National Cancer Institute®
Last Modified: April 1, 2002
UI - 11569230
AU - Kariakin OB; Sviridova TV; Tsodikova LB; Grishin GN; Sergeeva TN;
TI - Perekhrest MA; Donichkina EA [Changes in prostate-specific antigen in casodex (bicalutamide) monotherapy in a dose 150 mg/day given to patients with locally advanced and/or advanced prostatic cancer]
SO - Urologiia 2001 Jul-Aug;(4):26-9
Three-month treatment with casodex (150 mg/day) of untreated patients with locally advanced and/or advanced cancer of the prostate is well tolerated. The only side effect encountered in 9(60%) patients was temporary breast painfulness and swelling. Subjective effects consisted of higher activity (in 40% of patients), pain relief (in 33.3%), improved urination (in 80%). Objective effects comprise: reduction of prostate-specific antigen in 14(93.3%) patients by 150.4 ng/ml at the average; a rise in testosterone concentration in 12(80%) patients; regression of the tumor by more than 50% in 5(33.3%) patients; stabilization and partial regression of regional metastases (1 case); stabilization of distant metastases (3 of 4 cases). One patient showed progression of bone metastasizing in partial local regression of the tumor.
UI - 11569231
AU - Medvedev VL
TI - [Hormone-resistant epithelial cancer of the prostate]
SO - Urologiia 2001 Jul-Aug;(4):29-33
The study of the prognostic criteria of hormone-resistant prostatic cancer (PC) by specifying expression of androgen receptor protein as well as Bcl-2 and p53 proteins, apoptosis regulators, has demonstrated that tumor cells of hormone-sensitive and hormone-resistant PC forms have different variants of immunophenotype. Hormone-resistance is typical for tumors from urothelial, basal and neuroendocrine PC cells, glandular epithelium cells which lost androgen receptors (AR) and tumors consisting of cells which retain AR but simultaneously express Bcl-2 and/or p53 genes. The discovery of androgen-resistant cancer from glandular epithelium which has immunophenotype characteristics of a hormone-dependent tumor indicates the existence of other mechanisms of protection against apoptosis. The development of hormone-resistant cancer 2.5-3 years after hormonal therapy is associated with changes in immunophenotype of tumor cells. They become Bcl-2- and/or p53-positive while part of them lose AR. Thus, immunophenotype of tumor cells may serve a prognostic marker of hormonal resistance of the tumor and dictate the treatment policy.
UI - 11875726
AU - Parker CC; Norman AR; Huddart RA; Horwich A; Dearnaley DP
TI - Pre-treatment nomogram for biochemical control after neoadjuvant androgen deprivation and radical radiotherapy for clinically localised prostate cancer.
SO - Br J Cancer 2002 Mar 4;86(5):686-91
AD - Academic Department of Radiotherapy and Oncology, The Royal Marsden NHS Trust and Institute of Cancer Research, Downs Road, Sutton, Surrey SM2 5PT, UK. email@example.com
Phase III studies have demonstrated the clinical benefit of adding neo-adjuvant androgen deprivation to radical radiotherapy for clinically localised prostate cancer. We have developed a nomogram to describe the probability of PSA control for patients treated in this way. Five hundred and seventeen men with clinically localised prostate cancer were treated with 3-6 months of neo-adjuvant androgen deprivation and radical radiotherapy (64Gy in 32#) between 1988 and 1998. Median presenting PSA was 20 ng x ml(-1), and 56% of patients had T3/4 disease. Multivariate analysis of pre-treatment factors was performed, and a nomogram developed to describe PSA-failure-free survival probability. At a median follow-up of 44 months, 233 men had developed PSA failure. Presenting PSA, histological grade and clinical T stage were all highly predictive of PSA failure on multivariate analysis. The nomogram score for an individual patient is given by the summation of PSA (<10=0, 10-19=16, 20-49=44, > or =50=100), grade (Gleason 2-4=0, 5-7=44, 8-10=81) and T stage (T1/2=0, T3/4=35). For a nomogram score of 0, 50, 100 and 150 points the 2 year PSA control rate was 93, 87, 75 and 54%, and the 5 year PSA control rate was 82, 67, 44 and 18%. These results are comparable to those using surgery or higher doses of radical radiotherapy alone. The nomogram illustrates the results of multivariate analysis in a visually-striking way, and facilitates comparisons with other treatment methods. Copyright 2002 Cancer Research UK
UI - 11896607
AU - Dhanalakshmi S; Singh RP; Agarwal C; Agarwal R
TI - Silibinin inhibits constitutive and TNFalpha-induced activation of NF-kappaB and sensitizes human prostate carcinoma DU145 cells to TNFalpha-induced apoptosis.
SO - Oncogene 2002 Mar 7;21(11):1759-67
AD - Department of Pharmaceutical Sciences, School of Pharmacy, University of Colorado Health Sciences Center, Denver, Colorado, CO 80262, USA.
Prostate cancer (PCA) is one of the most common invasive malignancies of men in the US, however, there have been limited successes so far in its therapy. Even most potent agents (e.g. TNFalpha) are ineffective in killing human PCA cells possibly due to constitutive activation of NF-kappaB that subsequently activates a large number of anti-apoptotic genes. In such a scenario, strong apoptotic agent TNFalpha, further induces NF-kappaB activation rather than inducing apoptosis. In several recent studies, we have demonstrated both cancer preventive and anti-cancer efficacy of silymarin and its constituent silibinin in a variety of experimental tumor models and cell culture systems. Here we examined whether silibinin is effective in inhibiting constitutive NF-kappaB activation in human PCA cells, which would help in overcoming TNFalpha-insensitivity. Our studies reveal that silibinin effectively inhibits constitutive activation of NF-kappaB in advanced human prostate carcinoma DU145 cells. Consistent with this, nuclear levels of p65 and p50 sub-units of NF-kappaB were also reduced. In the studies assessing molecular mechanism of this effect, silibinin treatment resulted in a significant increase in the level of IkappaBalpha with a concomitant decrease in phospho-IkappaBalpha. Kinase assays revealed that silibinin dose-dependently decreases IKKalpha kinase activity. The effect of silibinin on IKKalpha seemed to be direct as evidenced by the in vitro kinase assay, where immunoprecipitated IKKalpha was incubated with silibinin. This shows that silibinin does not necessarily need an upstream event to bring about its inhibitory effect on IKKalpha and downstream effectors. Additional studies showed that silibinin also inhibits TNFalpha-induced activation of NF-kappaB via IkappaBalpha pathway and subsequently sensitizes DU145 cells to TNFalpha-induced apoptosis. These results indicate that silibinin could be used to enhance the effectiveness of TNFalpha-based chemotherapy in advanced PCA.
UI - 11760560
AU - Carducci MA; NCCN Prostate Cancer practice Guidelines Panel
TI - NCCN: New chemotherapeutic approaches to hormone refractory prostate cancer.
SO - Cancer Control 2001 Nov-Dec;8(6 Suppl 2):62-5
UI - 11900223
AU - Salido M; Vilches J; Lopez A; Roomans GM
TI - Neuropeptides bombesin and calcitonin inhibit apoptosis-related elemental changes in prostate carcinoma cell lines.
SO - Cancer 2002 Jan 15;94(2):368-77
AD - Department of Medical Cell Biology, University of Uppsala, Sweden. firstname.lastname@example.org
BACKGROUND: Etoposide-induced apoptosis in prostate carcinoma cells is associated with changes in the elemental content of the cells. The authors previously reported that calcitonin and bombesin inhibited etoposide-induced apoptosis in these cells. In the current study, the authors investigated whether these neuropeptides block the etoposide-induced changes in elemental content. METHODS: Cells from the PC-3 and Du 145 prostate carcinoma cell lines were grown either on solid substrates or on thin plastic films on titanium electron microscopy grids, and they were exposed to etoposide for 48 hours in the absence or presence of calcitonin and bombesin. After the exposure, the cells were frozen and freeze dried, and their elemental content was analyzed by energy-dispersive X-ray microanalysis in both in the scanning electron microscope and the scanning transmission electron microscope. RESULTS: Etoposide treatment consistently induced an increase in the cellular Na concentration and a decrease in the cellular K concentration, resulting in a marked increase of the Na/K ratio and also an increase in the phosphorus:sulphur (P/S) ratio. Both bombesin and calcitonin inhibited the etoposide-induced changes in the cellular Na/K ratio, and calcitonin, but not bombesin, inhibited the changes in the P/S ratio. No significant elemental changes were found with bombesin or calcitonin alone. CONCLUSIONS: The neuropeptides bombesin and calcitonin, which inhibited etoposide-induced apoptosis, also inhibited the etoposide-induced elemental changes in prostate carcinoma cells. This important fact strengthens the link between apoptosis and changes in the intracellular elemental content. This correlation provides an objective basis for the study of neuropeptide target points and may be helpful for alternative therapeutic protocols using neuropeptide inhibitors in the treatment of patients with advanced prostatic carcinoma.
UI - 11904315
AU - Potosky AL; Reeve BB; Clegg LX; Hoffman RM; Stephenson RA; Albertsen PC;
TI - Gilliland FD; Stanford JL Quality of life following localized prostate cancer treated initially with androgen deprivation therapy or no therapy.
SO - J Natl Cancer Inst 2002 Mar 20;94(6):430-7
AD - Division of Cancer Control and Population Sciences, National Cancer Institute, Bethesda, MD.
BACKGROUND: Many men diagnosed with clinically localized prostate cancer are initially treated conservatively, receiving neither surgery nor radiotherapy for the first year. Treatment patterns and quality-of-life outcomes have not been previously reported for a population-based sample of such men. METHODS: A population-based random sample of men (n = 661) from six geographic regions who had been newly diagnosed with clinically localized prostate cancer from 1994 through 1995 were followed for up to 1 year. Eligible subjects received neither surgery nor radiotherapy within 1 year of initial diagnosis. We assessed disease-specific and generic quality-of-life outcomes in men receiving androgen deprivation therapy (ADT) compared with men receiving no therapy. All statistical tests were two-sided. RESULTS: Two hundred and forty-five study patients received ADT and the remaining 416 patients received no therapy. Approximately two thirds of the patients (n = 159) receiving ADT had either baseline Gleason scores greater than six or serum prostate-specific antigen values above 20 ng/mL. Among men who were sexually potent before diagnosis (ADT = 88 patients; no therapy = 223 patients), 80% of those on ADT reported being impotent after 1 year compared with 30% of those receiving no treatment (P < .001). Patients receiving ADT reported more physical discomfort 1 year after diagnosis than did men who had received no therapy. However, patients receiving ADT, compared with those receiving no therapy, were more likely to be satisfied with their treatment decision (56% pleased versus 45.3%; P =.001). Patients on ADT also experienced a statistically significant decline in vitality, but not in physical function, after adjustment for the confounding factors (P =.05). CONCLUSION: ADT is a commonly used primary therapy for clinically localized prostate cancer. Therefore, men considering ADT as an initial treatment should be aware that sexual function and some aspects of physical well-being are likely to be affected in the first year following this treatment.
UI - 11893639
AU - Nutting CM; Corbishley CM; Sanchez-Nieto B; Cosgrove VP; Webb S;
TI - Dearnaley DP Potential improvements in the therapeutic ratio of prostate cancer irradiation: dose escalation of pathologically identified tumour nodules using intensity modulated radiotherapy.
SO - Br J Radiol 2002 Feb;75(890):151-61
AD - Department of Radiotherapy, Institute of Cancer Research and Royal Marsden NHS Trust, Sutton, SM2 5PT, UK.
The potential of intensity modulated radiotherapy (IMRT) to improve the therapeutic ratio in prostate cancer by dose escalation of intraprostatic tumour nodules (IPTNs) was investigated using a simultaneous integrated boost technique. The prostate and organs-at-risk were outlined on CT images from six prostate cancer patients. Positions of IPTNs were transferred onto the CT images from prostate maps derived from sequential large block sections of whole prostatectomy specimens. Inverse planned IMRT dose distributions were created to irradiate the prostate to 70 Gy and all the IPTNs to 90 Gy. A second plan was produced to escalate only the dominant IPTN (DIPTN) to 90 Gy, mimicking current imaging techniques. These plans were compared with homogeneous prostate irradiation to 70 Gy using dose-volume histograms, tumour control probability (TCP) and normal tissue complication probability (NTCP) for the rectum. The mean dose to IPTNs was increased from 69.8 Gy to 89.1 Gy if all the IPTNs were dose escalated (p=0.0003). This corresponded to a mean increase in TCP of 8.7-31.2% depending on the alpha/beta ratio of prostate cancer (p<0.001), and a mean increase in rectal NTCP of 3.0% (p<0.001). If only the DIPTN was dose escalated, the TCP was increased by 6.4-27.5% (p<0.003) and the rectal NTCP was increased by 1.8% (p<0.01). In the dose escalated DIPTN IMRT plans, the highest rectal NTCP was seen in patients with IPTNs in the posterior peripheral zone close to the anterior rectal wall, and the lowest NTCP was seen with IPTNs in the lateral peripheral zone. The ratio of increased TCP to NTCP may represent an improvement in the therapeutic ratio, but was dependent on the position of the IPTN relative to the anterior rectal wall. Improvements in prostate imaging and prostate immobilization are required before clinical implementation would be possible. Clinical trials are required to confirm the clinical benefits of these improved dose distributions.
UI - 11771565
AU - Anonymous
TI - Results of 12-year study show brachytherapy is as effective as surgery.
SO - Rep Med Guidel Outcomes Res 2000 Jul 20;11(15):10, 12
UI - 11901478
AU - Cooper CR; Chay CH; Pienta KJ
TI - New discoveries in prostate cancer biology and treatment. 5-9 December 2001, Naples, Florida, USA.
SO - Expert Opin Ther Targets 2002 Feb;6(1):123-7
AD - University of Michigan Comprehensive Cancer Center, Department of Internal Medicine, Division of Haematology/Oncology and Department of Urology, Ann Arbor, MI 48109, USA.
Androgen independence and bone metastasis are lethal complications in patients with advanced prostate cancer. Presently, there is no cure for patients with androgen-independent prostate cancer. In order to develop more effective therapies for this disease, the molecular events involved in the development of androgen independence and bone metastasis must be elucidated and then targeted by therapeutic agents. Several studies presented at a recent conference on prostate cancer sponsored by the American Association for Cancer Research (AACR) provided evidence that prostate cancer metastasis to bone is mediated by the prostate cancer cell expression of molecules that allow the cells to invade, grow in and stimulate cells in the bone microenvironment resulting in an osteoblastic reaction. Androgen independence was reportedly mediated by an increased expression of survival genes following androgen ablation therapies and several molecular mechanisms involved in genetic instability. Treatment strategies are being designed to target some of the molecular events involved in androgen independence and bone metastasis. Targeting these molecular events with combinational therapies will hopefully delay the progression to androgen independence in patients with early stage disease, suppress the growth of androgen-independent cells in patients with advanced disease and enhance the chemosensitivity of androgen-independent cells.
UI - 11920525
AU - Akerley W; Butera J; Wehbe T; Noto R; Stein B; Safran H; Cummings F;
TI - Sambandam S; Maynard J; Di Rienzo G; Leone L A multiinstitutional, concurrent chemoradiation trial of strontium-89, estramustine, and vinblastine for hormone refractory prostate carcinoma involving bone.
SO - Cancer 2002 Mar 15;94(6):1654-60
AD - Boston University Medical Center, Oncology-Hematology, Boston, Massachusetts 02118, USA. Wallace.Arkerley@bmc.org
BACKGROUND: Estramustine phosphate (EMP) and vinblastine have radiosensitizing properties and significant activity against hormone refractory prostate carcinoma. Strontium-89 is a palliative agent that acts as a selective radiation source for bone metastasis. The combination of EMP, vinblastine, and strontium-89 was developed to exploit the potential for radiosynergy. PATIENTS AND METHODS Forty-four patients at the Brown Oncology Group affiliated hospitals were treated with oral EMP 600 mg/m2 daily on Weeks 1-4 and 7-10, vinblastine 4 mg/m2 intravenously once each week on Weeks 1-4 and 7-10, and strontium-89 2.2 MBq/kg on Day 1. Courses were repeated every 12 weeks. Response assessment was based on a change in the serum prostate specific antigen (PSA) levels, correlated with change in measurable disease and bone scan appearance. RESULTS: A greater than or equal to 50% decline in PSA for at least 6 weeks was observed in 21 patients (48%, 95% confidence interval, 33-62%). Median duration of response was 23 weeks (range, 6-70.8 weeks). The median survival was 13 months with 1- and 2-year survival rates of 55% and 25%, respectively. After completion of protocol therapy, a retrospective review showed that only nine patients received subsequent palliative external beam radiation after progression. CONCLUSIONS: The addition of strontium-89 to the regimen of EMP and vinblastine can be delivered safely and in repeated doses, provides effective palliation, and may decrease the need for future radiation therapy. A randomized trial is necessary to quantify these effects. Copyright 2002 American Cancer Society.
UI - 11920549
AU - Mishel MH; Belyea M; Germino BB; Stewart JL; Bailey DE Jr; Robertson C;
TI - Mohler J Helping patients with localized prostate carcinoma manage uncertainty and treatment side effects: nurse-delivered psychoeducational intervention over the telephone.
SO - Cancer 2002 Mar 15;94(6):1854-66
AD - School of Nursing, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA. email@example.com
BACKGROUND: The objective of this study was to test the efficacy of an individualized uncertainty management intervention delivered by telephone to Caucasian and African-American men with localized prostate carcinoma and directed at managing the uncertainties of their disease and treatment. METHODS: The authors delivered a psychoeducational intervention by phone to men with prostate carcinoma, with or without supplemented delivery to a close family member, that was directed at managing uncertainty and improving symptom control. One hundred thirty-four Caucasian men and 105 African-American men were assigned randomly to one of two approaches to delivering the intervention or to the control condition. Men entered the study immediately after surgical treatment or in the first 3 weeks of radiation therapy. Trained nurses delivered the intervention through weekly phone calls for 8 weeks. RESULTS: The authors found that the majority of intervention effects were from baseline to 4 months postbaseline, when treatment side effects are most intense. Both Caucasian men and African-American men who received either one of the two approaches for delivering the intervention improved in the two uncertainty management methods of cognitive reframing and problem solving. Similarly, when the intervention groups were combined, men who received the intervention also improved significantly in control of incontinence by 4 months postbaseline. Decreases in the number of treatment side effects differed by time and treatment/ ethnic group interactions as did satisfaction with sexual functioning. CONCLUSIONS: This is one of the first tests of a psychoeducational intervention among men with prostate carcinoma and was the first test that included a sufficient number of African-American men to test by ethnic group. Therefore, replication of these findings is advised. Copyright 2002 American Cancer Society.
UI - 11194637
AU - Neykov K; Panchev P
TI - [Bladder neck reconstruction after radical prostatectomy]
SO - Khirurgiia (Sofiia) 1999;55(5):5-7
AD - Medical University, Department of Urology, Sofia, Bulgaria.
Experience had with radical prostatectomy in patients presenting localized prostate carcinoma is shared. A modified technique for new bladder-neck formation contributing to continence preservation is used in five patients, yielding very good postoperative results. In four cases a full recovery of continence is achieved within 3 months of the operation without resorting to drug therapy. In one case medical treatment with parasympaticolytics and agonists of voluntary sphincter is applied. The final outcome is stress incontinence only and passage of urine in the event of micturition postponed with 3-3.5 hours.
UI - 11920502
AU - Sinibaldi VJ; Carducci MA; Moore-Cooper S; Laufer M; Zahurak M;
TI - Eisenberger MA Phase II evaluation of docetaxel plus one-day oral estramustine phosphate in the treatment of patients with androgen independent prostate carcinoma.
SO - Cancer 2002 Mar 1;94(5):1457-65
AD - Department of Oncology, Johns Hopkins Medical Institutions, Baltimore, Maryland 21205, USA. firstname.lastname@example.org
BACKGROUND: Recent clinical trials have shown antitumor activity with the combination of docetaxel plus estramustine phosphate (EMP) in the treatment of patients with androgen independent prostate carcinoma (AIPC). However, the most commonly employed treatment schedules with EMP have been associated with significant gastrointestinal, cardiovascular, and thromboembolic toxicity. The authors hypothesized that the therapeutic index of the combination of docetaxel plus EMP for patients with prostate carcinoma could be enhanced by reducing the incidence and severity of EMP-associated toxicity, which could be accomplished by shortening the duration of exposure to EMP. To preserve the therapeutic synergism between docetaxel and EMP, they designed a regimen employing higher doses of oral EMP administered on the day of the docetaxel infusion. METHODS: From June 1, 1998 through September 28, 2000, 42 patients with AIPC were registered to receive docetaxel (70 mg/m2 intravenously over 1 hour) and EMP (280 mg orally every 6 hours x 5 doses) every 21 days, up to a maximum of 6 cycles. Dexamethasone was administered prior to docetaxel and coumadin 2 mg orally every day was taken during the study treatment period. Patient characteristics included a median age of 68 years, a median Eastern Cooperative Oncology Group performance status of 1, a median prostate specific antigen (PSA) level at study entry of 110.5 ng/mL, and a median of 2 prior hormonal manipulations. Ten patients (25%) had received prior chemotherapy, and 14 patients (33%) had received prior palliative radiation therapy. RESULTS: Forty patients were evaluable for response and toxicity. Eighteen patients (45%; 95% confidence interval, 29-62%) had a decline > 50% in PSA level that lasted > 4 weeks with a median time to PSA progression and a median duration of PSA response of approximately 4.0 months. Four of 20 patients (20%) had partial soft tissue responses. Ten of 17 symptomatic patients (59%) had improvement in pain. The median survival for all patients was 13.5 months. The most prominent Grade 3 and 4 toxicities were reversible myelosuppression and fatigue. Nausea, emesis, diarrhea, and peripheral edema were minimal. No thromboembolic or hepatic complications were seen. CONCLUSIONS: Docetaxel plus 1 multidose day of oral EMP was active in patients with AIPC and was associated with an acceptable toxicity profile. Overall, the therapeutic index of this regimen compared favorably with regimens that employed a longer administration of EMP. Copyright 2002 American Cancer Society.
UI - 11919247
AU - DiPaola RS; Rinehart J; Nemunaitis J; Ebbinghaus S; Rubin E; Capanna T;
TI - Ciardella M; Doyle-Lindrud S; Goodwin S; Fontaine M; Adams N; Williams A; Schwartz M; Winchell G; Wickersham K; Deutsch P; Yao SL Characterization of a novel prostate-specific antigen-activated peptide-doxorubicin conjugate in patients with prostate cancer.
SO - J Clin Oncol 2002 Apr 1;20(7):1874-9
AD - Department of Medicine, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, New Brunswick 08901, USA. email@example.com
PURPOSE: To evaluate safety and pharmacokinetics (PK), and determine the recommended dose for efficacy studies, of L-377202, a novel peptide conjugate of doxorubicin (Dox) that releases the active metabolites leucine-doxorubicin (Leu-Dox) and Dox on cleavage by membrane-bound prostate-specific antigen (PSA). PATIENTS AND METHODS: Nineteen patients with advanced hormone-refractory prostate cancer were treated intravenously with 71 cycles of L-377202 at escalating dose levels of 20 (n = 1), 40 (n = 3), 80 (n = 4), 160 (n = 3), 225 (n = 6), and 315 mg/m(2) (n = 2) once every 3 weeks. Toxicity, response, and PK of L-377202 were assessed. RESULTS: L-377202 was well tolerated. Dose-limiting grade 4 neutropenia was noted in two of two patients administered 315 mg/m(2) (both patients were able to resume therapy at 225 mg/m(2)). The recommended dose for efficacy studies was 225 mg/m(2), which induced grade 4 neutropenia in one of six patients. PK studies demonstrated that L-377202 was metabolized to Leu-Dox and Dox. PK were linear; after administration of single doses of 225 mg/m(2), the mean area under the concentration-time profiles of L-377202, Leu-Dox, and Dox were 6 micromol x L/h, 4 micromol x L/h, and 1 micromol x L/h, and peak concentrations were 14 micromol/L, 5 micromol/L, and 120 nmol/L, respectively. At 225 and 315 mg/m(2), five patients completed at least three cycles of therapy; two patients had a greater than 75% decrease in PSA, and one patient had a stabilized PSA. No response was noted at dose levels less than 225 mg/m(2). CONCLUSION: This is the first study of selective drug delivery in humans using a novel PSA-activated agent. L-377202 was cleaved to produce detectable levels of the active metabolites Leu-Dox and Dox. L-377202 was well tolerated and established a safe dose level for further study.
UI - 11927294
AU - Hollenbeck BK; Dunn RL; Wei JT; McLaughlin PW; Han M; Sanda MG
TI - Neoadjuvant hormonal therapy and older age are associated with adverse sexual health-related quality-of-life outcome after prostate brachytherapy.
SO - Urology 2002 Apr;59(4):480-4
AD - Department of Urology, University of Michigan Hospital, Ann Arbor, Michigan 48109-0330, USA.
OBJECTIVES: Brachytherapy is increasingly used as a treatment for localized prostate cancer but information regarding long-term, postimplantation, patient-reported sexual health-related quality-of-life (HRQOL) is scant. Neoadjuvant hormonal therapy is commonly administered with brachytherapy, yet its potentially adverse effects on subsequent sexual health have not been described using a validated HRQOL instrument. We used a validated HRQOL survey to characterize the significance of neoadjuvant hormonal therapy and other baseline factors on postimplantation sexual function and impairment. METHODS: A cross-sectional survey using the expanded prostate cancer index composite HRQOL instrument was administered to all 114 localized prostate cancer patients who underwent ultrasound-guided, transperineal brachytherapy during a 4-year period and to 142 age-matched control men. Multivariable models measured the association of baseline factors and covariates with postimplantation sexual HRQOL. RESULTS: Older age (P = 0.01) and neoadjuvant hormonal therapy (P = 0.009) were independently associated with diminished sexual HRQOL after prostate brachytherapy. Among patients younger than 69 years old, 33% reported at least fair sexual function after brachytherapy alone compared with 19% of men after brachytherapy with neoadjuvant hormonal therapy. Of the age-matched control men younger than 69 years old, 78% reported at least fair sexual function. Among patients older than 69 years, 26% reported at least fair sexual function after brachytherapy alone compared with 5% after brachytherapy with neoadjuvant hormonal therapy, and 61% of age-matched controls reported at least fair sexual function. CONCLUSIONS: Patient age and neoadjuvant hormonal therapy are independent, significant determinants of sexual HRQOL after prostate brachytherapy. These factors should be taken into consideration when counseling patients with localized prostate cancer regarding the expected, postimplantation sexual HRQOL outcome.
UI - 11927313
AU - Ankem MK; DeCarvalho VS; Harangozo AM; Hartanto VH; Perrotti M; Han K;
TI - Shih WJ; Malka E; White EC; Maggio R; Ioffreda R; Goldsmith JW; Weiss RE Implications of radioactive seed migration to the lungs after prostate brachytherapy.
SO - Urology 2002 Apr;59(4):555-9
AD - Division of Urology, Robert Wood Johnson Medical School University of Medicine and Dentistry of New Jersey, New Brunswick, New Jersey 08903-0019, USA.
OBJECTIVES: To review the incidence and the impact of pulmonary seed migration after prostate brachytherapy on lung function. Isolated reports of seed migration to the lungs after prostate brachytherapy have been published; however, the clinical consequences of this pulmonary migration have not been adequately evaluated. METHODS: We performed a retrospective review of patients undergoing prostate brachytherapy from 1998 to 2000. Pulmonary imaging with chest x-ray was performed 15 to 90 days (median 45) after the procedure. The chest radiographs were reviewed by a single radiologist (V.S.D.), and patients with seed migration to the lungs were evaluated by a single pulmonologist (A.M.H.) using a questionnaire, chest radiography, and pulmonary function tests. Computed tomography of the prostate after seed implantation was performed to check seed position and dosimetry. Odds ratio, confidence intervals, chi-square tests, and logistic regression analysis were performed to evaluate the relationship between the type and number of seeds used, the incidence of pulmonary migration, and the effects on pulmonary function. RESULTS: A total of 83 patients underwent prostate brachytherapy during the study period and 58 patients underwent chest radiography. Seed migration occurred in 21 (36.2%) of 58 patients (95% confidence interval 23.8% to 48.6%). Thirty-four (0.71%) of 4755 seeds used migrated to the lungs. Nine patients had single seed migration to the right lung and three to the left lung. Nine patients had multiple (maximum of 4) and bilateral seed migration. No consistent relationship was found between seed migration and the type of seeds used (P = 0.24). Borderline statistical significance suggested an increased incidence of seed migration with an increasing number of implanted seeds (P = 0.054). Repeat chest radiography in 21 patients revealed no delayed migration at a median follow-up of 16 months. Clinical and pulmonary function testing revealed no consistent abnormality attributable to seed migration. CONCLUSIONS: Radioactive seed migration occurred in 36.2% of brachytherapy patients who had chest radiographs done in our series. Pulmonary seed migration may be influenced by the number of implanted seeds and does not appear to be influenced by the seed type. Additional study of this observed phenomenon is required. A thorough pulmonary workup failed to reveal any short-term harmful side effects; however, long-term follow-up is needed. Healthcare providers should discuss the possibility of pulmonary seed migration with patients with prostate cancer considering prostate brachytherapy.
UI - 11937432
AU - Moyad MA
TI - Selenium and vitamin E supplements for prostate cancer: evidence or embellishment?
SO - Urology 2002 Apr;59(4 Suppl 1):9-19
AD - Department of Urology, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0330, USA. firstname.lastname@example.org
Selenium and vitamin E are probably 2 of the most popular dietary supplements considered for use in the reduction of prostate cancer risk. This enthusiasm is reflected in the initiation of the Selenium and Vitamin E Chemoprevention Trial (SELECT). Is there sufficient evidence to support the use of these supplements in a large-scale prospective trial for patients who want to reduce the risk of prostate cancer? Results from numerous laboratory and observational studies support the use of these supplements, and data from recent prospective trials also add partial support. However, a closer analysis of the data reveals some interesting and unique associations. Selenium supplements provided a benefit only for those individuals who had lower levels of baseline plasma selenium. Other subjects, with normal or higher levels, did not benefit and may have an increased risk for prostate cancer. The concept that supplements reduce prostate cancer risk only in those at a higher risk and/or those with lower plasma levels of these compounds is supported by trials examining beta-carotene supplements. Smokers may be the only individuals who benefit, as has also been shown with vitamin E supplementation. In 4 recent prospective studies, vitamin E was found to reduce the risk of prostate cancer in past/recent and current smokers and those with low levels of this vitamin. Vitamin E supplements in higher doses (> or =100 IU) were also associated with a higher risk of aggressive or fatal prostate cancer in nonsmokers from a past prospective study. The dose of vitamin E in the SELECT trial (400 IU/day) is 8 times higher than what has been suggested to be effective (50 IU/day) by the largest randomized prospective trial in which the incidence rate of prostate cancer was used as an endpoint. Recent research also suggests that dietary vitamin E may be associated with a lower risk of prostate cancer than the vitamin E supplement. Additionally, recent results from all past cardiovascular prospective, randomized trials suggest that vitamin E shows little benefit for cardiovascular disease risk, especially at the dose being used in the SELECT trial. Other intriguing positive findings from past prospective studies of supplements suggest that aspirin and other nonsteroidal anti-inflammatory drugs have a role in reducing the risk of prostate cancer or other types of cancer (eg, colon cancer). It may be time to conduct a large costly trial to reconsider the use of selenium and vitamin E supplements for the reduction of prostate cancer risk. Some evidence for the use of these supplements exists, but serious embellishment of study findings may be leading to an inappropriate use of these supplements in a clinical setting.
UI - 11115157
AU - Lotem M; Hubert A; Lyass O; Goldenhersh MA; Ingber A; Peretz T; Gabizon
TI - A Skin toxic effects of polyethylene glycol-coated liposomal doxorubicin.
SO - Arch Dermatol 2000 Dec;136(12):1475-80
AD - Sharett Institute of Oncology, Hadassah Hebrew University Medical Center, Kiryat Hadassah, PO Box 12000, Jerusalem 91120, Israel. email@example.com
OBJECTIVES: To record the profile of toxic effects of polyethylene glycol-coated liposomal doxorubicin hydrochloride (Doxil) to the skin, and to evaluate whether the long circulation pattern and enhanced accumulation of liposomes in specific skin sites will result in any unique presentations. DESIGN: Patients were accrued in the frame of dose-range-finding studies that examine the toxic effects and antitumor activity of Doxil therapy in metastatic breast and prostate cancers. All patients receiving Doxil were instructed to report any skin eruption or discomfort. Skin examination was performed on a regular basis at every cycle of Doxil therapy and after specific complaints. SETTING: Outpatient day care unit of the oncology institute of a secondary-referral medical center. PATIENTS: Sixty patients (45 women and 15 men). MAIN OUTCOME MEASURES: A basic severity scale of I through IV was adopted for toxic effects to the skin, based on National Cancer Institute common toxicity criteria. RESULTS: The following 4 patterns of skin eruptions were encountered: hand-foot syndrome (n = 24), diffuse follicular rash (n = 6), intertrigolike eruption (n = 5), and new formation of melanotic macules (n = 3). Another major toxic effect of Doxil was stomatitis, which was found to be the dose-limiting factor for the maximal single dose. Alopecia and extravasation injuries did not occur. CONCLUSIONS: The profile of toxic effects of Doxil to the skin reflects its unique pharmacokinetics and tissue distribution. These skin reactions vary significantly from those associated with doxorubicin in non-liposome-encapsulated form.
UI - 11458039
AU - Han M; Partin AW; Piantadosi S; Epstein JI; Walsh PC
TI - Era specific biochemical recurrence-free survival following radical prostatectomy for clinically localized prostate cancer.
SO - J Urol 2001 Aug;166(2):416-9
AD - Departments of Urology, Oncology Biostatistics and Pathology, James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
PURPOSE: We retrospectively reviewed a large series of men with clinically localized prostate cancer who underwent surgery to define the extent of stage migration and its influence on biochemical recurrence in 3 different eras of prostate cancer management. MATERIALS AND METHODS: A total of 2,370 men were treated with radical prostatectomy from 1982 to 1998. We analyzed the freedom from biochemical (prostate specific antigen) progression after radical prostatectomy. We compared the distribution of pathological stage by the year of surgery. We then compared the biochemical recurrence-free survival rate according to the different eras that reflect a change in prostate cancer management. RESULTS: There was a significant downward stage migration of prostate cancer and an increasing proportion of men who presented with organ confined disease in recent years. The actuarial biochemical recurrence-free rate was significantly different for patients who underwent surgery between 1982 and 1988, compared with those between 1989 and 1998 (p <0.001). These changes may have reflected the benefits of early detection with prostate specific antigen and digital rectal examination, better preoperative selection of patients for surgery as well as the effect of lead time. CONCLUSIONS: Widespread early detection programs for prostate cancer resulted in downward stage migration in men presenting with prostate cancer at our institution during the last 18 years. Also, we have demonstrated a biochemical recurrence-free survival advantage, probably secondary to an improved therapeutic outcome as well as lead time bias, in men who underwent surgery between 1989 and 1998, compared with those between 1982 and 1988. When trying to compare the efficacy of different treatment modalities for prostate cancer, the era in which patients underwent therapy is an important factor to be considered.
UI - 11490237
AU - Zelefsky MJ; Fuks Z; Hunt M; Lee HJ; Lombardi D; Ling CC; Reuter VE;
TI - Venkatraman ES; Leibel SA High dose radiation delivered by intensity modulated conformal radiotherapy improves the outcome of localized prostate cancer.
SO - J Urol 2001 Sep;166(3):876-81
AD - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
PURPOSE: We present the long-term outcome and tolerance of 3-dimensional (D) conformal and intensity modulated radiation therapy for localized cancer were treated with 3-D conformal or intensity modulated radiation therapy. Patients were categorized into prognostic risk groups based on pretreatment prostate specific antigen (PSA), Gleason score and clinical stage. Sextant biopsies were performed 2.5 years or greater after treatment to assess local control. PSA relapse was defined according to the consensus guidelines of the American Society for Therapeutic Radiation Oncology. Late toxicity was classified according to the Radiation Therapy Oncology Group morbidity grading scale. Median followup was 60 months. RESULTS: At 5 years the PSA relapse-free survival rate in patients at favorable, intermediate and unfavorable risk was 85% (95% confidence interval [CI] +/- 4), 58% (95% CI +/- 6) and 38% (95% CI +/- 6), respectively (p <0.001). Radiation dose was the most powerful variable impacting PSA relapse-free survival in each prognostic risk group. The 5-year actuarial PSA relapse-free survival rate for patients at favorable risk who received 64.8 to 70.2 Gy. was 77% (95% CI +/- 8) compared to 90% (95% CI +/- 8) for those treated with 75.6 to 86.4 Gy. (p = 0.04) [corrected]. The corresponding rates were 50% (95% CI +/- 8) versus 70% (95% CI +/- 6) in intermediate risk cases (p = 0.001), and 21% (95% CI +/- 8) versus 47% (95% CI +/- 6) in unfavorable risk cases (p = 0.008) [corrected]. Only 4 of 41 patients (10%) who received 81 Gy. had a positive biopsy 2.5 years or greater after treatment compared with 27 of 119 (23%) after 75.6, 23 of 68 (34%) after 70.2 and 13 of 24 (54%) after 64.8 Gy. The incidence of toxicity after 3-D conformal radiation therapy was dose dependent. The 5-year actuarial rate of grade 2 rectal toxicity in patients who received 75.6 Gy. or greater was 14% (95% CI +/- 2) compared with 5% (95% CI +/- 2) in those treated at lower dose levels (p <0.001). Treatment with intensity modulated radiation therapy significantly decreased the incidence of late grade 2 rectal toxicity since the 3-year actuarial incidence in 189 cases managed by 81 Gy. was 2% (95% CI +/- 2) compared with 14% (95% CI +/- 2) in 61 managed by the same dose of 3-D conformal radiation therapy (p = 0.005). The 5-year actuarial rate of grade 2 urinary toxicity in patients who received 75.6 Gy. or greater 3-D conformal radiation therapy was 13% compared with 4% in those treated up to lower doses (p <0.001). Intensity modulated radiation therapy did not affect the incidence of urinary toxicity. CONCLUSIONS: Sophisticated conformal radiotherapy techniques with high dose 3-D conformal and intensity modulated radiation therapy improve the biochemical outcome in patients with favorable, intermediate and unfavorable risk prostate cancer. Intensity modulated radiation therapy is associated with minimal rectal and bladder toxicity, and, hence, represents the treatment delivery approach with the most favorable risk-to-benefit ratio.