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NCI CANCERLIT^® Search: Therapy of Prostate Cancer - October 2002

National Cancer Institute^®
Last Modified: October 1, 2002

Suicide gene therapy for urogenital cancer: current outcome and prospects.
Altered cognitive function in men treated for prostate cancer with luteinizing hormone-releasing hormone analogues and cyproterone acetate:
Epidemiology of radical prostatectomy for localized prostate cancer in the era of prostate-specific antigen: an overview of the Department of
The value of PSA measurements at 30 Gy, 50 Gy and 60 Gy for dose limitation in patients with radiotherapy for PSA increase after radical
Can vasectomy reduce the incidence of prostatic tumor?
[Immunogenicity of synthetic sex hormones and thrombogenesis]
In the public's view...screening but not seeing.
Molecular staging of pelvic surgical margins after radical prostatectomy: comparison of RT-PCR for prostate-specific antigen and
Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis in androgen-independent human prostate cancer cell lines.
Pneumonitis associated with nonsteroidal antiandrogens: presumptive evidence of a class effect.
The management of localized prostate cancer.
Intensity-modulated radiation therapy for prostate cancer.
Nursing assessment of sexual function following permanent prostate brachytherapy for patients with early-stage prostate cancer.
[Urology]
Novel therapies for the treatment of prostate cancer: current clinical trials and development strategies.
Transperineal interstitial permanent prostate brachytherapy for carcinoma of the prostate.
Decision-making models in the analysis of portal films: a clinical pilot study.
The effects of information and negative affect on severity of side effects from radiation therapy for prostate cancer.
A comprehensive and novel predictive modeling technique using detailed pathology factors in men with localized prostate carcinoma.
Treatment of patients with clinical T3 prostate cancer.
Liposomal doxorubicin (Caelyx) in symptomatic androgen-independent prostate cancer (AIPC)--delayed response and flare phenomenon should be
Cancer flourishes.
Prostate cancer: metastatic.
Prostate cancer: non-metastatic.
Diethylstilbesterol revisited: androgen deprivation, osteoporosis and prostate cancer.
Herbal supplement PC-Spes for prostate cancer.
State-of-the-art treatment of metastatic hormone-refractory prostate cancer.
Controversies surrounding androgen deprivation for prostate cancer.
A critical analysis of the interpretation of biochemical failure in surgically treated patients using the American Society for Therapeutic
Photodynamic therapy for prostate cancer recurrence after radiotherapy: a phase I study.
Unusual anti-angiogenic effect of combined hormonal blockade.
Prompt resolution of acute disseminated intravascular coagulation with docetaxel and cisplatin in hormone refractory prostate cancer.
Re: Diethylstilbesterol revisited: androgen deprivation, osteoporosis and prostate cancer.
Prostate perfusion in patients with locally advanced prostate carcinoma treated with different hyperthermia techniques.
Complete scintigraphic lesion regression after single 153Sm-EDTMP therapy in prostate cancer.
Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate
Editorial: the coming revolution in the treatment of prostate cancer patients.
Hormonal therapy of prostate cancer.
Neoadjuvant strategies for prostate cancer prior to radical prostatectomy.
Therapeutic considerations for patients with high-risk, nonmetastatic, prostate cancer.
Secondary hormonal manipulation of prostate cancer.
Chemotherapy for androgen-independent prostate cancer.
Periodic health examination, 1991 update: 3. Secondary prevention of prostate cancer. Canadian Task Force on the Periodic Health Examination.
Which results justify the means in prostate cancer treatment?
An evidence-based analysis of the management of localized prostate cancer.
Dose/volume relationship of late rectal bleeding after external beam radiotherapy for localized prostate cancer: absolute or relative rectal
I-125 versus Pd-103 for low-risk prostate cancer: morbidity outcomes from a prospective randomized multicenter trial.
Perineural invasion is not predictive of biochemical outcome following prostate brachytherapy.
Minimal blood loss in patients undergoing radical retropubic prostatectomy.
Complementary and alternative medicine use among men with prostate cancer in 4 ethnic populations.
What influences family physicians' cancer screening decisions when practice guidelines are unclear or conflicting?
Should bisphosphonates be used routinely in patients with prostate cancer metastatic to bone?
A randomized, placebo-controlled trial of zoledronic acid in patients with hormone-refractory metastatic prostate carcinoma.
Risk group dependence of dose-response for biopsy outcome after three-dimensional conformal radiation therapy of prostate cancer.
Considerations on treatment efficiency of different conformal radiation therapy techniques for prostate cancer.
Clinical outcome of patients with lymph node positive prostate cancer after radical prostatectomy versus androgen deprivation.
The relevance of prostatectomy findings for brachytherapy selection in patients with localized prostate carcinoma.
Clinical oncologists favour radical radiotherapy for localized prostate cancer: a questionnaire survey.
Three-month neoadjuvant hormonal therapy before radical prostatectomy: a 7-year follow-up of a randomized controlled trial.
(125)Iodine prostate brachytherapy: outcome from the first 100 consecutive patients and selection strategies incorporating urodynamics.
Oat-cell carcinoma of the prostate. Diagnosis, prognosis and therapeutic implications.
Chemosensitivity of human prostate cancer cells PC3 and LNCaP to genistein isoflavone and beta-lapachone.
Analysis of the recurrence in relation to the plannings target volume (PTV) for brachytherapy or external beam radiation therapy (EBRT).
[Updating in prevention and treatment of prostate cancer]
Prostate specific antigen testing for prostate cancer.
Quality improvement report: Improving design and conduct of randomised trials by embedding them in qualitative research: ProtecT (prostate
1.5-D high intensity focused ultrasound array for non-invasive prostate cancer surgery.
Phase I study of a vaccine using recombinant vaccinia virus expressing PSA (rV-PSA) in patients with metastatic androgen-independent prostate
Defining sexual outcomes after treatment for localized prostate carcinoma.
Genistein and vitamin D synergistically inhibit human prostatic epithelial cell growth.
Prostate cancer: detection and patient involvement in treatment.
Prostate cancer detection and patient involvement in treatment.
The dilemma of hereditary prostate cancer.
Is the alpha/beta ratio for prostate cancer low?
[Histopathological changes of prostate cancer after castration therapy and correlative factors]
Edema-induced increase in tumour cell survival for 125I and 103Pd prostate permanent seed implants--a bio-mathematical model.
Transutricular seminal vesiculoscopy.
Long-term durability of PSA failure-free survival after radiotherapy for localized prostate cancer.
Dose response in prostate cancer with 8-12 years' follow-up.
Changing prostate-specific antigen outcome after surgery or radiotherapy for localized prostate cancer during the prostate-specific antigen era.
Acute symptoms, not rectally administered sucralfate, predict for late radiation proctitis: longer term follow-up of a phase III
Prostate-specific antigen spikes after permanent prostate brachytherapy.
Yes, the alpha/beta ratio for prostate cancer is low or "methinks the lady doth protest too much...about a low alpha/beta that is".

1
UI - 12006245
AU - Nasu Y; Kusaka N; Saika T; Tsushima T; Kumon H
TI - Suicide gene therapy for urogenital cancer: current outcome and prospects.
SO - Mol Urol 2000 Summer;4(2):67-71
AD - Department of Urology, Okayama University Medical School, Shikata, Okayama, Japan. ynasu@med.okayama-u.ac.jp
Viral-mediated transfer of the herpes simplex virus thymidine kinase (HSV-tk) gene has been demonstrated by several investigators to confer sensitivity to nucleoside analogs such as ganciclovir (GCV) in a variety of tumor cells including brain, prostate, bladder, kidney, ovary, head and neck, lung, pancreas, and liver cancers. Fourteen suicide gene clinical protocols using adenovirus vectors have been conducted, including four in prostate cancer. Two additional protocols for prostate cancer are in preparation in Japan and the Netherlands. A study conducted at Baylor College of Medicine was the first to demonstrate the safety of HSV-tk plus GCV therapy for human prostate cancer and the anticancer activity of gene therapy in this disease. However, it is still in the early stage of its development, with a number of problems to be overcome. Systemic delivery, specific introduction, and specific expression of the target gene are the major issues to be managed in order to establish a clinically relevant treatment strategy.

2
UI - 12175403
AU - Green HJ; Pakenham KI; Headley BC; Yaxley J; Nicol DL; Mactaggart PN;
TI - Swanson C; Watson RB; Gardiner RA Altered cognitive function in men treated for prostate cancer with luteinizing hormone-releasing hormone analogues and cyproterone acetate: a randomized controlled trial.
SO - BJU Int 2002 Sep;90(4):427-32
AD - School of Psychology and Department of Surgery, The University of Queensland, Queensland, Australia.
OBJECTIVE: To report the first systematic investigation of the cognitive effects of luteinizing hormone-releasing hormone (LHRH) analogues in male patients, as LHRH analogues have been associated with memory impairments in women using these drugs for gynaecological conditions. PATIENTS AND METHODS: Eighty-two men with extraprostatic prostate cancer were randomly assigned to receive either continuous leuprorelin, goserelin (both LHRH analogues), cyproterone acetate (a steroidal antiandrogen) or close clinical monitoring. These patients underwent cognitive assessments at baseline and before starting treatment (77), and then 6 months later (65). RESULTS: Compared with the baseline assessments, men receiving androgen suppression monotherapy performed worse in two of 12 tests of attention and memory; 24 of 50 men randomized to active treatment and assessed 6 months later had a clinically significant decline in one or more cognitive tests but not one patient randomized to close monitoring showed a decline in any test performance. CONCLUSION: Pharmacological androgen suppression monotherapy for prostate cancer may be associated with impaired memory, attention and executive functions.

3
UI - 12219014
AU - Moul JW; Wu H; Sun L; McLeod DG; Amling C; Lance R; Kusuda L; Donahue T;
TI - Foley J; Chung A; Sexton W; Soderdahl D; Rich NM Epidemiology of radical prostatectomy for localized prostate cancer in the era of prostate-specific antigen: an overview of the Department of Defense Center for Prostate Disease Research national database.
SO - Surgery 2002 Aug;132(2):213-9
AD - Urology Service, Dept of Surgery, Walter Reed Army Medical Center, Washington, DC, USA.
BACKGROUND: Because of public awareness and screening, the incidence of clinically localized prostate cancer has increased dramatically in the last 15 years. The Department of Defense Center for Prostate Disease Research (CPDR) was established by the US Congress in 1991 to study prostate cancer in the US military health care system. A key component of CPDR is a multicenter prospective and retrospective prostate research database that collects comprehensive standardized data on all consenting patients. To verify and document changes in the epidemiology of men electing radical prostatectomy (RP) as primary treatment for their localized prostate cancer, we undertook an analysis of such cases when the PSA screening test became widely available and used. METHODS: The CPDR database consists of standardized data collection forms for each episode of care completed prospectively, and in some cases, retrospectively, on men with prostate cancer and those undergoing a prostate biopsy for presumed cancer at participating medical centers. In December 31, 2000, was conducted, revealing 3681 cases for analysis from 9 hospital sites. These cases were analyzed over time (calendar year), and changes in the characteristics of the patients, disease severity, and surgical results were compared. RESULTS: There was a significant shift to younger men undergoing RP with the median age declining to 62.3 years old by 2000, and more than 40% of the men were less than 60 years old. There was an increase in African-Americans undergoing RP and a large increase in clinical stage T1 disease candidates of both races representing 56.5% of men by 2000. There was a large increase in patients having pretreatment PSA levels between 4 and 10 ng/mL (59.2% by 2000). Retropubic approach was predominant (over 80%) and was associated with a much lower blood loss by 2000 (approximately 800 mL). There was an increase in use of nerve-sparing procedures, and operative time declined significantly to a median of 3.5 hours by 2000. Finally, there was a marked surgical stage migration with a higher proportion of men with organ-confined disease and negative surgical margins; by 2000, 63.4% had pT2 disease. The early outcomes improved with a 1-year disease-free survival in excess of 93%. CONCLUSIONS: RP is being performed more commonly on younger men with earlier stage disease in the PSA era. The operation is now performed more rapidly with less blood loss, and the surgical pathology outcome end points and early disease-free survival are improved. These results portend well for improved long-term outcomes of surgical therapy.

4
UI - 12240547
AU - Wiegel T; Bottke D; Bandlow P; Steiner U; Hinkelbein W
TI - The value of PSA measurements at 30 Gy, 50 Gy and 60 Gy for dose limitation in patients with radiotherapy for PSA increase after radical prostatectomy.
SO - Strahlenther Onkol 2002 Aug;178(8):422-5
AD - Department of Radiotherapy, University Hospital Benjamin Franklin, Freie Universitat Berlin, Germany. wiegel@ukbf.fu.berlin.de
BACKGROUND: Radiation therapy is a treatment option for patients with rising PSA after radical prostatectomy without histological evidence of local relapse and no signs of distant metastases. Prior to radiotherapy there is no certainty whether a patient is going to respond to the treatment or not. When total doses of more than 60 Gy are given there is an exponential rise in treatment-related late toxicity. Therefore those patients in whom radiotherapy later appears to be ineffective may benefit from a dose restriction to 50-60 Gy. The aim of this study was to examine the prognostic value of PSA levels evaluated during radiotherapy. PATIENTS AND METHODS: 41 patients with rising PSA level following prostatectomy received radiotherapy to the prostatic bed and were treated up to a median dose of 66.6 Gy. We evaluated serum PSA levels during radiotherapy at 30 Gy, 50 Gy, and 60 Gy and compared them to the pre-radiotherapy PSA level and the outcome of radiotherapy. RESULTS: After radiotherapy, 31 patients (76%) had either undetectable (n = 15), or decreasing but still detectable PSA levels (n = 16) and ten patients (24%) had rising PSA levels and did not respond. PSA evaluation at 30 Gy showed that 26% (8/31) of those patients who would respond to radiotherapy still had a rising PSA when compared to pretreatment PSA. At 50 Gy and 60 Gy 93% (27/29) of these patients had decreasing PSA levels. In contrast, 75% (6/8) and 88% (7/8) of those patients in whom radiotherapy was not effective had rising PSA levels at 50 Gy and 60 Gy (p < 0.05). CONCLUSIONS: PSA measurements at 30 Gy, 50 Gy and 60 Gy for radiotherapy of PSA increase following radical prostatectomy without histologically proven local recurrence gives valuable information about the later tumor response. Therefore it possibly gives the opportunity to finish radiotherapy between 50 and 60 Gy, as almost all patients with continued PSA increase at 60 Gy do not stand to profit from radiotherapy. In these patients dose limitation would significantly decrease the risk of late side effects, especially for the bladder and the rectum. PSA evaluations at 30 Gy and 50 Gy or 60 Gy are recommendable.

5
UI - 7045601
AU - Sheth AR; Panse GT
TI - Can vasectomy reduce the incidence of prostatic tumor?
SO - Med Hypotheses 1982 Mar;8(3):237-41
Results from our laboratory have revealed that seminal plasma concentration of acid phosphatase, maltase, prolactin, citric acid, zinc and magnesium which are the secretory products of the prostate gland, decreased significantly in vasectomized men compared to those in controls namely normal fertile men. Further, it was observed that the decrease in prostatic function was not related to the time since vasectomy. Considering these two facts together, we propose that vasectomy may lead to decrease in the incidence of prostatic tumors - a disease that claims nearly 22,000 lives each year in the United States alone.

6
UI - 3892453
AU - Beaumont V; Beaumont JL
TI - [Immunogenicity of synthetic sex hormones and thrombogenesis]
SO - Pathol Biol (Paris) 1985 Apr;33(4):245-9
The ingestion of synthetic steroidal and non-steroidal estrogens may induce antiestrogen antibodies in women on oral contraceptives, and in prostatic patients treated with diethylstilbestrol (DES). Natural sex hormones have no such effect. A radioimmunoassay with tritiated ethinylestradiol or DES was applied to study the prevalence of synthetic sex hormone antibodies in 2 populations: 100 women on estroprogestative hormones and 93 cases of DES treated prostatic cancers. Homologous non-treated controls were compared. Results allowed to identify among treated and asymptomatic subjects an immunoreactive population of 30% women and 47% men. Furthermore, the antibodies were found with a much higher frequency (p less than 0.001) in patients who had experienced a thromboembolic disease while on treatment: 90% of women and 74% of men. The importance of these antibodies as a risk factor, their possible role in promoting vascular lesions, the interest of their detection for the prevention of the vascular risk induced by synthetic sex hormones, are considered.

7
UI - 9176597
AU - Goodman NW
TI - In the public's view...screening but not seeing.
SO - Br J Hosp Med 1997 Mar 5-18;57(5):201
AD - Department of Anaesthesia, Southmead Hospital, Bristol.

8
UI - 11956625
AU - Straub B; Muller M; Krause H; Goessl C; Schrader M; Heicappell R; Miller
TI - K Molecular staging of pelvic surgical margins after radical prostatectomy: comparison of RT-PCR for prostate-specific antigen and telomerase activity.
SO - Oncol Rep 2002 May-Jun;9(3):545-9
AD - Department of Urology, Klinikum Benjamin Franklin, Freie Universitat Berlin, D-12200 Berlin, Germany. straub@medizin.fu-berlin.de
The further course of prostate cancer (PC) after radical prostatectomy (RPX) is decisively influenced by the local tumor stage. Although it is now possible to assess the risk of local recurrence from the histopathology, precise predictions cannot be made. A more accurate evaluation would be desirable, mainly for early planning of adjuvant therapy. We assessed the detection of telomerase activity using the Telomeric Repeat Amplification Protocol in surgical margins compared to RT-PCR-supported prostate-specific antigen (PSA) mRNA detection and conventional histopathological examination. We examined 95 patients with local PC during RPX and 16 patients with muscle-invasive transitional bladder cancer who underwent radical cystectomy. After RPX or RCX biopsies were obtained from 4 or 3 defined areas of the prostatic fossa and processed by TRAP assay for telomerase activity and by RT-PCR for PSA using a standard protocol. Five of 48 patients (10.4%) with organ-confined prostate cancer (pT2) and 7 of 47 patients (14.9%) with locally advanced PC (>pT2) had positive detection of telomerase activity in at least one positive specimen. In contrast to RT-PCR for PSA mRNA and histological findings for organ-confined and locally advanced disease, detection of telomerase activity yielded no statistically significant correlation to clinical parameters. Only PC-patients with positive histopathological margins had a positive correlation between detection of telomerase activity and high Gleason scores (r=0.65, p=0.022). Based on the results obtained and the current state of knowledge, measurement of telomerase activity must be considered less sensitive than RT-PCR for PSA mRNA in surgical margins, although tumor specificity should theoretically be higher. It is not even sure at the present time whether a combination of both methods offers any recognizable advantage over PSA mRNA detection alone. The value of the results obtained in this study will have to be assessed in a further follow-up to determine whether patients with positive molecular detection have an increased risk of local recurrence.

9
UI - 12235008
AU - Kim IY; Kim BC; Seong do H; Lee DK; Seo JM; Hong YJ; Kim HT; Morton RA;
TI - Kim SJ Raloxifene, a mixed estrogen agonist/antagonist, induces apoptosis in androgen-independent human prostate cancer cell lines.
SO - Cancer Res 2002 Sep 15;62(18):5365-9
AD - Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute/NIH, Building 41, Room C629, 9000 Rockville Pike, Bethesda, MD 20892, USA.
Raloxifene, a selective estrogen receptor (ER) modulator, is a mixed estrogen agonist/antagonist that has been shown to prevent osteoporosis and breast cancer in women. Because the prostate contains high levels of ER-beta, the present study investigated the effect of raloxifene in three well-characterized, androgen-independent human prostate cancer cell lines: (a) PC3; (b) PC3M; and (c) DU145. Reverse transcriptase-PCR and Western blot analysis for ER-alpha and ER-beta demonstrated that all three cell lines express ER-beta, whereas only PC3 and PC3M cells were positive for ER-alpha. After the treatment with raloxifene, a dramatic increase in cell death was observed in a dose-dependent manner in the three prostate cancer cell lines (10(-9) to 10(-6) M range). Because the three prostate cancer cell lines demonstrated similar morphological changes after the raloxifene treatment, PC3 (ER-alpha/ER-beta+) and DU145 (ER-beta+ only) cells were selected to further characterize the raloxifene-induced cell death. Using the nucleus-specific stain 4',6-diamidino-2-phenylindole, nuclear fragmentation was observed in a time-dependent manner in both cell lines after exposure to 10(-6) M raloxifene. Using the terminal deoxynucleotidyl transferase-mediated nick end labeling apoptotic assay, it was demonstrated that the nuclear fragmentation was caused by apoptosis. To investigate the possibility that caspase activation is involved in raloxifene-induced apoptosis, cells were treated with the pan-caspase inhibitor ZVAD. The results demonstrated that the dramatic change in cellular morphology after treatment with raloxifene was no longer observed when cells were pretreated with ZVAD. Immunoblot demonstrated activation of caspases 8 and 9 in PC3 and DU145 cells, respectively. Taken together, these results demonstrate that the mixed estrogen agonist/antagonist, raloxifene, induces apoptosis in androgen-independent human prostate cancer cell lines.

10
UI - 12353966
AU - Bennett CL; Raisch DW; Sartor O
TI - Pneumonitis associated with nonsteroidal antiandrogens: presumptive evidence of a class effect.
SO - Ann Intern Med 2002 Oct 1;137(7):625

11
UI - 8777510
AU - Clarke NW
TI - The management of localized prostate cancer.
SO - Br J Hosp Med 1996 Mar 6-19;55(5):232-3

12
UI - 12118388
AU - Zelefsky MJ; Fuks Z; Leibel SA
TI - Intensity-modulated radiation therapy for prostate cancer.
SO - Semin Radiat Oncol 2002 Jul;12(3):229-37
AD - Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. Zelefskm@mskcc.org
Intensity-modulated radiation therapy (IMRT) represents a new paradigm in radiation treatment planning and delivery for treatment of prostate cancer with enormous potential. Preliminary data indicate that this highly conformal treatment technique can effectively reduce acute and late-occurring toxicities, improving the quality of life of the treated patient and serving as the optimal dose escalation tool. IMRT produces radiation distributions capable of delivering different dose prescriptions to multiple target sites, providing a new opportunity for differential dose painting to increase the dose selectively to specific, image-defined regions within the prostate. Clinical trials will be necessary to define more clearly the true extent of improved tumor control and reduction in normal tissue complications with IMRT in the treatment of prostate cancer. Copyright 2002, Elsevier Science (USA). All rights reserved.

13
UI - 12240487
AU - Stipetich RL; Abel LJ; Blatt HJ; Galbreath RW; Lief JH; Butler WM;
TI - Merrick GS Nursing assessment of sexual function following permanent prostate brachytherapy for patients with early-stage prostate cancer.
SO - Clin J Oncol Nurs 2002 Sep-Oct;6(5):271-4
AD - schifonc@wheelinghosp.com
Assessment of sexual function following potentially curative local treatment for carcinoma of the prostate gland has resulted in wide ranges of potency preservation rates, which may be because of differences in the evaluated patient populations, mode of data collection, and length of patient follow-up. Quality-of-life data are most reliable when obtained by patient-administered and validated quality-of-life instruments. In the Schiffler Cancer Center's prostate brachytherapy unit, healthcare professionals utilize the specific erectile questions of the International Index of Erectile Function to ascertain pre- and post-treatment erectile function. Documentation of sexual function following all local treatments, including prostate brachytherapy, may help to clarify the etiology of treatment-induced erectile dysfunction (ED), improve treatment for ED, and, ultimately, improve quality-of-life outcomes. Fortunately, the majority of patients with brachytherapy-induced ED respond favorably to sildenafil citrate.

14
UI - 12355941
AU - Hinotsu S; Akaza H
TI - [Urology]
SO - Gan To Kagaku Ryoho 2002 Sep;29(9):1549-69
AD - Department of Urology, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
We reviewed comparative clinical studies for prostate cancer and bladder cancer performed in Japan. A systematic search was done using PubMed and Icyushi WEB to find randomized clinical trials and the result was verified. Each manuscript was summarized according to the seven items of stage, entry period, exposure, endpoint, sample size, method of randomization and result. Forty reports were found as randomized clinical trials for prostate cancer, and sixty-two reports were identified for bladder cancer. Most exposures for advanced prostate cancer were hormonal therapy involving intravesical instillation after transurethral resection for superficial bladder cancer. At minimum, we have clarified that large scale randomized trials have been conducted in Japan for both prostate cancer and bladder cancer.

15
UI - 12031864
AU - Morris MJ; Scher HI
TI - Novel therapies for the treatment of prostate cancer: current clinical trials and development strategies.
SO - Surg Oncol 2002 Jun;11(1-2):13-23
AD - Department of Genitourinary Oncology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 444, New York, NY 10021, USA. morrism@mskcc.org
The number of treatment options for patients with prostate cancer is expanding, as mechanism-based therapies enter clinical testing. Such strategies are based on manipulating tumoral genetics, cell signaling, apoptosis, angiogenesis, the immune system, and others. To properly develop these agents, traditional trial designs and outcome measures require reconsideration. This review describes these novel drugs and their targets using a clinical states model. Investigators use a clinical states model as a framework for matching specific agents with the needs of the treatment population and the biology of the tumor at any given point in the natural history of the disease.

16
UI - 12031865
AU - Pedley ID
TI - Transperineal interstitial permanent prostate brachytherapy for carcinoma of the prostate.
SO - Surg Oncol 2002 Jun;11(1-2):25-34
AD - Northern Centre for Cancer Treatment, Newcastle General Hospital, Westgate Road, Newcastle Upon Tyne NE4 6BE, UK. ian.pedley@nuth.northy.nhs.uk

17
UI - 10761263
AU - See A; Kron T; Johansen J; Hamilton C; Bydder SA; Hawkins J; Roff M;
TI - Denham JW Decision-making models in the analysis of portal films: a clinical pilot study.
SO - Australas Radiol 2000 Feb;44(1):72-83
AD - Department of Radiation Oncology, Newcastle Mater Misericordiae Hospital, Waratah, New South Wales, Australia.
Portal films continue to play an important role in the verification of radiotherapy treatment. There is still some discussion, however, as to what action should be taken after a port film has shown a radiation field deviation from the prescribed volume. It was the aim of the present pilot study to investigate the performance of three decision-making models ('Amsterdam', 'Quebec' and 'Newcastle') and an expert panel basing their decision on intuition rather than formal rules after portal film acquisition in a clinical setting. Portal films were acquired on every day during the first week of treatment for five head and neck and five prostate cancer patients (diagnostic phase). If required, the field position was modified according to our normal practice following the recommendation of the expert panel. In order to analyse the results of the models, however, additional port films were taken in the following 3 treatment weeks with the patient moved as required by the different models (intervention phase). The portal films were taken over 4 consecutive days, positioning the patient according to each of the different models on one day each. None of the models diagnosed a field misplacement in the head and neck patients, while the 'Amsterdam' and 'Quebec' models predicted a move in one prostate patient. The 'Newcastle' model, which is based on Hotelling's T2 statistic, proved to be more sensitive and diagnosed a systematic displacement for three prostate patients. The intervention phase confirmed the diagnosis of the model, even if the three portal films taken with the patient position adjusted as required by the model proved to be insufficient to demonstrate an improvement. The 'Newcastle' model does not rely on assumptions about the random movement of patients and requires five portal films before a decision can be reached. This approach lends itself well to incorporation into electronic portal imaging 'packages', where repeated image acquisitions present no logistical difficulty.

18
UI - 12136225
AU - Kim Y; Roscoe JA; Morrow GR
TI - The effects of information and negative affect on severity of side effects from radiation therapy for prostate cancer.
SO - Support Care Cancer 2002 Jul;10(5):416-21
AD - Mount Sinai School of Medicine, One Gustave Levy Place, Box 1130, New York, NY 10029-6574, USA. youngmee.kim@mssm.edu
A randomized clinical trial with 152 patients was conducted to examine the effects of an informational intervention on the severity of side effects resulting from radiation therapy for prostate cancer. We also examined negative affect both as a predictor and as an outcome variable. The informational intervention, given to patients at the first and fifth treatments, was based upon self-regulation theory and provided patients with specific, objective information about what to expect during their radiation treatments. Patients in the comparison group received general information at the same point in time. Negative affect was measured using the Profile of Mood States (POMS) prior to the intervention and at the last treatment. The severity of side effects for each individual was assessed at their last treatment. The results showed that patients in the informational intervention group reported significantly fewer problems with sleep and less fatigue (marginally significant) than those in the comparison group. Negative affect was not influenced by group assignment. Baseline negative affect was not related to symptom development, although the development of side effects was associated with an increase in negative mood. The results suggest that patients could benefit from increased knowledge about what to expect during their radiation treatments.

19
UI - 12237913
AU - Potters L; Purrazzella R; Brustein S; Fearn P; Leibel SA; Kattan MW
TI - A comprehensive and novel predictive modeling technique using detailed pathology factors in men with localized prostate carcinoma.
SO - Cancer 2002 Oct 1;95(7):1451-6
AD - Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center at Mercy Medical Center, Rockville Centre, New York 11570, USA. PottersL@mskcc.org
BACKGROUND: The purpose of the current study was to evaluate modeling strategies using sextant core prostate biopsy specimen data that would best predict biochemical control in patients with localized prostate carcinoma treated with permanent prostate brachytherapy (PPB). METHODS: One thousand four hundred seventy-seven patients underwent PPB between 1992 and 2000. The authors restricted analysis to those patients who had sextant biopsies (n = 1073). A central pathology review was undertaken on all specimens. Treatment consisted of PPB with either I-125 or Pd-103 prescribed to 144 Gy or 140 Gy, respectively. Two hundred twenty-eight patients (21%) received PPB in combination with external radiotherapy and 333 patients (31%) received neoadjuvant hormones. In addition to clinical stage, biopsy Gleason sum, and pretreatment prostate specific antigen (pretx-PSA), the following detailed biopsy variables were considered: mean percentage of cancer in an involved core; maximum percentage of cancer; mean primary and secondary Gleason grades; maximum Gleason grade (primary or secondary); percentage of cancer in the apex, mid, and base; percent of cores positive; maximum primary and secondary Gleason grades in apex, mid, and base; maximum percent cancer in apex, mid, and base; maximum Gleason grade in apex, mid, and base; maximum primary Gleason grade; and maximum secondary Gleason grade. In all, 23 biopsy variables were considered. Four modeling strategies were compared. As a base model, the authors considered the pretx-PSA, clinical stage, and biopsy Gleason sum as predictors. For the second model, the authors added percent of cores positive. The third modeling strategy was to use stepwise variable selection to select only those variables (from the total pool of 26) that were statistically significant. The fourth strategy was to apply principal components analysis, which has theoretical advantages over the other strategies. Principal components analysis creates component scores that account for maximum variance in the predictors. RESULTS: The median followup of the study cohort was 36 months (range, 6-92), and the Kattan modification of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition was used to define PSA freedom from recurrence (PSA-FFR). The four models were compared in their ability to predict PSA-FFR as measured by the Somers D rank correlation coefficient. The Somers D rank correlation coefficients were then corrected for optimism with use of bootstrapping. The results for the four models were 0.32, 0.34, 0.37, and 0.39, respectively. CONCLUSIONS: The current study shows that the use of principal components analysis with additional pathology data is a more discriminating model in predicting outcome in prostate carcinoma than other conventional methods and can also be used to model outcome predictions for patients treated with radical prostatectomy and external beam. Copyright 2002 American Cancer Society.DOI 10.1002/cncr.10869

20
UI - 12002354
AU - Aus G; Adolfsson J; Selli C; Widmark A
TI - Treatment of patients with clinical T3 prostate cancer.
SO - Scand J Urol Nephrol 2002 Feb;36(1):28-33
AD - Department of Urology, Ryhov Hospital, Jonkoping, Sweden. gunnar.aus@ryhov.ltjkpg.se
OBJECTIVE: To describe and evaluate treatment alternatives for patients with clinical T3 prostate cancer. MATERIAL AND METHODS: Literature review with main focus on recent studies in order to include the impact of prostate specific antigen (PSA). The possibility of using neoadjuvant/adjuvant hormonal therapy in combination with surgery or radiation was assessed. Results were related to life expectancy, tumour grade and serum PSA. RESULTS: M and N-staging is mandatory before treatment with curative intent. Watchful waiting is an option for selected patients but early hormonal therapy seems to offer some survival advantages. Standard 65-70Gy external beam radiation is not sufficient for these patients with extracapsular disease but better results are obtained with dose-escalation (beyond 70Gy) and/or adjuvant hormonal therapy. Radical prostatectomy may be an option for patients with long life expectancy and "early" tumours, neoadjuvant hormonal withdrawal is of no proven value. CONCLUSIONS: Patients with a long life expectancy should not be denied treatment with curative intent solely based on the finding of extracapsular disease.

21
UI - 12002355
AU - Fossa SD; Vaage S; Letocha H; Iversen J; Risberg T; Johannessen DC; Paus
TI - E; Smedsrud T; Norwegian Urological Cancer Group Liposomal doxorubicin (Caelyx) in symptomatic androgen-independent prostate cancer (AIPC)--delayed response and flare phenomenon should be considered.
SO - Scand J Urol Nephrol 2002 Feb;36(1):34-9
AD - Department of Medical Oncology and Radiotherapy, The Norwegian Radium Hospital, Montebello, Oslo. s.d.fossa@klinmed.uio.no
BACKGROUND: Compared with the native drug, liposomal PEG-coated doxorubicin (Caelyx) enhances tumour activity and reduces toxicity. The formulation may therefore be beneficial in anthracycline-sensitive malignancies, where toxicity represents a major problem, as is the case in androgen-insensitive prostate cancer (AIPC). METHODS: In a multi-centre design 28 patients with advanced AIPC received Caelyx 40 mg/m2 as a 1-hour infusion every month. PSA-based biochemical and subjective response was recorded. RESULTS: Three patients had biochemical responses, a subjective response was recorded in a fourth patient. No Grade 4 toxicity was encountered. Three patients developed a spontaneously recovering plantar-palmar erythema. In 3 of the 4 responding patients, the nadir PSA value was noted after 12 and 16 weeks, respectively. A possible flare phenomenon for PSA was evident in 4 patients. CONCLUSION: Caelyx has limited activity in advanced AIPC. Due to its low toxicity profile the drug may be a worthwhile component of combination treatment of this chemotherapy-resistant condition. In general, clinicians should be aware of possible delay in PSA response as well as possible flare phenomenon during investigational systemic treatment of AIPC. Furthermore, standardization of blood sampling and PSA analyses are necessary in future therapeutic trials of AIPC.

22
UI - 12199018
AU - Scobie B
TI - Cancer flourishes.
SO - N Z Med J 2002 Jun 21;115(1156):304

23
UI - 12230706
AU - Michaelson D; Talcott J; Smith M
TI - Prostate cancer: metastatic.
SO - Clin Evid 2002 Jun;(7):804-11
AD - Massachusetts General Hosptial, Boston, USA.

24
UI - 12230707
AU - Wilt T
TI - Prostate cancer: non-metastatic.
SO - Clin Evid 2002 Jun;(7):812-23
AD - VA Coordinating Center for the Cochrane Review Group in Prostate Diseases, Urologic Malignancies and the Center for Chronic Diseases Outcomes Research, Minneapolis VA Hospital, Minneapolis, USA.

26
UI - 11978173
AU - de Lemos ML
TI - Herbal supplement PC-Spes for prostate cancer.
SO - Ann Pharmacother 2002 May;36(5):921-6
AD - Provincial Systemic Therapy Program, British Columbia Cancer Agency, 600 W. 10th Ave., Vancouver V5Z 4E6, British Columbia, Canada. mdelemos@bccancer.bc.ca
OBJECTIVE: To determine the efficacy and toxicity of the herbal supplement PC-Spes in prostate cancer patients. METHODS: Literature the Annual Meeting of the American Society of Clinical Oncology (1995-2001). RESULTS: PC-Spes was associated with biochemical and clinical response in some prostate cancer patients. The mechanisms of action of PC-Spes appeared to be related to its estrogenic activity. CONCLUSIONS: PC-Spes is associated with some efficacy in prostate cancer patients. Due to the limited data available, it should not be used to replace standard androgen suppression therapy in androgen-dependent patients. PC-Spes may have a role for patients who have failed standard treatments for androgen-independent disease and have no history of thromboembolism or abnormal bleeding. PC-Spes has a toxicity profile similar to those of androgen suppression and estrogen therapy.

27
UI - 12185298
AU - Goodin S; Rao KV; DiPaola RS
TI - State-of-the-art treatment of metastatic hormone-refractory prostate cancer.
SO - Oncologist 2002;7(4):360-70
AD - The Cancer Institute of New Jersey, New Brunswick, New Jersey 08901, USA.
Initial therapy for advanced prostate cancer includes androgen ablation by surgical or medical castration. Still, nearly all men with metastases will progress to hormone-refractory prostate cancer (HRPC). Current U.S. Food and Drug Administration-approved agents for the treatment of HRPC include mitoxantrone and estramustine, although the vinca alkaloids and the taxanes have shown promising activity in single-agent phase II trials. Combinations of these agents induce a biochemical response in greater than 50% of patients, but the median duration of response is approximately 6 months. Overall survival of patients treated with these combinations is approximately 18-24 months. Studies are ongoing to develop novel therapies that target specific molecular pathways or mechanisms of chemotherapy resistance. Novel agents under development include growth factor receptor inhibitors, antisense oligonucleotides, bisphosphonates, and cell differentiating agents. Evaluation and incorporation of these agents into existing treatment regimens will guide us in the development of more active regimens in the treatment of HRPC.

28
UI - 12228757
AU - Patterson SG; Balducci L; Pow-Sang JM
TI - Controversies surrounding androgen deprivation for prostate cancer.
SO - Cancer Control 2002 Jul-Aug;9(4):315-25
AD - Genitourinary Oncology Program, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL 33612, USA. pattersg@moffitt.usf.edu
BACKGROUND: Management of metastatic prostate cancer continues to evolve. The widespread use of the prostate-specific antigen (PSA) assay has led to earlier diagnosis and earlier detection of recurrent disease. Debates continue regarding the proper use and timing of endocrine therapy with orchiectomy, estrogen agonists, luteinizing hormone-releasing hormone (LHRH) analogs, LHRH antagonists, and androgen antagonists. METHODS: The authors reviewed the significant published materials of the last 20 years that have shaped hormonal management of metastatic and progressive prostate cancer. Major areas of controversy were also identified. RESULTS: The present approach to hormonal management is summarized. Five potential pathways to the development of androgen-independent prostate cancer are described. Controversial topics of hormonal management, including immediate vs delayed hormonal therapy, monotherapy vs maximal androgen blockade (MAB), and intermittent hormonal therapy, are discussed. CONCLUSIONS: Orchiectomy, estrogen agonists, and LHRH analogs have therapeutic equivalence. Patients who have a rising PSA after definitive treatment for prostate cancer and high risk of recurrent disease may warrant early androgen deprivation. MAB does not appear to be significantly better than single-agent LHRH analog therapy. Intermittent therapy may delay emergence of androgen independence and maintain or improve quality of life.

29
UI - 12352408
AU - Gretzer MB; Trock BJ; Han M; Walsh PC
TI - A critical analysis of the interpretation of biochemical failure in surgically treated patients using the American Society for Therapeutic Radiation and Oncology criteria.
SO - J Urol 2002 Oct;168(4 Pt 1):1419-22
AD - The James Buchanan Brady Urological Institute, The Johns Hopkins University Medical Institutions, Baltimore, Maryland, USA.
PURPOSE: The use of prostate specific antigen (PSA) to indicate biochemical failure has become an accepted procedure to measure the effectiveness of therapy. Because long-term randomized studies comparing radiation modalities to radical prostatectomy are not available, use of biochemical recurrence as a surrogate measure of efficacy is increasing. Unfortunately, the definition of failure is not uniform among therapies. We evaluate how the American Society for Therapeutic Radiation and Oncology (ASTRO) criteria affect the interpretation of failure when applied to radical prostatectomy. MATERIALS AND METHODS: We retrospectively reviewed data from 2,691 men who underwent anatomical radical prostatectomy for localized disease between 1985 and 2000. All patients had regular followup visits ranging from 6 months to 15 years (mean 6). No patients were treated with radiation or hormonal therapy preoperatively or postoperatively until clinical recurrence. Biochemical failure was defined as any measurable PSA 0.2 ng./ml. or greater. We evaluated how elements of the ASTRO criteria affected the failure rate when applied to this series. We looked at 1) backdating the failure date to the midpoint between nadir and first PSA greater than 0.2 ng./ml., 2) early censoring if only 1 or 2 increasing values were available and 3) defining failure after 3 consecutive PSA increases and backdating failure time (midpoint of nadir and first PSA increase). RESULTS: Using actuarial analysis of the data defining failure as the first PSA 0.2 ng./ml. or greater, biochemical freedom from failure at 5, 10 and 15 years was 85%, 77% and 68%, respectively. In contrast, when backdating was used in this series, almost all failures occurred early with rare late failures (freedom from failure 82%, 80% and 80% at 5, 10 and 15 years, respectively). The difference in failure became even more pronounced when ASTRO criteria were applied requiring 3 consecutive increases, and backdating failure to the midpoint between nadir and first PSA (freedom from failure 90%, 90% and 90% at 5, 10 and 15 years, respectively). CONCLUSIONS: The application of ASTRO criteria to a mature series of surgically treated patients with localized prostate cancer produced an apparent improvement in the probability of being biochemically free of disease at 15 years from 68% to 90%. Until prospective trials comparing these different therapies become available, caution should be exercised when interpreting outcomes between series due to the inherent differences in definition of biochemical failure.

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