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Biomedical subjects

William R Berry

Publications and source records attributed to William R Berry.

9 recordsLinked to original sources
PubMed2006

Hormone refractory prostate cancer: Management and advances.

Effective therapeutic options have not existed for prostate cancer progressing after androgen deprivation therapy until very recently. Secondary hormonal manipulations offer marginal benefits. Docetaxel based chemotherapy has been demonstrated to extend survival and change the natural history of the disease in two large randomized trials. These studies have provided the impetus to combine docetaxel with novel biologic agents to further consolidate the gains in long-term outcome. With the arrival of exciting agents including vaccines, monoclonal antibodies, bone-targeted drugs, antisense oligonucleotides, anti-angiogenic drugs and small molecule receptor tyrosine kinase inhibitors, the future treatment of prostate cancer appears promising.

Androgen Antagonists↗
PubMed2006

Systemic chemotherapy for urothelial cancer.

Although metastatic transitional cell carcinoma of the bladder and urothelium commonly responds to first-line chemotherapy, eventual progression is nearly universal. Current salvage therapy for progressive disease after first-line chemotherapy is ineffective, and such patients are candidates for clinical trials. Neoadjuvant chemotherapy improves long-term outcome and provides an exciting paradigm for the rapid development of systemic therapy. Neoadjuvant chemotherapy with or without radiation also facilitates bladder conservation in patients who attain pathologic complete remission. Definitive data supporting adjuvant chemotherapy are lacking. With the unraveling of bladder cancer biology and the discovery of novel agents targeting several carcinogenic pathways, the future of therapy for transitional cell carcinoma appears promising.

Antineoplastic Agents↗
PubMed2005

The evolving role of chemotherapy in androgen-independent (hormone-refractory) prostate cancer.

Over the last decade, much progress has been made in the treatment of advanced hormone-refractory prostate cancer (HRPC). The mitoxantrone-prednisone drug combination was approved in the United States based on palliative end points and became the standard of care despite the lack of survival benefit. Docetaxel demonstrated clinical activity in HRPC on weekly and every-3-weeks schedules as evidenced by decreases in prostate-specific antigen (PSA) values that were higher than those traditionally seen with other chemotherapy regimens. The TAX 327 phase 3 trial was designed to further define the role of docetaxel in HRPC. A total of 1006 patients were randomized to receive docetaxel 75 mg/m2 every 3 weeks, docetaxel 30 mg/m2 weekly for 5 of 6 weeks, or mitoxantrone 12 mg/m2 every 3 weeks. All patients received daily prednisone. The primary study objective was survival, with secondary objectives of pain response, PSA decrease, measurable response, and quality of life (QOL). Compared with mitoxantrone, a survival benefit was demonstrated for docetaxel every 3 weeks (P = 0.009) and for the combined docetaxel arms (P = 0.03, respectively). Decreases in PSA values were superior with docetaxel (45% for the every-3-weeks regimen, P = 0.0005; 47% for the weekly regimen, P < 0.0001). Pain improvement was superior in the every-3-weeks docetaxel arm (P = 0.0107), and QOL was significantly better with both docetaxel regimens (every 3 weeks, P = 0.009; weekly, P = 0.005). Serious toxicity was rare in all arms. Given these compelling results, it can be concluded that docetaxel represents a new standard of care for the treatment of HRPC.

Antineoplastic Agents↗
PubMed2004

Docetaxel plus prednisone or mitoxantrone plus prednisone for advanced prostate cancer.

BACKGROUND: Mitoxantrone plus prednisone reduces pain and improves the quality of life in men with advanced, hormone-refractory prostate cancer, but it does not improve survival. We compared such treatment with docetaxel plus prednisone in men with this disease. METHODS: From March 2000 through June 2002, 1006 men with metastatic hormone-refractory prostate cancer received 5 mg of prednisone twice daily and were randomly assigned to receive 12 mg of mitoxantrone per square meter of body-surface area every three weeks, 75 mg of docetaxel per square meter every three weeks, or 30 mg of docetaxel per square meter weekly for five of every six weeks. The primary end point was overall survival. Secondary end points were pain, prostate-specific antigen (PSA) levels, and the quality of life. All statistical comparisons were against mitoxantrone. RESULTS: As compared with the men in the mitoxantrone group, men in the group given docetaxel every three weeks had a hazard ratio for death of 0.76 (95 percent confidence interval, 0.62 to 0.94; P=0.009 by the stratified log-rank test) and those given weekly docetaxel had a hazard ratio for death of 0.91 (95 percent confidence interval, 0.75 to 1.11; P=0.36). The median survival was 16.5 months in the mitoxantrone group, 18.9 months in the group given docetaxel every 3 weeks, and 17.4 months in the group given weekly docetaxel. Among these three groups, 32 percent, 45 percent, and 48 percent of men, respectively, had at least a 50 percent decrease in the serum PSA level (P<0.001 for both comparisons with mitoxantrone); 22 percent, 35 percent (P=0.01), and 31 percent (P=0.08) had predefined reductions in pain; and 13 percent, 22 percent (P=0.009), and 23 percent (P=0.005) had improvements in the quality of life. Adverse events were also more common in the groups that received docetaxel. CONCLUSIONS: When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plus prednisone.

Adenocarcinoma↗
PubMed2004

Phase II randomized trial of weekly paclitaxel with or without estramustine phosphate in progressive, metastatic, hormone-refractory prostate cancer.

This study was conducted to determine the similarity of response rates and safety produced by weekly paclitaxel with or without oral estramustine in patients with metastatic hormone-refractory prostate cancer. Between December 1998 and December 1999, 163 patients were randomized to receive 28-day cycles of paclitaxel 100 mg/m2 on days 2, 9, and 16 plus estramustine 280 mg orally 3 times a day on days 1-3, 8-10, and 15-17, or to receive paclitaxel 100 mg/m2 alone on days 1, 8, and 15. Objective response was defined as a > oe = 50% decrease in prostate-specific antigen (PSA) maintained for 4 weeks with stable or improved performance status. Response rates included 37 partial responses for paclitaxel/estramustine (47%) and 22 partial responses for paclitaxel (27%; P < 0.01). Median duration of response was 15.1 months for paclitaxel/estramustine and 15.5 months for paclitaxel; median survival was 16.1 months and 13.1 months, respectively (P = 0.049). Common toxicities for both treatments included neutropenia, gastrointestinal events, neuropathy, and asthenia. Thromboembolic events were more frequent in the paclitaxel/estramustine arm (no prophylactic anticoagulants). The rate of PSA decline for paclitaxel/estramustine was almost 2 times that of paclitaxel (47% vs. 27%), with acceptable toxicity. Multivariate analysis of prognostic factors affecting survival was not significant for treatment arm (P = 0.08). Although the incidence of thromboembolic events appeared to be increased in the paclitaxel/ estramustine arm, the addition of estramustine was responsible for a 20% increase in the rate of PSA decline. Neither treatment arm had significant impact on quality of life as measured by the Functional Assessment of Cancer Therapy-Prostate quality of life questionnaire. This study produced encouraging data; further studies of paclitaxel/ estramustine are recommended.

Aged↗
PubMed2003

Fourteen-day CHOP supported with granulocyte colony-stimulating factor in patients with aggressive non-Hodgkin's lymphoma: results of a phase II study.

The safety and efficacy of compressed-cycle (14-day) standard-dose CHOP (cyclophosphamide/doxorubicin/vincristine/prednisone) supported with prophylactic recombinant granulocyte colony-stimulating factor (G-CSF; filgrastim) were evaluated in patients with aggressive non-Hodgkin's lymphoma (NHL). Patients with intermediate- or high-grade NHL (Working Formulation groups D-H and J; N = 120), accrued from 25 clinical practices, were given 6 cycles of standard-dose CHOP every 14 days. Granulocyte colony-stimulating factor 5 microg/kg was given daily subcutaneously in each cycle, starting on day 2 and continuing until the absolute neutrophil count was = 10000/microL. The overall response rate was 89%, with complete responses (CRs) in 52 of 120 patients (43%) and partial responses in 55 (46%). These results are consistent with previously reported outcomes from trials in this population. Of the 720 chemotherapy cycles planned for all patients, 615 (85%) were given on time at full dose. The median relative dose intensity (RDI) of cyclophosphamide and doxorubicin was 99%; the RDI of vincristine was 73%. In the 53 patients = 60 years of age, 80% of the chemotherapy cycles were given on time at full dose, with median RDIs similar to those in the entire population. Response rates in the older patients were also similar, with CRs in 24 patients (45%) and partial responses in 21 (40%). Hematologic toxicity was significant but tolerable, with no treatment-related deaths. At a median follow-up of 20.6 months, 77% of patients were still alive. Standard-dose CHOP administered every 14 days with prophylactic G-CSF support was delivered as planned in most patients and produced response rates comparable with those with CHOP given every 3 weeks, without exceptional toxicity.

Adolescent↗