Biomedical subjects

M Craig Hall

Publications and source records attributed to M Craig Hall.

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

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↗

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

Phase I/II study of 19-nor-1alpha-25-dihydroxyvitamin D2 (paricalcitol) in advanced, androgen-insensitive prostate cancer.

PURPOSE: We assessed the safety and efficacy of the vitamin D analogue, 19-nor-1alpha-25-dihydroxyvitamin D2 (paricalcitol), in patients with androgen-independent prostate cancer. EXPERIMENTAL DESIGN: Patients received paricalcitol i.v. three times per week on an escalating dose of 5 to 25 microg (3-15 microg/m2). The primary end point was prostate-specific antigen (PSA) response. Secondary end points were characterization of toxicity in this population, changes in serum parathyroid hormone (PTH), and survival. RESULTS: A total of 18 patients were enrolled. No patient showed a sustained 50% drop in serum PSA, despite several large declines in PSA (e.g., 1,300 ng/mL). Paricalcitol was well tolerated. One instance of significant hypercalcemia, a serum calcium of 14.3 mg/dL, was observed at the highest dose (25 microg). At entry into the study, seven (41%) of the patients had elevated serum levels of PTH, which were significantly reduced by paricalcitol. Higher levels of serum PTH at study entry were significantly and negatively associated with survival (P<0.01). CONCLUSION: No objective responses were seen in the primary end point. However, elevated serum levels of PTH, a common feature of advanced prostate cancer, were reduced by paricalcitol. Because elevated PTH is associated with increased cardiovascular and skeletal morbidity, including an increased risk for pathologic fracture, further evaluation of paricalcitol in the reduction of skeletal morbidity in advanced prostate cancer is warranted.

Aged↗

PubMed2005

Society of Urologic Oncology position statement: redefining the management of hormone-refractory prostate carcinoma.

Because patients with hormone-refractory prostate carcinoma are a very diverse group, management of these patients represents a unique challenge. Despite much research, to the authors' knowledge few studies published to date have provided definitive treatment answers. The Society of Urologic Oncology (SUO) convened a multidisciplinary panel of urologists, oncologists, and radiation oncologists to develop a treatment algorithm for patients with hormone-refractory prostate carcinoma. The resulting treatment outline was based on a review of the literature review and on the expert opinions of the panelists. The current article provided a logical progression of treatment choices that included hormonal manipulations, chemotherapeutic options, and adjunctive therapies. Future clinical trials and therapies were also discussed by the authors. Management strategies should be targeted toward the individual patient. Although significant progress has been made in understanding and treating hormone-refractory prostate carcinoma, earlier interventions would be ideal and better therapeutic approaches to prolong survival are necessary.

Algorithms↗

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

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

A system for studying epithelial-stromal interactions reveals distinct inductive abilities of stromal cells from benign prostatic hyperplasia and prostate cancer.

The development of normal and abnormal glandular structures in the prostate is controlled at the endocrine and paracrine levels by reciprocal interactions between epithelium and stroma. To study these processes, it is useful to have an efficient method of tissue acquisition for reproducible isolation of cells from defined histologies. Here we assessed the utility of a standardized system for acquisition and growth of prostatic cells from different regions of the prostate with different pathologies, and we compared the abilities of stromal cells from normal peripheral zone, benign prostatic hyperplasia (BPH-S), and cancer to induce the growth of a human prostatic epithelial cell line (BPH-1) in vivo. Using the tissue recombination method, we showed that grafting stromal cells (from any histology) alone or BPH-1 epithelial cells alone produced no visible grafts. Recombining stromal cells from normal peripheral zone with BPH-1 cells also produced no visible grafts (n = 15). Recombining BPH-S with BPH-1 cells generated small, well-organized, and sharply demarcated grafts approximately 3-4 mm in diameter (n = 9), demonstrating a moderate inductive ability of BPH-S. Recombining stromal cells from cancer with BPH-1 cells generated highly disorganized grafts that completely surrounded the host kidney and invaded into adjacent renal tissue, demonstrating induction of an aggressive phenotype. We conclude that acquisition of tissue from toluidine blue dye-stained specimens is an efficient method to generate high-quality epithelial and/or stromal cultures. Stromal cells derived by this method from areas of BPH and cancer induce epithelial cell growth in vivo, which mimics the natural history of these diseases.

Cell Communication↗

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

Deficient nucleotide excision repair capacity enhances human prostate cancer risk.

Prostate cancer (CaP) is the most commonly diagnosed non-skin cancer and the second leading cause of cancer death in American men. The etiology of CaP is not fully understood. Because most of the DNA adducts generated by some CaP-related carcinogens, including polycyclic aromatic hydrocarbons, heterocyclic amines, and pesticides, are removed by the nucleotide excision repair (NER) pathway, we pilot tested the hypothesis that CaP is associated with deficient NER capacity (NERC), measured by a plasmid-based host reactivation assay. Using cryopreserved lymphocytes collected in an ongoing, clinic-based case-control study, our results showed that the mean NERC was significantly lower (P = 0.03) in 140 cases (mean +/- SD, 8.06 +/- 5.17) than in 96 controls (9.64 +/- 5.49). There was a significant association between below-median NERC and CaP risk: odds ratio (OR), 2.14; 95% confidence interval (CI), 1.19-3.86, after adjustment for age, race/ethnicity, smoking history, benign prostatic hyperplasia, and family history. This association was stronger in younger (<60 years of age) subjects (OR, 3.98; 95% CI, 1.13-14.02) compared with older (> or = 60) subjects (OR, 1.74; 95% CI, 0.90-3.37). When we stratified NERC values by quartiles of controls, there was a significant dose-dependent association between lower NERC and elevated CaP risk (p (test for linear trend), 0.01). Compared with the highest quartile of NERC as the referent group, the adjusted ORs for the 75th, 50th, and 25th quartiles were: 1.09 (95% CI, 0.46-2.59); 1.81 (95% CI, 0.77-4.27); and 2.63 (95% CI, 1.17-5.95), respectively. This pilot study is the first direct evidence associating deficient NERC with human CaP risk.

Aged↗

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↗

PubMed2004

Utility of frozen section analysis of resection margins during partial nephrectomy.

OBJECTIVES: To evaluate the utility of routine intraoperative frozen-section histologic analysis during partial nephrectomy to ensure negative surgical margins. Partial nephrectomy has gained acceptance for surgical treatment of small renal cancers. Many surgeons send specimens for intraoperative frozen section histologic analysis to ensure negative margins. METHODS: We reviewed the records of 78 patients who underwent partial nephrectomy for presumed malignancy. Patient demographics, intraoperative findings, and pathologic and clinical outcomes were analyzed. RESULTS: Seventy-nine partial nephrectomies were performed in 78 patients. Frozen sections were obtained intraoperatively in 76 cases. In 1 case (1.3%), a single margin was interpreted as positive for carcinoma, prompting deeper resection. The final histopathologic finding was interpreted as angiomyolipoma rather than carcinoma. The final pathologic examination revealed renal cell carcinoma in 52 (66%) of 79 cases. The mean oncologic follow-up was 16.2 months. One local recurrence was noted (1.9%). It arose in the resection bed 19 months after removal of a 4.5-cm tumor (pathologic Stage T3a). Both intraoperative frozen section margins and final pathologic margins were negative in this case. One patient developed pulmonary metastases and represented the only metastatic recurrence, as well as the only cancer-related death in our cohort (1.9%). CONCLUSIONS: Our data suggest that when partial nephrectomy is performed with attention to excising a perimeter of grossly normal-appearing parenchyma, sending specimens for intraoperative frozen section analyses may provide an unnecessary expense without providing meaningful, reliable information. Additional studies, including larger cohorts and extended follow-up, are needed to support these results.

Adenoma, Oxyphilic↗

PubMed2004

Neuroblastoma in an adult.

Neuroblastoma is extremely rare in adults. Advances in classification and therapy have been recently made by an analysis of pediatric tumors. We present the case of a 39-year-old man who had Stage 1 neuroblastoma with unfavorable histologic features that was treated with surgery only. Neuroblastoma should be considered as a diagnosis for adult patients with a suprarenal mass and, if confirmed, neuroblastoma in adults should be classified and treated according to pediatric guidelines.

Adrenal Gland Neoplasms↗

PubMed2004

Bladder cancer.

PURPOSE OF REVIEW: This article reviews recent advances in the diagnosis and management of bladder cancer. RECENT FINDINGS: Bladder cancer is a significant cause of morbidity and mortality. Recent research has attempted to improve the care of patients with this disease. Evidence suggests that bacillus Calmette-Guerin is the most effective intravesical therapy for the treatment of superficial bladder cancer and that maintenance therapy is superior to an induction course alone. In patients with muscle-invasive disease, nodal status and extent of lymphadenectomy have been shown to correlate with survival after radical cystectomy. The role of chemotherapy in the treatment of bladder cancer continues to evolve as well. Neoadjuvant chemotherapy has recently demonstrated a survival benefit, and trials are ongoing to define the optimal regimen of chemotherapy for urothelial carcinoma. SUMMARY: Improved understanding and advancements in the management of all stages of bladder cancer continue to improve the care of patients with this disease.

Humans↗

PubMed2004

Percutaneous CT-guided radiofrequency ablation of renal neoplasms: factors influencing success.

OBJECTIVE: The objective of our study was to evaluate the success rate for radiofrequency ablation of renal tumors and to determine the risk of serious complications. CONCLUSION: No serious complications occurred after 27 CT-guided radiofrequency ablation sessions in 22 patients. In total, no residual tumor was detected on follow-up contrast-enhanced CT or MRI 1-35 months (mean, 7 months) after final tumor ablation in 20 (91%) of 22 patients. Two patients with residual viable tumor deferred further treatment. Complete tumor ablation was achieved after a single treatment session in 83% of patients, and in 8% of patients after subsequent ablation sessions. Size was the major determinant for achieving tumor eradication with a single session of ablation, with all 11 tumors 3 cm or smaller being completely ablated after one session. Tumor location, histology, and the presence of renal disease did not correlate with treatment success. Contrast-enhanced CT performed immediately after ablation is reliable to exclude residual viable tumor. CT-guided radiofrequency ablation of renal tumors is safe and has a high rate of success in the treatment of small renal tumors, with no evidence of recurrence at midterm follow-up of treated patients.

Aged↗