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Siu-Long Yao

Publications and source records attributed to Siu-Long Yao.

8 recordsLinked to original sources
PubMed2007

Population based study of hormonal therapy and survival in men with metastatic prostate cancer.

PURPOSE: Although the palliative benefits of hormonal therapy for metastatic prostate cancer are widely recognized, little information is available regarding the effect of hormonal therapy on cancer specific and overall survival, and the types of patients who might benefit the most or least from hormonal therapy. MATERIALS AND METHODS: Prostate cancer specific and overall survival according to hormonal therapy use was determined by the Kaplan-Meier method in 6,098 men 65 years or older diagnosed with metastatic prostate cancer in 1991 to 1999 who were identified through the population based Surveillance, Epidemiology, and End Results, and Medicare linked database. Cox proportional hazards and propensity score methods were used to adjust for potential confounders, such as disease status and patient comorbidity. RESULTS: Propensity score adjusted median overall survival was 26 months in men who received hormonal therapy compared with 13 months in those who did not (HR 0.66, 95% CI 0.17-0.70, p <0.0001). The benefit of hormonal therapy was observed across all comorbidity strata and races. Effects were most evident in patients with poorly differentiated cancer (cancer specific mortality in favor of treatment HR 0.60, 95% CI 0.53-0.69, p <0.001). Benefit was not found in patients with well differentiated cancer (cancer specific mortality in favor of no treatment HR 1.92, 95% CI 0.90-4.10, p = 0.09). CONCLUSIONS: Hormonal therapy is associated with improved prostate cancer specific and overall survival in men with poorly differentiated cancer. Improved survival does not appear evident in men with well differentiated disease.

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PubMed2006

Use of hormonal therapy in men with metastatic prostate cancer.

PURPOSE: Bilateral orchiectomy or luteinizing hormone releasing hormone agonists represent the standard of care for metastatic prostate cancer. In this population based study we assessed the use rates of these therapies in men who died of prostate cancer. MATERIAL AND METHODS: A total of 9,110 men 65 years or older who died of prostate cancer in 1991 to 2000 were identified through the population based Surveillance, Epidemiology and End Results, and Medicare linked database to determine hormonal therapy use rates. A modified Poisson regression model was used to estimate the adjusted effects of various factors associated with hormone use. RESULTS: Approximately 38% of black and 25% of white men did not receive hormonal therapy before dying of prostate cancer. After adjusting for cancer status at diagnosis and other potential confounding factors black race and residence in low income areas were associated with lower hormonal therapy use (relative risk 0.73, 95% CI 0.67 to 0.80 and 0.91, 95% CI 0.85 to 0.98, respectively). Hormonal therapy use was most comprehensive in the Northeast. CONCLUSIONS: A substantial number of men who die as a consequence of prostate cancer never receive hormonal therapy. The use of hormonal therapy varies significantly. Further studies are warranted to determine factors that may be associated with the incomplete use of hormonal therapy for metastatic prostate cancer.

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PubMed2004

Changing patterns in competing causes of death in men with prostate cancer: a population based study.

PURPOSE: We examined trends in hospitalization and death in men with prostate cancer to determine whether outcomes have changed with time in men diagnosed and treated for this disorder. MATERIALS AND METHODS: A population based cohort study of 180973 patients with prostate cancer in the 1979 to 1996 Surveillance, Epidemiology and End Results cancer registry and 450448 admissions in the 1987 to 1996 Surveillance, Epidemiology and End Results-Medicare linked database were analyzed. ORs derived from logistic regression were used to assess time trends in mortality and hospitalization. Multinominal logistic regression was used to obtain the adjusted proportions of deaths due to various causes in different years. RESULTS: In men with prostate cancer the risk of death from cancer was 39.7% (OR = 0.61, 95% CI = 0.56 to 0.66), which was lower in 1995 to 1996 than in 1979 to 1980. Decreases in prostate cancer death were greater than those in cardiovascular disorders (OR = 0.85, 95% CI = 0.78 to 0.92) and evident even in men with nonlocalized disease. Overall nonprostate cancer causes of mortality increased (OR = 1.65, 95% CI = 1.52 to 1.79) and ultimately exceeded that due to prostate cancer. By 1995 to 1996 the proportion of prostate cancer deaths was similar to that of cardiovascular disorders (27.7% and 26.6%, respectively) and substantially less than that of all other sources combined (45.7%). Similar effects were observed for prostate cancer (OR = 0.40, 95% CI = 0.37 to 0.42) and nonprostate cancer (OR = 2.51, 95% CI = 2.36 to 2.68) hospitalizations. CONCLUSIONS: In men with prostate cancer decreases in prostate cancer hospitalization and mortality have been greater than those in competing diseases with time. Most deaths in patients with prostate cancer, including those with nonlocalized disease, are now due to nonprostate cancer causes.

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PubMed2003

Prostate-specific antigen screening in elderly men.

Although the efficacy of prostate-specific antigen (PSA) screening for prostate cancer has not been established, it is widely used. However, despite the overall controversy regarding PSA screening, there has been general agreement that elderly men (i.e., those aged 75 years or older) should not be screened. By using a nationally representative sample of 7889 men who participated in the 2000 National Health Interview Survey, we found that the rate of PSA screening among men aged 75 or older was 32.5% (95% confidence interval [CI] = 28.8% to 36.1%), which was greater than that of fecal occult blood screening among men of the same age (22.8%, 95% CI = 19.2% to 26.4%) and was comparable with that of annual Pap smear screening among women aged 75 years or older (29.0%, 95% CI = 26.6% to 31.3%). Among screened elderly men, 88.4% (95% CI = 82.3% to 92.6%) reported that their doctor first suggested screening and 66.5% (95% CI = 59.7% to 73.3%) reported that the risks and benefits of screening were discussed before screening. We conclude that strategies are needed to increase understanding of the risks and benefits of PSA screening among elderly men.

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PubMed2003

An evidence-based approach to prostate cancer follow-up.

The follow-up required for patients with prostate cancer is critically dependent upon the stage of disease and the ultimate goal for treatment. A major difficulty in follow-up in prostate cancer is the lack of data on outcome of various treatment modalities. Additionally, there is a lack of data on the use of treatment modalities early in the course of prostate cancer. Despite these limitations, there is a need to develop an approach to follow these patients pending further study. In this review, we critically assess the natural course of untreated prostate cancer, the complications of local therapy, and the controversy over early versus delayed hormonal therapy. As a result of this discussion, common themes emerge. Most patients diagnosed with prostate cancer die of causes other than prostate cancer such as cardiovascular disease and therefore require additional follow-up. Since patients experience local problems such as urinary obstruction more commonly than symptomatic metastatic disease, instruments to assess urinary symptoms are discussed. Finally, follow-up as a means to determine eligibility for clinical studies is discussed.

Continuity of Patient Care↗
PubMed2002

Characterization of a novel prostate-specific antigen-activated peptide-doxorubicin conjugate in patients with prostate cancer.

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.

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PubMed2002

Preclinical and clinical pharmacodynamic assessment of L-778,123, a dual inhibitor of farnesyl:protein transferase and geranylgeranyl:protein transferase type-I.

Farnesyl:protein transferase (FPTase) inhibitors were developed as anti-Ras drugs, but they fail to inhibit Ki-Ras activity because Ki-Ras can be modified by geranylgeranyl:protein transferase type-I (GGPTase-I). L-778,123, an inhibitor of FPTase and GGPTase-I, was developed in part because it can completely inhibit Ki-Ras prenylation. To support the clinical development of L-778,123, we developed pharmacodynamic assays using peripheral blood mononuclear cells (PBMCs) to measure the inhibition of prenylation of HDJ2 and Rap1A, proteins that are FPTase- and GGPTase-I substrates, respectively. We validated these assays in animal models and show that inhibition of HDJ2 prenylation in mouse PBMCs correlates with the concentration of FPTase inhibitors in blood. In dogs, continuous infusion of L-778,123 inhibited both HDJ2 and Rap1A prenylation in PBMCs, but we did not detect inhibition of Ki-Ras prenylation. We reported previously results from the first L-778,123 Phase I trial that showed a dose-dependent inhibition of HDJ2 farnesylation in PBMCs. In this report, we present additional analysis of patient samples from this trial and a second Phase I trial of L-778,123, and demonstrate the inhibition of both HDJ2 and Rap1A prenylation in PBMC samples. This study represents the first demonstration of GGPTase-I inhibition in humans. However, no inhibition of Ki-Ras prenylation by L-778,123 was detected in patient samples. These results confirm the pharmacologic profile of L-778,123 in humans as a dual inhibitor of FPTase and GGPTase-I, but indicate that the intended target of the drug, Ki-Ras, was not inhibited.

Alkyl and Aryl Transferases↗