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Abramson Cancer CenterNCI CANCERLIT® Search: Therapy of Prostate Cancer - April 2002
National Cancer Institute®
Last Modified: April 1, 2002
Table of Contents
1
UI - 11851629
AU - Reid-Pitts W Jr
TI -
Prostatic intraepithelial neoplasia and putative precursor lesions of
prostate cancer: a clinical perspective.
SO - BJU Int 2001 Dec;88(9):985-6
2
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.
3
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.
4
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. ccparker@doctor.org.uk
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
5
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.
6
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
7
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.
mercedes.salido@uca.es
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.
8
UI - 11904307
AU - Talcott JA
TI -
Androgen deprivation as primary treatment for early prostate cancer:
should we "just do something"?
SO - J Natl Cancer Inst 2002 Mar 20;94(6):407-9
9
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.
10
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.
11
UI - 11902534
AU - Howe M
TI -
National prostate tumour bank launched in Australia.
SO - Lancet Oncol 2001 Nov;2(11):656
12
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
13
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.
14
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.
15
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. mishel@email.unc.edu
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.
16
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.
17
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. sinibvi@jhmi.edu
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.
18
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.
dipaolrs@umdnj.edu
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.
19
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.
20
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.
21
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. moyad@umich.edu
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.
22
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.
lotem@isdn.net.il
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.
23
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.
24
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.
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