCER, Issue 4 2008Zhao Zhigang Abstract High-grade prostatic intraepithelial neoplasia (HGPIN) appears to represent an ideal target for chemoprevention of prostate cancer (PCa). HGPIN responds to androgen ablation and has prostate stem cell antigen (PSCA) mRNA expression. One hundred and seventy two patients with isolated HGPIN were randomized in a double-blind manner to receive flutamide 250 mg/day (86 cases) or a placebo (86 cases) for 12 months and were rebiopsied at 12 and 60 months. PSCA mRNA expression was assessed in the prestudy and 12-month biopsies by in situ hybridization. The incidence of subsequent PCa was 11.6% in the flutamide group when compared with 30.2% in the placebo group over a follow-up period of 5 years (p = 0.0027). PSCA mRNA expression levels were significantly declined after treatment compared with that before treatment (p < 0.001). After treatment, 66 patients had reduced PSCA mRNA expression, in whom none was found with cancer on follow-up, however, 13 cases had increased PSCA mRNA expression levels, in whom 11 were found with cancer. Cox regression analysis demonstrated that HGPIN with increased PSCA mRNA expression after flutamide had an increased relative risk of 4.33 to develop subsequent cancer (95% confidence intervals: 2.48,7.36; p < 0.001). Seventeen (19.8%) cases had the flutamide-associated side effects, which were graded as mild, but all did not discontinue study. Flutamide can effectively and safely reduce PCa development and significantly suppress PSCA mRNA expression in men with isolated HGPIN, whereas the increased PSCA mRNA expression after therapy may be a clinically adverse predictor for cancer onset. © 2007 Wiley-Liss, Inc. [source] Original Article: Clinical Investigation: Neuroendocrine differentiation in stage D2 prostate cancersINTERNATIONAL JOURNAL OF UROLOGY, Issue 5 2008Naoto Kamiya Objectives: Chromogranin A (CgA) and neuro-specific enolase (NSE) are gaining acceptance as markers of several types of neuroendocrine tumors and the concentration of CgA and NSE have been reported to be elevated in relation to neuroendocrine differentiation of prostate cancer. The aim of the present study was to examine the correlation between the immunohistochemical (IHC) findings and serum value for CgA and NSE in untreated stage D2 prostate cancer patients. Methods: Immunohistochemistry was carried out using antibodies against CgA and NSE in 58 patients and, pretreatment serum CgA and NSE levels were measured by monoclonal immunoradiometric assay in 18 patients with stage D2 prostate cancer treated by androgen ablation. We examined the relationship of the pretreatment serum level to IHC findings for CgA and NSE in prostate cancer patients to clinicopathological parameters, and prognosis. Also, we evaluated the correlation of IHC findings to serum levels for CgA and NSE. Results: There was a statistically significant correlation between CgA positivity and serum CgA level (P = 0.0421). However, there was no statistically significant correlation between NSE positivity and serum NSE level (P > 0.05). We divided stage D2 patients into three groups according to IHC positivity of CgA and NSE. The cause-specific survival was significantly poorer in patients with strongly positive (++) patients for independent CgA and combined CgA with NSE (P = 0.0379). Multivariate analysis of cause-specific survivals in patients with stage D2 prostate cancer demonstrated that strong IHC stain was considered as independent variable associated with greater risk of death (P = 0.0142). Conclusion: Neuroendocrine differentiation in stage D2 prostate cancer has attracted considerable attention as a potentially findings prognosis. Thus, CgA had a stronger relationship between serum levels and IHC positivity in contrast to NSE, suggesting clinical usefulness as a tumor marker in predicting the extent of neuroendocrine differentiation in prostate cancer. [source] Importance of C16 ceramide accumulation during apoptosis in prostate cancer cellsINTERNATIONAL JOURNAL OF UROLOGY, Issue 2 2006MASATOSHI ETO Aim:, Adenocarcinoma of the prostate is one of the most frequently diagnosed non-cutaneous cancers and the second leading cause of cancer-related deaths among men in the United States. To fully understand the role of ceramide during apoptosis induced by androgen ablation, we modified the levels of intracellular ceramide by pharmacological agents as well as through serum deprivation in androgen-dependent and independent cell lines. Methods:, Ceramide levels were modified using N-oleoylethanolamine (NOE), sphingosine-1-phosphate (S1P) as well as through serum deprivation, in LNCaP, DU145 and PC-3 prostate cancer cells. Various methods including nonyl acridine orange staining, propidium iodide staining/cell cycle analysis and lipid analysis were utilized. Results:, Our results demonstrate that the inhibition of acid ceramidase by NOE enhances the intracellular ceramide levels induced by androgen ablation in androgen-dependent LNCaP cells, and is accompanied by an increase in apoptotic cells. Sphingosine 1-phosphate had no effect in rescuing LNCaP cells from apoptosis induced by androgen ablation. Our results also show that serum deprivation causes intracellular ceramide accumulation and apoptosis in androgen-independent prostate cancer cells. Conclusions:, Our studies indicate that the increase in intracellular ceramide itself, but not the balance between ceramide and S1P, determines whether LNCaP cells undergo apoptosis. Our results also show that the increase in intracellular ceramide strongly correlates with apoptosis induced by serum deprivation even in androgen-independent prostate cancer cell lines. [source] Antisense oligodeoxynucleotide therapy targeting clusterin gene for prostate cancer: Vancouver experience from discovery to clinicINTERNATIONAL JOURNAL OF UROLOGY, Issue 9 2005HIDEAKI MIYAKE Abstract Background The objective of this study was to review our experience in the development of antisense (AS) oligodeoxynucleotide (ODN) therapy for prostate cancer targeting antiapoptotic gene, clusterin. Methods We initially summarized our data demonstrating that clusterin could be an optimal therapeutic target for prostate cancer, then presented the process of developing AS ODN therapy using several preclinical animal models. Finally, the preliminary data of the recently completed phase I clinical trial using AS clusterin ODN as well as the future prospects of this therapy are discussed. Results Expression of clusterin was highly up-regulated after androgen withdrawal and during progression to androgen-independence, but low or absent in untreated tissues in both prostate cancer animal model systems and human clinical specimens. Introduction of the clusterin gene into human prostate cancer cells confers resistance to several therapeutic stimuli, including androgen ablation, chemotherapy and radiation. AS ODN targeting the translation initiation site of the clusterin gene markedly inhibited clusterin expression in prostate cancer cells in a dose-dependent and sequence-specific manner. Systemic treatment with AS clusterin ODN enhanced the effects of several conventional therapies through the effective induction of apoptosis in prostate cancer xenograft models. Based on these findings, a phase I clinical trial was completed using AS clusterin ODN incorporating 2,-O-(2-methoxy)ethyl-gapmer backbone (OGX-011), showing up to 90% suppression of clusterin in prostate cancer. Conclusions The data described above identified clusterin as an antiapoptotic gene up-regulated in an adaptive cell survival manner following various cell death triggers that helps confer a phenotype resistant to therapeutic stimuli. Inhibition of clusterin expression using AS ODN technology enhances apoptosis induced by several conventional treatments, resulting in the delay of AI progression and improved survival. Clinical trials using AS ODN confirm potent suppression of clusterin expression and phase II studies will begin in early 2005. [source] Molecular regulation of androgen action in prostate cancer,JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2006Scott M. Dehm Abstract Androgens are critical regulators of prostate differentiation and function, as well as prostate cancer growth and survival. Therefore, androgen ablation is the preferred systemic treatment for disseminated prostate cancer. Androgen action is exerted in target tissues via binding the androgen receptor (AR), a nuclear receptor transcription factor. Historically, the gene expression program mediated by the AR has been poorly understood. However, recent gene expression profiling and more traditional single-gene characterization studies have revealed many androgen-regulated genes that are important mediators of androgen action in both normal and malignant prostate tissue. This review will focus on the androgen-regulated gene expression program, and examine how recently identified androgen-regulated genes are likely to contribute to the development and progression of prostate cancer. We will also summarize several recent studies that have attempted to unravel how these genes are deregulated in androgen depletion independent prostate cancer. J. Cell. Biochem. 99: 333,344, 2006. © 2006 Wiley-Liss, Inc. [source] ORIGINAL ARTICLE: Identification of Toll-Like Receptors in the Rat (Rattus norvegicus): Messenger RNA Expression in the Male Reproductive Tract Under Conditions of Androgen VariationAMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 4 2009Barnali Biswas Problem, Although the majority of Toll-like receptors (TLRs) are reported in many species, some of them are not yet described in the rat. Further, factors that govern Tlr expression in the male reproductive tract have received little attention. We attempt to identify and characterize Tlrs in the rat and determine the expression profile under conditions that affect male reproductive tract gene expression. Method of study, Rat Tlr5, Tlr10, and Tlr11 transcript sequences were submitted to GenBank and in silico characterization carried out using bioinformatics tools. RT-PCR analyses using gene specific primers for rat Tlr1,13 were carried out with RNA isolated from reproductive tract tissues of various experimental groups. Results,Tlr5, Tlr10, and Tlr11 identified in this study share features that are characteristic of the known TLRs. Abundant Tlr expression was observed in the male reproductive tract of adult and developing rats. Further, Tlr expression was also observed in the epididymides of androgen ablated rats. Conclusion,Tlr5, Tlr10, and Tlr11 are ubiquitously expressed in the rat. Tlrs seem to be expressed during male reproductive tract development and under conditions of androgen ablation, suggesting the preparedness of the male reproductive tract to detect an infection under all conditions of androgen status. [source] Nuclear androgen receptors recur in the epithelial and stromal compartments of malignant and non-malignant human prostate tissue several months after castration therapyTHE PROSTATE, Issue 12 2007Pernilla Wikström Abstract BACKGROUND As changed paracrine support from androgen receptor (AR)-positive cells in the prostate stroma contribute to castration-induced glandular involution, we examined if the subsequent relapse to androgen-independent epithelial cell growth could be related to reactivation of AR signaling in the stroma. MATERIALS AND METHODS Human prostate tissue taken before, within 14 days, and at suspected local tumor relapse after surgical castration therapy was immunostained for AR. RESULTS Castration initially decreased nuclear AR staining in epithelial and stroma cells, in both tumor and non-malignant tissue, but after some months, it reappeared. CONCLUSIONS Local tumor relapse was associated with reappearance of nuclear AR not only in tumor epithelial cells but also in the tumor stroma. Reappearance of nuclear AR in non-malignant prostate cells may be a physiological response to long-term systemic androgen ablation that could influence tumor growth. Prostate 67: 1277,1284, 2007. © 2007 Wiley-Liss, Inc. [source] Relaxin becomes upregulated during prostate cancer progression to androgen independence and is negatively regulated by androgensTHE PROSTATE, Issue 16 2006Vanessa C. Thompson Abstract BACKGROUND Relaxin is a potent peptide hormone normally secreted by the prostate. This study characterized relaxin expression during prostate cancer progression to androgen independence (AI), and in response to androgens. METHODS The prostate cancer cell line, LNCaP, was assayed by microarrays and confirmatory Northern analysis to assess changes in relaxin levels due to androgen treatment and in LNCaP xenografts following castration. Relaxin protein levels were examined by immunohistochemistry (IHC) in tissue microarrays of human prostate cancer samples following androgen ablation. RESULTS Relaxin levels decreased in a time and concentration-dependent manner due to androgens in vitro, and increased in xenografts post-castration. Relaxin increased in radical prostatectomy specimens after 6 months of androgen ablation and in AI tumors, was highest in bone metastases. CONCLUSIONS Relaxin is negatively regulated by androgens in vitro and in vivo, which correlates to clinical prostate cancer specimens following androgen ablation. The role of relaxin in angiogenesis and tissue remodeling suggests it may contribute to prostate cancer progression. Prostate © 2006 Wiley-Liss, Inc. [source] YB-1 is upregulated during prostate cancer tumor progression and increases P-glycoprotein activityTHE PROSTATE, Issue 3 2004Pepita Giménez-Bonafé Abstract BACKGROUND Currently, the main obstacle to curing advanced prostate cancer is development of androgen independence (AI), where malignant cells acquire the ability to survive in the absence of androgens. Our initial experimental approach used cDNA microarrays to characterize changes in gene expression in the LNCaP human prostate tumor model during progression to AI. The transcription factor Y-box binding protein (YB-1) was shown to be one of the genes upregulated. We focused on increased YB-1 expression during progression in clinical specimens, and further examined one of its downstream targets, P-glycoprotein (P-gp). METHODS Northern blot analysis was performed on LNCaP tumor series, as well as immunohistochemical analyses of human prostate cancer tissue samples. YB-1 was transiently transfected and transport analysis were performed to analyze P-gp efflux activity. RESULTS YB-1 expression is markedly increased during benign to malignant transformation and further following androgen ablation. In addition, increased YB-1 expression after castration in the LNCaP model is linked to upregulation of P-gp. We demonstrate that YB-1 upregulates P-gp activity resulting in a 40% intracellular decrease in the P-gp substrate vinblastine. We have also found that P-gp increases the efflux of the endogenous androgen, dihydrotestosterone (DHT), from prostate cells and leads to decreased androgen regulated gene expression. CONCLUSIONS We hypothesize that early in prostate cancer progression, increased expression of YB-1 may increase P-gp activity which may in turn lower androgen levels in the prostate tumor cells. Suppression of androgen levels may activate cell survival pathways and lead to an adaptive survival advantage of androgen independent prostate cancer cells following androgen ablation therapy. © 2004 Wiley-Liss, Inc. [source] Response of patients with advanced prostatic cancer to administration of somatostatin analog RC-160 (vapreotide) at the time of relapseTHE PROSTATE, Issue 3 2003David González Barcena Abstract BACKGROUND The aim of this study was to evaluate the effects of administration of the somatostatin analog RC-160 (vapreotide) at the time of relapse in patients with androgen independent prostate cancer. METHODS Our study included 13 patients with biopsy-proven prostate cancer, stage D3. Eight patients had been treated with a depot formulation of the agonist D-Trp-6-LH-RH, with a median remission time of 68 (range 48,102 months). Five patients were initially treated by surgical orchiectomy, but relapsed after a median time of 33 months (range 17,91 months). A new remission period with a median duration of 10 months (range 2,29 months) was induced with Ketoconazole in the orchiectomy group. At the relapse time, all the patients received 1 mg of vapreotide t.i.d., by subcutaneous route, in addition to D-Trp-6-LH-RH, or Ketoconazole in the orchiectomy group. RESULTS Eight of 13 patients demonstrated clinical improvement after 3 months of therapy with vapreotide, six showing a decrease in serum prostate specific antigen (PSA) from 234.5,±,308.5 to 68.2,±,60.5 ng/ml (mean decline 71,±,8%; P,<,0.05). Two additional patients presented a fall in serum prostatic acid phosphatase (PAP). Responding patients showed a decrease in the bone pain score from 2.62,±,0.48 to 0.37,±,0.69 and an increase in the Karnofsky performance status from 72.3,±,4.21 to 83.6,±,23.2 (P,<,0.05). In accord with the ECOG criteria, two patients had a complete response; four had partial response, and two had a stable response. Four patients did not respond and one was not evaluable. Two patients died in remission, one at 16 months due to myocardial infarction and the other at 24 months due to pneumonia. Three patients relapsed at 5, 17, and 19 months respectively. Three patients who have been followed-up for more than 3 years continued in remission (79, 45, and 45 months) respectively. Vapreotide was well tolerated, only three patients having transitory mild diarrhea. CONCLUSIONS Our results indicate that therapy with the somatostatin analog vapreotide at the time of relapse can induce objective clinical responses in some patients with prostate cancer who are refractory to androgen ablation induced by LH-RH analogs or orchiectomy. Prostate 56: 183,191, 2003. © 2003 Wiley-Liss, Inc. [source] Possible mechanism of dexamethasone therapy for prostate cancer: Suppression of circulating level of interleukin-6THE PROSTATE, Issue 2 2003Koichiro Akakura Abstract BACKGROUND Glucocorticoids may have favorable effects on prostate cancer patients showing clinical and/or biochemical failure after androgen ablation. The efficacy and mechanisms of dexamethasone therapy as possible alternative endocrine therapy were investigated. METHODS Twenty five patients with prostate cancer treated by androgen ablation and showing a steady increase in serum prostate specific antigen (PSA) were treated with low-dose dexamethasone. RESULTS Of 25 patients, 11 demonstrated 50% or more decline of serum PSA and 9 showed improvement of pain on dexamethasone therapy. Of 8 patients who responded to dexamethasone thearpy, 5 had 80% or more decrease in serum interleukin-6 (IL-6). In contrast, none of 8 non-responders showed remarkable IL-6 suppression. Response of PSA was not correlated to the changes in serum dehydroepiandrosterone, dehydroepiandrosterone sulfate, or androstendione. CONCLUSIONS Significant suppression of serum IL-6, probably through inhibition of androgen-independent activation of androgen receptor, may be one of the mechanisms for the effect of dexamethasone therapy in prostate cancer patients with progressive disease. Prostate 56: 106,109, 2003. © 2003 Wiley-Liss, Inc. [source] Prolonging androgen sensitivity in prostate cancer , a role for COX inhibitors?ANZ JOURNAL OF SURGERY, Issue 9 2009Andrew Richards Abstract Background:, Advanced prostate cancer has long been known to respond to androgen deprivation, but disease inevitably progresses to become androgen independent. Lengthening the responsive period is an important, yet underinvestigated, clinical goal. This study aims to determine whether cyclooxygenase-2 (COX-2) inhibitors are potentially useful agents in prolonging androgen sensitivity. Methods:, The expression of COX-2 in human prostate surgical specimens, both benign and malignant, androgen dependent and independent, was determined by immunohistochemistry. Nude mice, in which prostate cancer xenografts had been established, were castrated and randomized to receive either COX-2 inhibitor or vehicle for 8 weeks. Time to androgen independence (AIPC), growth rate and rate of PSA rise were compared between groups. COX-2 expression, at the mRNA and protein level, was determined in the native xenograft cell line and in tissues of varying androgen sensitivity derived from the xenografts. Results:, In human tissues, COX-2 protein was expressed in prostate epithelium and was upregulated in prostate cancer and remained upregulated after androgen ablation and in the androgen-independent state. Tissue obtained from the LNCaP xenograft model showed variable COX-2 expression, with some evidence of downregulation in AIPC. The addition of a COX-2 inhibitor to castration does not lengthen the time to AIPC (P= 0.53), rate of tumour growth (P= 0.59) or rate of PSA rise (P= 0.34) in the LNCaP xenograft model. Conclusion:, This study does not support a role for COX-2 inhibitors in prolonging androgen responsiveness in prostate cancer. [source] Clinical and socio-demographic profile of an Australian multi-institutional prostate cancer cohortASIA-PACIFIC JOURNAL OF CLINICAL ONCOLOGY, Issue 4 2009Kerri BECKMANN Abstract Aims: To describe the clinical and socio-demographic data from a South Australian prostate cancer cohort (PCCOD). Methods: Clinical data for 2329 prostate cancer patients treated at three South Australian teaching hospitals between 1998 and 2007 were analyzed by place of residence, time of diagnosis and socioeconomic status (SES). ,2 tests were used to investigate differences in stage, grade and prostate-specific antigen (PSA) at diagnosis, among subgroups and over time. Logistic regression was used to examine predictors of treatment modalities. Five-year survival was assessed using Kaplan,Meier methods. Results: The distributions of age, SES and place of residence of PCCOD patients closely reflected those of the state-based prostate cancer population, with rural patients slightly underrepresented. Lower SES or rural residence was not associated with higher stage, grade, PSA level or disease-specific survival. Treatment modalities varied with SES (for radical prostatectomy), rural residence (radical prostatectomy, radiotherapy and androgen ablation), age and clinical characteristics. There was a trend over time towards a younger age at diagnosis and more favorable clinical profiles, consistent with earlier diagnosis. However, the current risk profile for this cohort is similar to that reported approximately a decade earlier in a US series. Conclusion: PCCOD patients have a broadly similar socio-demographic profile to prostate cancer patients statewide. Socioeconomic status is not associated with clinical characteristics at diagnosis, but does predict treatment type. The clinical characteristics of the cohort are consistent with a much later stage presentation than reported in current US case series. [source] Androgen ablation therapy for prostate carcinoma suppresses the immunoreactive telomerase subunit hTERTCANCER, Issue 2 2004Kenneth A. Iczkowski M.D. Abstract BACKGROUND Telomerase is a ribonucleoprotein complex that protects the ends of chromosomes from degradation. Its catalytic subunit, hTERT, controls its activity. Prior data in prostate carcinoma cases indicated that immunohistochemical hTERT reactivity increases with tumor grade and may be absent in lower grade cases. The effect of complete androgen ablation (CAA) on tumor hTERT expression was uncertain. METHODS hTERT immunostaining was performed on the cancerous pretreatment biopsy tissue of 30 men who consecutively underwent CAA with bicalutamide and goserelin acetate for 30 days prior to undergoing radical prostatectomy, and on their tumor tissue from radical prostatectomy. As controls, biopsy and prostatectomy samples from 30 untreated men were studied. Nuclear staining was evaluated by two observers, and the change in staining between biopsy and prostatectomy samples was evaluated using the Student t test in both groups. RESULTS The percent of reactive tumor nuclei in treated men declined from 36.7% to 13.2% (P = 0.0001), and declined from 19.8% to 16.1% in untreated men (P = 0.4). The greater mean hTERT reactivity in the treated men's biopsy specimens was attributed to an increased proportion of higher (Gleason score , 7) grade tumors. The decline in hTERT immunostaining remained significant after normalizing it to that of the untreated group (P = 0.002). The original Gleason scores, corresponding declines in the percentage of reactive tumor nuclei, and significance were: Gleason score , 6: 11% (P = 0.03); Gleason score of 7: 23% (P < 0.006); and Gleason score , 8: 46% (P < 0.005) (from a mean 63% to 17%). CONCLUSIONS CAA for prostate carcinoma can be considered an antitelomerase therapy. The steepest reduction in telomerase activity was noted in the highest grade tumors. Cancer 2004;100:294,9. © 2003 American Cancer Society. [source] Rapid rise of serum prostate specific antigen levels after discontinuation of the herbal therapy PC-SPES in patients with advanced prostate carcinomaCANCER, Issue 3 2002Report of four cases Abstract BACKGROUND PC-SPES is an herbal supplement whose mechanisms of action are poorly understood, but may be estrogenic. The objective of the current report is to describe the effects of discontinuing PC-SPES treatment in four patients with androgen-independent prostate carcinoma. METHODS Patient charts were retrospectively reviewed. A MEDLINE search was performed to investigate whether these effects of PC-SPES had been previously reported. RESULTS Four men whose metastatic prostate carcinoma progressed despite androgen ablation and subsequent PC-SPES treatment are described. All four patients developed a rapid increase in serum prostate specific antigen (PSA) within one month of stopping PC-SPES, ranging from 345% to 880%. Two patients increased their PSA levels to 1300% and 1400% after 7 weeks. Compared to the rate of rise of PSA levels prior to and during PC-SPES therapy, the rise after stopping this treatment was much higher than expected. Clinical symptoms remained relatively stable despite the serologic changes. CONCLUSIONS Discontinuing PC-SPES therapy can be associated with a rapid rise in PSA. To the authors' knowledge, this effect has not been reported previously. This effect should be considered in the design of clinical trials as well as in the standard management of androgen-independent prostate carcinoma patients. Cancer 2002;94:686,9. © 2002 American Cancer Society. DOI 10.1002/cncr.10269 [source] | ||||||||||||||||||||||