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Peter E Clark

Publications and source records attributed to Peter E Clark.

At least 19 recordsLinked to original sources
PubMed2006

Vinorelbine, doxorubicin, and prednisone in androgen-independent prostate cancer.

BACKGROUND: Ultimately, patients with metastatic prostate cancer progress on androgen ablation therapy. The investigation of new chemotherapeutic regimens for the treatment of androgen-independent prostate cancer (AIPC) is essential. The authors conducted a Phase II trial with vinorelbine, doxorubicin, and daily prednisone (NAP) to investigate the antitumor activity and palliative response of this regimen in patients with AIPC. METHODS: Forty-six patients entered this Phase II combination chemotherapy trial. Patients were treated with both vinorelbine and doxorubicin at doses of 20 mg/m2 on Days 1, 8, and 15 every 28 days and prednisone 5 mg twice daily. Endpoints included prostate-specific antigen (PSA) response and palliation, as measured by the Functional Assessment of Cancer Therapy-Prostate (FACT-P) instrument, the Brief Pain Inventory Scale, and a narcotic analgesic log. RESULTS: The median follow-up for all 46 patients was 13.4 months. Fifty-two percent of patients had impaired performance status at baseline. One responding patient remained on NAP and was progression-free at 11.5 months. Thirty-nine patients progressed, 3 patients died prior to response assessment, and 3 patients refused therapy. The median overall survival was 57 weeks (95% confidence interval [95% CI], 36-76 weeks), and the median time to disease progression was 17 weeks (range, 11-24 weeks). The PSA response among the 36 patients who completed 3 cycles of NAP was 42% (95% CI, 26-59%). There was a statistically significant improvement in quality of life measured both by the FACT-General instrument (P = .03) and the FACT-P instrument (P = .0006) over the 3 months compared with baseline measurements. Pain medicine use also improved: The median morphine equivalents among patients who were taking pain medications at the time of study enrollment showed a substantial decline after 1 cycle of treatment that was maintained. Pain (as assessed by the Brief Pain Inventory) improved compared with baseline pain at the 2nd-month assessment (worst pain, P = .08; least pain, P = .02; and average pain, P = .003). Overall, the regimen was tolerated well. The most common side effects were mild fatigue and gastrointestinal complaints (all of which were Grade 1 or 2 [according to Version 2.0 of the Expanded Common Toxicity Criteria]). Seventeen patients (37%) experienced Grade 3 or 4 neutropenia. Five patients (11%) developed a cardiac ejection fraction of <50% during treatment and had doxorubicin discontinued. No patients developed clinical congestive heart failure. CONCLUSIONS: The NAP combination produced substantive palliation and a moderate response rate in men with AIPC.

Aged↗
PubMed2006

Complementary and alternative medicine for advanced prostate cancer.

Complimentary and alternative medicines (CAM) have increased drastically in popularity in the past decade. These are largely in the form of nutritional supplements. Despite a wealth of information sources on the subject, the fundamental problem with CAM therapies is a dearth of evidence-based medicine. Advanced prostate cancer has significant long-term morbidity, and there is a growing interest in alternative and complimentary forms of therapy that will improve the outcomes of patients who have recurrent or advanced prostate cancer while obviating the need for more toxic forms of therapy. In this article we summarize the use of some of the more common CAM nutritional supplements and review the scientific data that are available to support their use.

Antioxidants↗
PubMed2006

Percentage of positive biopsies associated with freedom from biochemical recurrence after low-dose-rate prostate brachytherapy alone for clinically localized prostate cancer.

OBJECTIVES: To examine the relationship between the percentage of positive biopsies (PPBs) and freedom from biochemical recurrence (FFBR) in men treated with low-dose-rate prostate brachytherapy (LDRPB) alone. The PPBs has been associated with FFBR in men treated with radical prostatectomy and external beam radiotherapy for prostate cancer. METHODS: This report concerns 108 men treated with LDRPB alone between November 1997 and December 1999. All patients had clinically localized prostate cancer confirmed by biopsy. All men were treated with iodine-125 to 144 Gy. FFBR was estimated using the product-limit method. Putative covariates for FFBR, including T stage, Gleason score, pretreatment prostate-specific antigen level, minimal dose received by 90% of the target volume, and PPBs, were examined using the proportional hazards regression model. RESULTS: The median follow-up was 61 months. Of the 108 men, 13 developed evidence of biochemical relapse at a median of 25 months. The 5-year estimate of FFBR was 87% (95% confidence interval 81% to 93%) for the entire cohort. On univariate analysis, prostate-specific antigen, T stage, minimal dose received by 90% of the target volume, and PPBs were associated with FFBR. In the multivariate model, the PPBs was the only variable that predicted for FFBR (P = 0.002). The 5-year estimate of FFBR was 95% for patients with less than 50% PPB disease versus 63% in patients with more than 50% PPB disease (P < 0.0001). CONCLUSIONS: The PPBs is an important independent predictor of FFBR after LDRPB alone. The FFBR after LDRPB in the group of patients with more than 50% PPBs was poor.

Aged↗
PubMed2006

Phase I-II prospective dose-escalating trial of lycopene in patients with biochemical relapse of prostate cancer after definitive local therapy.

OBJECTIVES: To report a prospective trial of lycopene supplementation in biochemically relapsed prostate cancer. METHODS: A total of 36 men with biochemically relapsed prostate cancer were enrolled in a dose-escalating, Phase I-II trial of lycopene supplementation. Six consecutive cohorts of 6 patients each received daily supplementation with 15, 30, 45, 60, 90, and 120 mg/day for 1 year. The serum levels of prostate-specific antigen (PSA) and plasma levels of lycopene were measured at baseline and every 3 months. The primary endpoints were PSA response (defined as a 50% decrease in serum PSA from baseline), pharmacokinetics, and the toxicity/tolerability of this regimen. RESULTS: A total of 36 patients were enrolled. The median age was 74 years (range 56 to 83), with a median serum PSA at entry of 4.4 ng/mL (range 0.8 to 24.9). No serum PSA responses were observed, and 37% of patients had PSA progression. The median time to progression was not reached. Toxicity was mild, with 1 patient discontinuing therapy because of diarrhea. Significant elevations of plasma lycopene were noted at 3 months and then appeared to plateau for all six dose levels. The plasma levels for doses between 15 and 90 mg/day were similar, with additional elevation only at 120 mg/day. CONCLUSIONS: Lycopene supplementation in men with biochemically relapsed prostate cancer is safe and well tolerated. The plasma levels of lycopene were similar for a wide dose range (15 to 90 mg/day) and plateaued by 3 months. Lycopene supplementation at the doses used in this study did not result in any discernible response in serum PSA.

Adenocarcinoma↗
PubMed2006

Bladder cancer.

PURPOSE OF REVIEW: This article will review the diagnosis and management of bladder cancer at each stage, from superficial to metastatic disease with an emphasis on recent developments over the last year. RECENT FINDINGS: Bacille Calmette-Guerin is the most effective therapy for carcinoma in situ. All patients who receive intravesical therapy with bacille Calmette-Guerin should be considered for ongoing maintenance therapy. The management of muscle invasive disease in the United States centers on radical cystectomy with bilateral pelvic lymphadenectomy. Areas of research include the optimal role for bladder preservation therapy, a growing experience in centers with laparoscopy, the effect of urinary diversion on quality of life, and the optimal standard for pelvic lymphadenectomy at surgery. The role of combination chemotherapy for advanced bladder cancer continues to evolve. Many questions remain unanswered including the relative value of neoadjuvant versus adjuvant chemotherapy for locally advanced disease and optimal chemotherapy regimen. SUMMARY: The detection of bladder cancer continues to rely on direct visualization with cystoscopy. Efforts are underway to improve the utility of urinary markers and cystoscopy through fluorescence endoscopy. The management of superficial bladder cancer is based on transurethral resection of the tumor with perioperative intravesical instillation of chemotherapy strongly suggested for most patients. Risk stratifying patients with high-risk superficial bladder cancer remain a challenge and area of future research.

Administration, Intravesical↗
PubMed2005

DNA damage levels in prostate cancer cases and controls.

This study used the alkaline Comet assay to evaluate whether basal or H2O2-induced DNA damage is associated with prostate cancer (CaP) risk. Using lymphocyte samples from 158 CaP cases and 128 controls, collected in an ongoing case-control study, our results showed that basal DNA damage did not differ between cases and controls. However, the H2O2-induced DNA damage level was significantly higher in incident cases (mean +/- SD; 6.61 +/- 4.43, n = 102) than controls (5.30 +/- 3.60, n = 128) or prevalent cases (4.47 +/- 3.19; n = 56). Incident cases with a positive smoking history had significantly higher H2O2-induced DNA damage than never-smokers (7.57 +/- 4.82 versus 4.52 +/- 2.40; P < 0.001). Above-median H2O2-induced DNA damage was associated with a 1.61-fold increase in CaP risk [95% confidence interval (CI) = 0.92-2.81], after adjustment for age, race, benign prostatic hyperplasia (BPH), smoking history and family history (FH). Using the lowest quartile of H2O2-induced DNA damage as the referent group, the adjusted ORs for the 25th, 50th and 75th quartiles were 0.90 (95% CI = 0.39-2.05), 1.06 (95% CI = 0.48-2.35) and 2.05 (95% CI = 0.96-4.37), respectively (P = 0.046, test for linear trend). The association between CaP and DNA damage was modified by age, smoking history, family history and body mass index. Our results suggest that DNA damage may be associated with CaP risk. However, larger case-control and follow-up studies are warranted to further evaluate the potential application of the alkaline Comet assay in CaP risk assessment and prevention.

Age Factors↗
PubMed2005

Radical cystectomy in the elderly: comparison of clincal outcomes between younger and older patients.

BACKGROUND: The authors report their experience with radical cystectomy for transitional cell carcinoma (TCC) of the bladder comparing clinical outcomes, including complication rates, among older patients versus younger patients in a high-volume center specializing in the treatment of patients with advanced carcinoma of the urinary bladder. METHODS: A retrospective review was undertaken of 1054 patients who underwent radical cystectomy for bladder TCC from 1971 through 1997. Four age groups were compared; < 60 years at the time of cystectomy (n = 309 patients), age 60-69 years (n = 381 patients), age 70-79 years (n = 314 patients), and age > or = 80 years (n = 50 patients). RESULTS: The median length of hospital stay in patients ages < 60 years, 60-69 years, 70-79 years, and > or = 80 years was 10 days, 10 days, 11 days, and 11 days, respectively (P < 0.001). The corresponding rates of overall early complications were 24%, 25%, 37%, and 30%, respectively (P = 0.002); whereas the corresponding late complication rates were 36%, 30%, 22%, and 14%, respectively (P < 0.001). The rate of early diversion-related complications did not differ significantly (11%, 8%, 12%, and 6%, respectively; P = 0.14). The operative mortality rates were 1%, 3%, 4%, and 0%, respectively (P = 0.14). There was no difference with respect to early complications, early diversion-related complications, late complications, or operative mortality comparing patients age > 70 years who underwent ileal conduit versus orthotopic urinary diversion (P = 0.20, P = 0.61, P = 0.53, and P = 0.78, respectively). CONCLUSIONS: Elderly patients who underwent cystectomy for TCC had similar mortality and early diversion-related complication rates. Carefully selected elderly patients safely can be offered an orthotopic urinary diversion. Chronological age, per se, is not a contraindication for radical cystectomy in the setting of invasive bladder carcinoma.

Age Factors↗
PubMed2005

Radical cystectomy in the elderly: Comparison of survival between younger and older patients.

BACKGROUND: The authors reported their experience with radical cystectomy for transitional cell carcinoma (TCC) of the bladder. They compared pathologic features and survival rates between older and younger patients. METHODS: The authors retrospectively reviewed the records of 1054 patients who underwent radical cystectomy for bladder TCC between 1971 and 1997. Four age groups were compared: < 60 years old at the time of cystectomy (n = 310), 60-69 years old (n = 381), 70-79 years old (n = 313), and >/= 80 years old (n = 50). RESULTS: There were no significant differences in pathologic features among the groups regarding frequency of carcinoma in situ, high-grade disease, p53 status, and lymph node positivity. However, in the age groups < 60, 60-69, 70-79, and >/= 80, 45%, 49%, 51%, and 72% of patients, respectively, had extravesical TCC (P=0.004). Significant differences also were seen in the proportion of patients who received adjuvant chemotherapy (26%, 26%, 15%, and 6%, respectively; P < 0.001). The 5-year overall survival rates for patients < 60, 60-69, 70-79, and >/= 80 years old were 72%, 58%, 54%, and 33%, respectively (P < 0.001). The 5-year disease recurrence-free survival rates were 75%, 65%, 68%, and 45%, respectively (P = 0.003). The elderly had a lower probability of receiving adjuvant chemotherapy. CONCLUSIONS: Elderly patients undergoing cystectomy for TCC had similar pathologic features (except for disease stage) as younger patients. In the current series, elderly patients undergoing cystectomy had a higher pathologic stage and were less likely to receive adjuvant chemotherapy. The elderly had worse disease recurrence-free survival rates. Further work is needed to identify the causes for this and to develop strategies to improve cancer control in elderly patients.

Age Factors↗
PubMed2005

Dosimetric quantifiers for low-dose-rate prostate brachytherapy: is V(100) superior to D(90)?

PURPOSE: The purpose of the present report is to describe the relationship between two dosimetric quantifiers (V(100) and D(90)) and freedom from biochemical recurrence (FFBR) in a cohort of men treated with low-dose-rate prostate brachytherapy (LDRPB) alone. METHODS AND MATERIALS: One hundred three men were treated with LDRPB alone between September 1997 and December 1999. All men had histologically confirmed clinically localized prostate cancer. Fifty-nine percent of the cohort had low-risk disease (defined as PSA<10, Gleason <7, and T stage /=10, Gleason>/=7, or T stage T2b). The prescription dose was 144Gy according to the Task Group 43 formalism. LDRPB was performed jointly by a radiation oncologist and a urologist. Dosimetric quantifiers (D(90), V(100)) were calculated from a CT scan performed 1 month after LDRPB. Biochemical recurrence was defined according to the ASTRO Consensus Definition. FFBR was estimated using the product-limit method. Disease-specific and treatment variables were examined as putative covariates for FFBR using the proportional hazards regression method. Univariate and multivariate methods were used. All p values are two sided. RESULTS: The median followup for the entire cohort is 61 months. The median followup of patients at risk for biochemical failure is 66 months. The median D(90) is 129Gy (range 47-221Gy), and the median V(100) is 86% (range 51-99%). Thirteen men have developed evidence of biochemical relapse at a median of 25 months (range 6-42 months). The 5-year estimate of FFBR for the entire cohort is 87% (95% CI 80-94%). On univariate analysis, disease-specific variables found to be significantly associated with FFBR included pretreatment PSA and percent positive biopsies. When considered as a continuous variable, each of the dosimetric quantifiers was associated with FFBR (V(100): p=0.007; D(90): p=0.05). D'Amico risk group classification is highly predictive of FFBR after LDRPB (HR 5.68, p=0.003). Multivariate analysis indicated that each dosimetric quantifier was independently associated with FFBR, but due to the high degree of correlation (Pearson correlation coefficient 0.94, p<0.0001) between the dosimetric quantifiers both could not be included simultaneously in the model. In the two models explored, V(100) was at least as good as D(90) in predicting FFBR. CONCLUSIONS: Dosimetric quantifiers (V(100) and D(90)) are independent predictors of FFBR after treatment with LDRPB alone. In our experience, V(100) seems to be at least equivalent (and perhaps superior) to D(90) for predicting FFBR.

Aged↗
PubMed2005

Contemporary management of the urethra in patients after radical cystectomy for bladder cancer.

The incidence of urethral TCC after radical cystectomy is approximately 8% overall. The most important risk factor for urethral TCC after radical cystectomy and urinary diversion is prostatic involvement by TCC, particularly stromal invasion. The safety of using the urethra for orthotopic urinary diversion seems to be best when intra-operative frozen section analysis of the urethral margin is performed at the time of radical cystectomy. There is provocative but unconfirmed evidence that orthotopic urinary diversion may be protective against the development of urethral TCC. Although most urethral "recurrences" occur within 5 years, delayed recurrences have been documented, mandating life-long follow-up of the retained urethra. Follow-up should include urinary cytology, either voided or urethral wash cytology as appropriate, with evaluation by endoscopy of any urethral related symptoms or change in voiding symptoms. The management of urethral TCC after cystectomy remains a total urethrectomy including excision of the meatus; however, in carefully selected patients with superficial disease and an orthotopic urinary diversion, urethra sparing may be attempted after a careful discussion with the patient. Survival after urethral TCC has generally been disappointing. The relative value of urethral versus original cystectomy pathologic stage and symptomatic versus nonsymptomatic recurrence in predicting survival remains controversial and awaits further studies that will most likely require the pooling of data from several large series.

Carcinoma, Transitional Cell↗
PubMed2005

Inflammatory myofibroblastic tumor associated with renal cell carcinoma.

A 46-year-old man was referred for evaluation of a 13-cm renal mass. Right radical nephrectomy was performed. Pathologic evaluation revealed inflammatory myofibroblastic tumor (IMT) and renal cell carcinoma. To our knowledge, only 28 cases of IMT associated with the kidney have been reported in published studies. This is the first reported case of IMT associated with malignancy in the urogenital tract. Some investigators have suggested that biopsy-proven IMT can be managed conservatively, but the findings of this report have demonstrated the need for radical nephrectomy in this patient population to rule out associated malignancy.

Carcinoma, Renal Cell↗
PubMed2005

Bladder cancer.

PURPOSE OF REVIEW: This article reviews the recent literature concerning important issues in the management of patients with bladder cancer. A brief overview of all aspects of bladder cancer including the etiology, diagnosis, and treatment are discussed with a focus on recent advances. RECENT FINDINGS: Bladder cancer is a significant cause of morbidity and mortality. The treatment for bladder cancer should be based on individual patient risk assessment and should include a multidisciplinary approach. In patients with superficial bladder cancer, research has focused on improving and optimizing intravesical therapy to reduce tumor recurrence and progression as well as on methods to better select the most appropriate treatment for patients with high-risk features. The important prognostic and therapeutic role of lymphadenectomy during radical cystectomy has become apparent and recent work has attempted to better define what should be considered the standard for lymph node dissection. Finally, in an attempt to improve survival, advances have been made using systemic chemotherapy in both the perioperative settings as well as for treatment of metastatic bladder cancer. SUMMARY: Research continues to improve our understanding of bladder cancer. This ongoing investigation is currently being translated to the bedside with refinements in the diagnosis and treatment of patients with bladder cancer.

Cystectomy↗
PubMed2005

Recent advances in the treatment of bladder cancer.

Bladder cancer continues to provide urologists and researchers with a clinical and scientific challenge. Several urinary markers used in the detection and screening of patients with bladder cancer are currently under investigation. Improvements in intravesical therapy are proving to help decrease both tumor recurrence and progression in patients with high-risk disease. In patients with organ-confined, node-negative bladder cancer, radical cystectomy provides excellent local control and long-term disease-free survival. The use of an extended lymphadenectomy at the time of cystectomy may yield improved prognostic information as well as a potential survival benefit. Neoadjuvant chemotherapy and less toxic combination chemotherapy regimens are offering potential improvements in patients with extravesical or nodal extension. The current methods of detection, as well as available therapeutic treatment options are reviewed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2004

The ADPRT V762A genetic variant contributes to prostate cancer susceptibility and deficient enzyme function.

The ADP-ribosyltransferase (ADPRT) gene encodes a zinc-finger DNA-binding protein, poly(ADP-ribose) polymerase-1 (PARP-1), that modifies various nuclear proteins by poly(ADP-ribosyl)ation and functions as a key enzyme in the base excision repair pathway. We have conducted two studies to test whether an amino acid substitution variant, ADPRT V762A (T2444C), is associated with prostate cancer (CaP) risk and decreased enzyme function. The first study used genomic DNA samples from an ongoing, clinic-based case-control study (488 cases and 524 controls) to show that a higher percentage of the CaP cases carried the ADPRT 762 AA genotype than controls (4% versus 2%). In Caucasians, the AA genotype was significantly associated with increased CaP risk [odds ratio (OR), 2.65; 95% confidence interval (CI), 1.08-6.49], and the VA genotype was associated with a slight but not significantly increased CaP risk (OR, 1.18; 95% CI, 0.85-1.64) using VV as the referent group after adjustment for age, benign prostatic hyperplasia, and family history. Furthermore, this association was stronger in younger (<65) men (OR, 4.77; 95% CI, 1.01-22.44) than older (> or =65) men (OR, 1.78; 95% CI, 0.55-5.82). The second study used freshly isolated peripheral lymphocytes from 354 cancer-free subjects to demonstrate that the ADPRT 762 A allele contributed to significantly lower adenosine diphosphate ribosyl transferase (ADPRT)/PARP-1 activities in response to H2O2 in a gene dosage-dependent manner (P < 0.0001, test for linear trend). The PARP-1 activities (mean +/- SD dpm/10(6) cells) were 18,554 +/- 9,070 (n=257), 14,847 +/- 7,082 (n=86), and 12,155 +/- 6,334 (n=11) for VV, VA, and AA genotypes, respectively. This study is the first to provide evidence that the ADPRT V762A-genetic variant contributes to CaP susceptibility and altered ADPRT/PARP-1 enzyme function in response to oxidative damage.

ADP Ribose Transferases↗
PubMed2004

Radiofrequency ablation of renal tumors.

Radiofrequency ablation (RFA) of renal tumors is a relatively new treatment modality in the armamentarium of urologic surgeons. One of the challenges of this technique is attaining a zone of tissue destruction sufficient enough to kill the targeted tumor. Technologic innovations have aided in this effort. The clinical experience with RFA of renal tumors suggests that small, exophytic tumors may be more readily ablated. Although there is much optimism with regard to this technology, further study is required to better define the oncologic efficacy and refine proper patient selection.

Carcinoma, Renal Cell↗
PubMed2004

Phase II trial of combination interferon-alpha and thalidomide as first-line therapy in metastatic renal cell carcinoma.

OBJECTIVES: To present the results of a Phase II trial of thalidomide and interferon-alpha in renal cell carcinoma. METHODS: Patients with metastatic clear cell renal cell carcinoma and no prior systemic therapy were accrued. Interferon-alpha was administered at 5 million units subcutaneously three times per week. Thalidomide was started at 100 mg/day for 2 weeks and then escalated 200 mg every 2 weeks to 1000 mg or until grade 3-4 toxicity developed. Patients were assessed radiographically at baseline and after 12 weeks. Steady-state thalidomide plasma concentrations were determined. RESULTS: Thirty patients were enrolled. The median age was 62 years. Seventeen patients (57%) had undergone nephrectomy before therapy. One patient died during therapy. Of the 30 patients, 29 had at least grade 2 toxicity and 17 patients had at least grade 3. At 12 weeks, no patient had a complete response, 2 had a partial response (6.7%), 8 had stable disease (26.7%), and 11 (including 1 patient with an initial partial response) had disease progression (36.7%). Nine patients were removed from the study before 12 weeks. The median follow-up was 49.6 weeks (range 2.4 to 123.7). The median time of participation in the study was 11.1 weeks (range 1.4 to 63.9). At last follow-up, 2 patients were receiving the study therapy, 1 with stable disease at 64 weeks and 1 with a partial response at 53 weeks. The median survival was 68 weeks. A linear relationship was found between the thalidomide plasma concentration and dose. No relationship was apparent between the concentration and either treatment-related toxicity or response. CONCLUSIONS: Interferon-alpha and thalidomide as front-line therapy for metastatic renal cell carcinoma showed limited activity. The objective response rate was 7%. One third of patients experienced toxicity that required discontinuation of thalidomide. Randomized controlled studies are needed to determine any objective benefit of this regimen over either drug alone.

Adult↗