Publications by authors named "Amy M Lin"

28 Publications

  • Page 1 of 1

Factors Associated With Participation in the Chronic Disease Self-Management Program: Findings From the SUCCEED Trial.

Stroke 2020 10 11;51(10):2910-2917. Epub 2020 Sep 11.

Department of Neurology, University of Southern California (A.M.L., M.A.-R., T.S.-T., N.S., A.T.), Los Angeles.

Background And Purpose: Self-management programs may improve quality of life and self-efficacy for stroke survivors, but participation is low. In a randomized controlled trial of a complex, multidisciplinary, team-based secondary stroke prevention intervention, we offered participants Chronic Disease Self-Management Program (CDSMP) workshops in addition to clinic visits and home visits. To enhance participation, workshops were facilitated by community health workers who were culturally and linguistically concordant with most participants and scheduled CDSMP sessions at convenient venues and times. Over time, we implemented additional strategies such as free transportation and financial incentives. In this study, we aimed to determine factors associated with CDSMP participation and attendance.

Methods: From 2014 to 2018, 18 CDSMP workshop series were offered to 241 English and Spanish-speaking individuals (age ≥40 years) with recent stroke or transient ischemic attack. Zero-inflated Poisson regression was used to identify factors associated with participation and attendance (ie, number of sessions attended) in CDSMP. Missing values were imputed using multiple imputation methods.

Results: Nearly one-third (29%) of intervention subjects participated in CDSMP. Moderate disability and more clinic/home visits were associated with participation. Participants with higher numbers of clinic and home visits (incidence rate ratio [IRR], 1.06 [95% CI, 1.01-1.12]), severe (IRR, 2.34 [95% CI, 1.65-3.31]), and moderately severe disability (IRR, 1.55 [95% CI, 1.07-2.23]), and who enrolled later in the study (IRR, 1.12 [95% CI, 1.08-1.16]) attended more sessions. Individuals with higher chaos scores attended fewer sessions (IRR, 0.97 [95% CI, 0.95-0.99]).

Conclusions: Less than one-third of subjects enrolled in the SUCCEED (Secondary Stroke Prevention by Uniting Community and Chronic Care Model Teams Early to End Disparities) intervention participated in CDSMP; however, participation improved as transportation and financial barriers were addressed. Strategies to address social determinants of health contributing to chaos and engage individuals in healthcare may facilitate attendance. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01763203.
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http://dx.doi.org/10.1161/STROKEAHA.119.028022DOI Listing
October 2020

Less Than Ideal.

Stroke 2018 Dec 7:STROKEAHA118022644. Epub 2018 Dec 7.

From the Department of Neurology, University of Southern California, Los Angeles (A.M.L., N.S., A.T.).

Background and Purpose- The American Heart Association's Life's Simple 7 (LS7) defines ideal cardiovascular health by 7 metrics: not smoking, regular physical activity, normal body mass index, blood pressure, plasma glucose, and total cholesterol levels, and a healthy diet. We assessed prevalence and predictors of ideal LS7 among US stroke survivors. Methods- Among 67 514 participants in the National Health and Nutrition Examination Surveys from 1988 to 1994 and 1999 to 2014, 1597 adults (≥18 years) had self-reported history of stroke. LS7 metrics were categorized as poor, intermediate, and ideal; ideal LS7 scores were calculated (1 point for each ideal metric met). Trends in poor, intermediate, and ideal cardiovascular health were assessed. Odds of low (0-1) versus high (≥4) ideal LS7 scores were assessed according to sex, race, poverty income ratio, and education level, before and after adjusting for covariates. Results- Only 1 participant met all ideal LS7 metrics. The proportion with low LS7 score increased from 17.9% in 1988 to 1994 to 35.4% in 2011 to 2014 ( P<0.001). Over that time frame, prevalence of poor blood pressure (≥140/90 mm Hg) and poor cholesterol (≥240 mg/dL) decreased (45.2%-26.5% and 37.2%-10.3%), whereas prevalence of poor body mass index (≥30 kg/m), poor diet (healthy eating index score <50), and poor physical activity (0 minutes moderate/vigorous activity per week) increased (26.9%-39.0%; 14.2%-50.6%; 44.6%-70.9%; all P<0.05). After adjustment, black race (odds ratio, 2.29; 95% CI, 1.17-4.48), poverty income ratio ≤200% (odds ratio, 2.20, 95% CI, 1.11-4.36), and ≤12th grade education (odds ratio, 4.50; 95% CI, 2.27-8.92) were associated with low ideal LS7 scores. Conclusions- Over the past 3 decades, blood pressure and cholesterol control among stroke survivors improved, but rates of obesity, poor diet, and physical inactivity increased. Stroke survivors who are black, poor, or less educated are less likely to have ideal cardiovascular health.
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http://dx.doi.org/10.1161/STROKEAHA.118.022644DOI Listing
December 2018

Itraconazole as a Noncastrating Treatment for Biochemically Recurrent Prostate Cancer: A Phase 2 Study.

Clin Genitourin Cancer 2019 Feb 24;17(1):e92-e96. Epub 2018 Sep 24.

University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA. Electronic address:

Background: Patients with biochemically recurrent prostate cancer and short prostate-specific antigen doubling time (PSADT) are at risk for metastasis yet may wish to avoid androgen deprivation therapy. Itraconazole may have antitumor activity without affecting circulating androgen levels. We therefore evaluated itraconazole as a potentially noncastrating treatment approach in biochemically recurrent prostate cancer.

Patients And Methods: Patients with biochemically recurrent prostate cancer and PSADT ≤ 15 months, with serum testosterone > 150 ng/dL, were prospectively enrolled. The primary end point was the proportion of patients who experienced ≥ 50% decline from baseline in serum prostate-specific antigen (PSA) by week 12.

Results: Twenty-one patients were enrolled. The median (range) age, baseline PSA, and PSADT at study entry was 72 (49-76) years, 7.6 (1.5-45.5) ng/mL, and 5.7 (1.2-13.0) months, respectively. Among 19 patients with evaluable data, 1 patient (5%) had a > 50% PSA decline. Nine patients (47%) experienced any PSA decline (mean decline 25.0%, range 2%-60%) by week 12. Among 10 patients without a PSA decline, the on-treatment versus pretreatment PSADT was not significantly longer (median 6.8 vs. 4.3 months, P = .17). There was no significant change from baseline to week 12 in serum testosterone (median change = 32.4%, P = .21) or androstenedione (median change = -8.3%, P = .85). The most common adverse events were edema (52%), fatigue (38%), hypertension (24%), and hypokalemia (24%).

Conclusion: Itraconazole modulates serum PSA levels without lowering serum testosterone. However, the magnitude of effect is modest, and treatment carries risk of toxicities associated with mineralocorticoid excess.
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http://dx.doi.org/10.1016/j.clgc.2018.09.013DOI Listing
February 2019

A Phase II Trial of Selinexor, an Oral Selective Inhibitor of Nuclear Export Compound, in Abiraterone- and/or Enzalutamide-Refractory Metastatic Castration-Resistant Prostate Cancer.

Oncologist 2018 06 27;23(6):656-e64. Epub 2018 Feb 27.

Division of Hematology/Oncology, University of California, San Francisco, San Francisco, California, USA.

Lessons Learned: In abiraterone- and/or enzalutamide-refractory metastatic castration-resistant prostate cancer (mCRPC) patients, selinexor led to prostate-specific antigen and/or radiographic responses in a subset of patients, indicating clinical activity in this indication.Despite twice-a-week dosing and maximal symptomatic management, selinexor was associated with significant anorexia, nausea, and fatigue in mCRPC patients refractory to second-generation anti-androgen therapies, limiting further clinical development in this patient population.This study highlights the challenge of primary endpoint selection for phase II studies in the post-abiraterone and/or post-enzalutamide mCRPC space.

Background: Selinexor is a first-in-class selective inhibitor of nuclear export compound that specifically inhibits the nuclear export protein Exportin-1 (XPO-1), leading to nuclear accumulation of tumor suppressor proteins.

Methods: This phase II study evaluated the efficacy and tolerability of selinexor in patients with metastatic castration-resistant prostate cancer (mCRPC) refractory to abiraterone and/or enzalutamide.

Results: Fourteen patients were enrolled. Selinexor was initially administered at 65 mg/m twice a week (days 1 and 3) and was subsequently reduced to 60 mg flat dose twice a week (days 1 and 3), 3 weeks on, 1 week off, to improve tolerability. The median treatment duration was 13 weeks. At a median follow-up of 4 months, two patients (14%) had ≥50% prostate-specific antigen (PSA) decline, and seven patients (50%) had any PSA decline. Of eight patients with measurable disease at baseline, two (25%) had a partial response and four (50%) had stable disease as their best radiographic response. Five patients (36%) experienced serious adverse events (SAEs; all unrelated to selinexor), and five patients (36%) experienced treatment-related grade 3-4 AEs. The most common drug-related adverse events (AEs) of any severity were anorexia, nausea, weight loss, fatigue, and thrombocytopenia. Three patients (21%) came off study for unacceptable tolerability.

Conclusion: Selinexor demonstrated clinical activity and poor tolerability in mCRPC patients refractory to second-line anti-androgenic agents.
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http://dx.doi.org/10.1634/theoncologist.2017-0624DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6067936PMC
June 2018

High-Dose Abiraterone Acetate in Men With Castration Resistant Prostate Cancer.

Clin Genitourin Cancer 2017 12 3;15(6):733-741.e1. Epub 2017 Jun 3.

Division of Genitourinary Medical Oncology, University of California, San Francisco, CA.

Background: Abiraterone acetate (AA) inhibits androgen biosynthesis and prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC) when combined with prednisone (P). Resistance to therapy remains incompletely understood. In this open-label, single-arm, multicenter phase II study we investigated the clinical benefit of increasing the dose of AA at the time of resistance to standard-dose therapy.

Patients And Methods: Eligible patients had progressive mCRPC and started AA 1000 mg daily and P 5 mg twice daily. Patients who achieved any prostate-specific antigen (PSA) decline after 12 weeks of therapy continued AA with P until PSA or radiographic progression. At progression, AA was increased to 1000 mg twice daily with unchanged P dosing. Patients were monitored for response to therapy for a minimum of 12 weeks or until PSA or radiographic progression. The primary end point was PSA decline of at least 30% after 12 weeks of therapy at the increased dose of AA.

Results: Forty-one patients were enrolled from March 2013 through March 2014. Thirteen men experienced disease progression during standard-dose therapy and were subsequently treated with AA 1000 mg twice per day. Therapy was well tolerated. No PSA declines ≥ 30% nor radiographic responses were observed after 12 weeks of dose-escalated therapy. Higher baseline dehydroepiandrosterone levels, lower circulating tumor cell burden, and higher pharmacokinetic levels of abiraterone and abiraterone metabolites were associated with response to standard-dose therapy.

Conclusion: Increasing the dose of abiraterone at the time of resistance has limited clinical utility and cannot be recommended. Lower baseline circulating androgen levels and interpatient pharmacokinetic variance appear to be associated with primary resistance to AA with P.
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http://dx.doi.org/10.1016/j.clgc.2017.05.026DOI Listing
December 2017

A Phase I Study of Abiraterone Acetate Combined with BEZ235, a Dual PI3K/mTOR Inhibitor, in Metastatic Castration Resistant Prostate Cancer.

Oncologist 2017 05 17;22(5):503-e43. Epub 2017 Mar 17.

University of California, San Francisco, Helen Diller Family Comprehensive Cancer Center, California, USA.

Lessons Learned: The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored.

Background: Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer. Preclinical data have shown that the two pathways compensate for each other when one is inhibited, and combined inhibition of AR and PI3K signaling may be a viable strategy to prevent or overcome castration resistance.

Methods: This phase I study evaluated the safety and tolerability of abiraterone acetate and prednisone combined with BEZ235, a dual PI3K and mTORC1/2 inhibitor, in men with progressive metastatic castration resistant prostate cancer (mCRPC) who have not received prior chemotherapy.

Results: Six patients ( = 6) were treated at the starting dose level of abiraterone acetate 1,000 mg with prednisone 5 mg twice daily and BEZ235 200 mg twice daily in a 3 + 3 dose escalation design. The study was terminated early because three of the six patients (50%) experienced dose-limiting toxicities: grade 3 mucositis, grade 3 hypotension, and grade 4 dyspnea and pneumonitis. All six patients had previously progressed on abiraterone/prednisone. The median treatment duration was 27 days (range: 3-130 days). No prostate-specific antigen (PSA) decline or objective response were observed.

Conclusion: The combination of standard-dose abiraterone/prednisone with BEZ235 200 mg twice daily was poorly tolerated in patients with mCRPC. The on-target and off-target effects of dual PI3K and mTORC inhibition likely contributed to the unacceptable toxicity profile. 2017;22:503-e43.
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http://dx.doi.org/10.1634/theoncologist.2016-0432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5423513PMC
May 2017

A multicenter phase I study of cabazitaxel, mitoxantrone, and prednisone for chemotherapy-naïve patients with metastatic castration-resistant prostate cancer: A department of defense prostate cancer clinical trials consortium study.

Urol Oncol 2017 04 1;35(4):149.e7-149.e13. Epub 2017 Feb 1.

Department of Medicine, Division of Hematology/Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA.

Background: Cabazitaxel plus prednisone has significant activity in patients with chemotherapy-naïve and pretreated metastatic castration-resistant prostate cancer (mCRPC). Mitoxantrone has antitumor activity in mCRPC and nonoverlapping mechanism of action and toxicity profile.

Objective: To establish the maximally tolerated dose of the combination of cabazitaxel, mitoxantrone, and prednisone.

Methods And Materials: Patients with chemotherapy-naïve mCRPC were prospectively enrolled in a multicenter phase 1 trial. Cabazitaxel 20 and 25mg/m were each evaluated in combination with escalating doses of mitoxantrone (starting dose 4mg/m), given with prednisone 5mg twice daily.

Results: A total of 25 patients were enrolled, with median age of 67 (range: 51-78) and prostate-specific antigen of 66.8ng/ml (range: 3-791.2). There were 4 dose-limiting toxicities (febrile neutropenia, n = 3; sepsis, n = 1). The maximally tolerated dose was cabazitaxel 20mg/m plus mitoxantrone 12mg/m. The most common treatment-related grade≥3 related adverse events included neutropenia (n = 8; 32%), febrile neutropenia (n = 5; 20%), and thrombocytopenia (n = 4; 16%). The median number of treatment cycles was 8 (range: 2 to 19+). Decline in prostate-specific antigen to≥50% from baseline was observed in 15 patients (60%). Objective responses were observed in 10/14 (71%) evaluable patients. The median radiographic progression-free survival was 14.5 months (95% CI: 8.0-not reached (NR)), and median overall survival was 23.3 months (95% CI: 14.3-NR).

Conclusions: The approved single-agent doses of mitoxantrone and cabazitaxel were safely combined. The combination led to durable tumor responses in most patients. Further study of the combination is warranted.
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http://dx.doi.org/10.1016/j.urolonc.2016.11.005DOI Listing
April 2017

Systemic GM-CSF Recruits Effector T Cells into the Tumor Microenvironment in Localized Prostate Cancer.

Cancer Immunol Res 2016 11 29;4(11):948-958. Epub 2016 Sep 29.

University of California, San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California.

Granulocytic-macrophage colony-stimulating factor (GM-CSF) is used as an adjuvant in cancer vaccine trials and has the potential to enhance antitumor efficacy with immunotherapy; however, its immunologic effects are not fully understood. Here, we report results from a phase I study of neoadjuvant GM-CSF in patients with localized prostate cancer undergoing radical prostatectomy. Patients received subcutaneous injections of GM-CSF (250 μg/m/day) daily for 2 weeks (cohort 1; n = 6), 3 weeks (cohort 2; n = 6), or 4 weeks (cohort 3; n = 6). Treatment was well tolerated with all grade 1 or 2 adverse events. Two patients had a decline in prostate-specific antigen (PSA) of more than 50%. GM-CSF treatment increased the numbers of circulating mature myeloid dendritic cells, proliferating conventional CD4 T cells, proliferating CD8 T cells, and to a lesser magnitude FoxP3 regulatory CD4 T cells. Although GM-CSF treatment did not augment antigen-presenting cell localization to the prostate, treatment was associated with recruitment of CD8 T cells to the tumor. These results suggest that systemic GM-CSF can modulate T-cell infiltration in the tumor microenvironment. Cancer Immunol Res; 4(11); 948-58. ©2016 AACR.
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http://dx.doi.org/10.1158/2326-6066.CIR-16-0042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5115633PMC
November 2016

Preexisting Levels of CD4 T Cells Expressing PD-1 Are Related to Overall Survival in Prostate Cancer Patients Treated with Ipilimumab.

Cancer Immunol Res 2015 Sep 12;3(9):1008-16. Epub 2015 May 12.

Division of Hematology/Oncology, University of California, San Francisco, California. UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.

Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) blockade can induce tumor regression and improved survival in cancer patients. This treatment can enhance adaptive immune responses without an exogenous vaccine, but the immunologic biomarkers associated with improved clinical outcome in cancer patients are not fully established. A phase Ib trial in patients with metastatic, castration-resistant prostate cancer was performed combining ipilimumab with sargramostim (GM-CSF). In addition to evaluating ipilimumab dose, patients were followed clinically for response and overall survival, and for immunomodulation of circulating T cells. PSA declines of ≥50% and radiographic responses were observed at doses of ≥3 mg/kg/dose. Timing of clinical responses could be either immediate or delayed. Durable responses were also observed off treatment. A subset of patients experienced long-term survival with or without objective clinical responses. The relationship between T-cell phenotype in peripheral blood and overall survival was examined retrospectively. We found that the treatment induced an increase in the levels of CD4(+) effector T (Teff) cells, regulatory T cells, PD-1(+) CD4 Teff cells, and PD-1(+) CD8 T cells. However, these increased levels were not associated with overall survival. Instead, low pretreatment baseline levels of PD-1(+) CD4 Teff cells were found to correlate with longer overall survival. Furthermore, baseline levels of PD-1(+) CD4 Teff cells from patients with shorter overall survival were higher than from cancer-free male control subjects. These results suggest that preexisting expression of immunologic checkpoint marker PD-1 on CD4 Teff cells may help identify patients that may benefit from ipilimumab treatment.
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http://dx.doi.org/10.1158/2326-6066.CIR-14-0227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4561203PMC
September 2015

Intermittent Chemotherapy as a Platform for Testing Novel Agents in Patients With Metastatic Castration-Resistant Prostate Cancer: A Department of Defense Prostate Cancer Clinical Trials Consortium Randomized Phase II Trial of Intermittent Docetaxel With Prednisone With or Without Maintenance GM-CSF.

Clin Genitourin Cancer 2015 Jun 9;13(3):e191-8. Epub 2014 Dec 9.

Department of Medicine, University of California San Francisco, San Francisco, CA.

Background: Immunotherapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), an agent that previously demonstrated antitumor activity, was evaluated within an intermittent chemotherapy framework of docetaxel with prednisone (D+P) in metastatic castration-resistant prostate cancer (mCRPC).

Patients And Methods: mCRPC patients with ≥ 50% prostate-specific antigen (PSA) decline after 6 cycles of D+P were randomized to either GM-CSF or observation (Obs). At disease progression (PD), D+P was reinitiated for 6 cycles followed by the same "off chemotherapy" regimen in patients eligible for chemotherapy interruption. The sequence was repeated until PD during chemotherapy, lack of PSA response to chemotherapy, or unacceptable toxicity. The primary end point was time to chemotherapy resistance (TTCR).

Results: Of 125 patients enrolled, 52 (42%) experienced ≥ 50% PSA decline on induction D+P and were randomized to GM-CSF (n = 27) or Obs (n = 25). The median time to PD was 3.3 months (95% confidence interval [CI], 2.4-3.5) and 1.5 months (95% CI, 1.5-2.4) during the initial course of GM-CSF and Obs, respectively. Twelve of 26 (46%) patients responded to a second course of D+P. Eleven randomized patients (21%) experienced PD during chemotherapy, precluding accurate assessment of TTCR. The remaining 41 randomized patients discontinued study for lack of PSA response to chemotherapy (n = 8), patient choice to not restart chemotherapy with PSA PD (n = 13), toxicity (n = 7), or study withdrawal (n = 13).

Conclusion: Conducting a prospective study in mCRPC with maintenance immunotherapy within the framework of intermittent chemotherapy was feasible. The use of PSA instead of radiographic end points limited the number of evaluable patients. This study provides important insight into designing contemporary intermittent chemotherapy trials with maintenance immunotherapy in patients with advanced prostate cancer.
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http://dx.doi.org/10.1016/j.clgc.2014.12.004DOI Listing
June 2015

Sequential use of the androgen synthesis inhibitors ketoconazole and abiraterone acetate in castration-resistant prostate cancer and the predictive value of circulating androgens.

Clin Cancer Res 2014 Dec 21;20(24):6269-76. Epub 2014 Oct 21.

Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California.

Purpose: Patients previously treated with ketoconazole were excluded from phase III trials of abiraterone acetate due to potential overlapping mechanism of action. The purpose of this study was to determine the clinical utility of abiraterone and its impact on circulating androgens following ketoconazole.

Experimental Design: Chemotherapy-naïve patients with progressive metastatic castration-resistant prostate cancer (mCRPC) and prior ketoconazole therapy ≥28 days received abiraterone acetate 1,000 mg daily and prednisone 5 mg twice daily. The primary endpoint was the proportion of patients with PSA response, defined as ≥30% PSA decline at 12 weeks. H0 = 0.30 versus H1 = 0.50 (α = 0.05, power = 0.83). Circulating androgen levels were measured using liquid chromatography tandem mass spectrometry.

Results: Thirty-nine patients were included in the final analysis. Twenty (51%; 95% confidence interval, 36%-66%) patients had ≥30% PSA decline; the null hypothesis was rejected. Sixteen (41%) had ≥50% PSA decline. Median PFS (progression-free survival) was 16 weeks; median radiographic PFS (rPFS) was 36 weeks. Samples for measurement of baseline androgens were available in 37 patients. The PSA response proportion was 59% in 29 patients with DHEA ≥ limit of quantitation (LOQ), compared with 13% in 8 patients with DHEA < LOQ (P = 0.042). Median PFS was 6 and 16 weeks in DHEA < LOQ and DHEA ≥ LOQ patients, respectively (P = 0.017); median rPFS was 14 and 36 weeks in DHEA < LOQ and DHEA ≥ LOQ patients, respectively (P < 0.001).

Conclusions: Abiraterone demonstrates modest clinical efficacy in mCRPC patients previously treated with ketoconazole. Patients with DHEA ≥ LOQ were more likely to demonstrate PSA responses and longer PFS. Analysis of circulating androgens merits further investigation as a biomarker for response to androgen synthesis inhibitor therapy.
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http://dx.doi.org/10.1158/1078-0432.CCR-14-1595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277885PMC
December 2014

Intestinal tumor suppression in ApcMin/+ mice by prostaglandin D2 receptor PTGDR.

Cancer Med 2014 Aug 12;3(4):1041-51. Epub 2014 Apr 12.

Department of Pediatrics, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, California.

Our earlier work showed that knockout of hematopoietic prostaglandin D synthase (HPGDS, an enzyme that produces prostaglandin D2) caused more adenomas in Apc(Min/+) mice. Conversely, highly expressed transgenic HPGDS allowed fewer tumors. Prostaglandin D2 (PGD2) binds to the prostaglandin D2 receptor known as PTGDR (or DP1). PGD2 metabolites bind to peroxisome proliferator-activated receptor γ (PPARG). We hypothesized that Ptgdr or Pparg knockouts may raise numbers of tumors, if these receptors take part in tumor suppression by PGD2. To assess, we produced Apc(Min/+) mice with and without Ptgdr knockouts (147 mice). In separate experiments, we produced Apc(Min/+) mice expressing transgenic lipocalin-type prostaglandin D synthase (PTGDS), with and without heterozygous Pparg knockouts (104 mice). Homozygous Ptgdr knockouts raised total numbers of tumors by 30-40% at 6 and 14 weeks. Colon tumors were not affected. Heterozygous Pparg knockouts alone did not affect tumor numbers in Apc(Min/+) mice. As mentioned above, our Pparg knockout assessment also included mice with highly expressed PTGDS transgenes. Apc(Min/+) mice with transgenic PTGDS had fewer large adenomas (63% of control) and lower levels of v-myc avian myelocytomatosis viral oncogene homolog (MYC) mRNA in the colon. Heterozygous Pparg knockouts appeared to blunt the tumor-suppressing effect of transgenic PTGDS. However, tumor suppression by PGD2 was more clearly mediated by receptor PTGDR in our experiments. The suppression mechanism did not appear to involve changes in microvessel density or slower proliferation of tumor cells. The data support a role for PGD2 signals acting through PTGDR in suppression of intestinal tumors.
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http://dx.doi.org/10.1002/cam4.251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4303173PMC
August 2014

A phase II study of insulin-like growth factor receptor inhibition with nordihydroguaiaretic acid in men with non-metastatic hormone-sensitive prostate cancer.

Oncol Rep 2012 Jan 4;27(1):3-9. Epub 2011 Oct 4.

Genitourinary Medical Oncology Program, Biostatistics and Computational Biology Core, Helen Diller Family Comprehensive Cancer Center, Department of Bioengineering and Therapeutic Sciences, Box 1711, 1600 Divisadaro Street, University of California, San Francisco, San Francisco, CA 94115-1711, USA.

Insulin-like growth factor (IGF)-mediated signaling is a newly recognized clinical target in prostate cancer, and it is hypothesized that blockade of the IGF receptor (IGF1R) will impair downstream signaling and slow tumor growth. In this study the efficacy of nordihydroguaiaretic acid (NDGA), a small molecule inhibitor of the IGF-1R, was prospectively evaluated in patients with non-metastatic hormone-sensitive prostate cancer (HSPC). Eligible patients had non-metastatic HSPC with a rising prostate-specific antigen (PSA) and a normal testosterone level. NDGA 2000 mg was given orally daily in 28 day cycles and treatment continued until PSA progression or toxicity. Accrual was stopped early after a pre-planned interim analysis showed no significant PSA declines after 3 cycles of treatment among the first 12 patients enrolled. Median time on treatment was 9 cycles (range 2-19) for 11 patients now off study; 1 patient continues to receive therapy and has been on study for 29 months. Seven patients experienced non-sustained declines in PSA ranging from 1.9 to 15.8% of baseline. PSADT lengthened by a median of 1.4 months for all evaluable patients when compared to pretreatment PSADT (range -6.1 to +19.8 months). Grade 3 events were rare and included nausea/vomiting, syncope due to dehydration, and elevated liver function tests in 1 patient, and cognitive disturbance in another patient. NDGA therapy lengthens median PSADT but does not induce significant PSA declines. Further study may require a placebo-control to determine if changes in PSADT are drug related.
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http://dx.doi.org/10.3892/or.2011.1487DOI Listing
January 2012

Hematopoietic prostaglandin D synthase (HPGDS): a high stability, Val187Ile isoenzyme common among African Americans and its relationship to risk for colorectal cancer.

Prostaglandins Other Lipid Mediat 2012 Jan 28;97(1-2):22-8. Epub 2011 Jul 28.

Division of Medical Genetics, Harbor-UCLA Medical Center and Los Angeles Biomedical Research Institute, Torrance, CA, USA.

Intestinal tumors in Apc(Min/+) mice are suppressed by over-production of HPGDS, which is a glutathione transferase that forms prostaglandin D(2) (PGD(2)). We characterized naturally occurring HPGDS isoenzymes, to see if HPGDS variation is associated with human colorectal cancer risk. We used DNA heteroduplex analysis and sequencing to identify HPGDS variants among healthy individuals. HPGDS isoenzymes were produced in bacteria, and their catalytic activities were tested. To determine in vivo effects, we conducted pooled case-control analyses to assess whether there is an association of the isoenzyme with colorectal cancer. Roughly 8% of African Americans and 2% of Caucasians had a highly stable Val187lle isoenzyme (with isoleucine instead of valine at position 187). At 37°C, the wild-type enzyme lost 15% of its activity in 1h, whereas the Val187Ile form remained >95% active. At 50°C, the half life of native HPGDS was 9min, compared to 42 min for Val187Ile. The odds ratio for colorectal cancer among African Americans with Val187Ile was 1.10 (95% CI, 0.75-1.62; 533 cases, 795 controls). Thus, the Val187Ile HPGDS isoenzyme common among African Americans is not associated with colorectal cancer risk. Other approaches will be needed to establish a role for HPGDS in occurrence of human intestinal tumors, as indicated by a mouse model.
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http://dx.doi.org/10.1016/j.prostaglandins.2011.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3226866PMC
January 2012

A phase 1 study of everolimus and sorafenib for metastatic clear cell renal cell carcinoma.

Cancer 2011 Sep 8;117(18):4194-200. Epub 2011 Mar 8.

Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California at San Francisco, San Francisco, California 94143-1711, USA.

Background: The current study was conducted to assess the maximum tolerated dose (MTD), safety, pharmacokinetics, and preliminary antitumor effect of everolimus, a mammalian target of rapamycin inhibitor, in combination with sorafenib, a tyrosine kinase inhibitor, in patients with metastatic clear cell renal cell carcinoma.

Methods: Sequential cohorts of patients received escalating doses of everolimus and sorafenib in 28-day cycles in the absence of a dose-limiting toxicity (DLT) or disease progression were examined.

Results: Twenty patients with a median age of 65 years received therapy in 3 cohorts. Dose level 1 was comprised of everolimus at a dose of 2.5 mg daily and sorafenib at a dose of 400 mg twice daily (6 patients), dose level 2 was comprised of everolimus at a dose of 5 mg daily and sorafenib at a dose of 400 mg twice daily (8 patients), and dose level 3 was comprised of everolimus at a dose of 10 mg daily and sorafenib at a dose of 200 mg twice daily (6 patients). DLTs included grade 4 (according to National Cancer Institute Common Terminology Criteria for Adverse Events [version 3.0]) hyperuricemia with grade 2 gout and grade 3 lipase associated with grade 2 pancreatitis at dose level 2, and grade 3 rash in 2 patients at dose level 3. Dose level 2 (everolimus at a dose of 5 mg daily and sorafenib at a dose of 400 mg twice daily) was established as the maximum tolerated dose. Treatment-related adverse events occurring in >20% of patients included diarrhea, hand-foot syndrome, hypertension, hypophosphatemia, hypothyroidism, and rash. Five of 20 patients achieved Response Evaluation Criteria In Solid Tumors (RECIST)-defined partial responses, all of which occurred in patients without a history of prior systemic therapy. Seven of 8 patients treated at dose level 2 experienced a partial response or stable disease. Pharmacokinetic analysis revealed no interaction between everolimus and sorafenib.

Conclusions: The combination of everolimus and sorafenib was associated with acceptable toxicity and evidence of antitumor activity in previously untreated patients with metastatic renal cell carcinoma.
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http://dx.doi.org/10.1002/cncr.25931DOI Listing
September 2011

Tumor fistulization associated with targeted therapy: computed tomographic findings and clinical consequences.

J Comput Assist Tomogr 2011 Jan-Feb;35(1):86-90

Department of Radiology, University of California San Francisco, San Francisco, CA 94143-0628, USA.

Purpose: To describe the computed tomographic (CT) appearances and clinical consequences of tumor fistulization as a complication of targeted therapy for cancer.

Methods: The committee on human research approved this Health Insurance Portability and Accountability Act-compliant study and waived written informed consent. Based on the records of the senior author and our multidisciplinary Tumor Boards, we retrospectively identified 4 patients (1 man and 3 women with a mean age of 55.25 years; range, 47 to 64 years) who developed tumor fistulization while being treated with targeted therapy consisting of sunitinib (n = 2); bevacizumab (n = 1); and XL184, an investigational c-Met inhibitor (n = 1). All available clinical, imaging, and histopathological records were reviewed, with particular emphasis on treatment administered, CT findings, and clinical course.

Results: All 4 patients developed fistulae from large metastatic deposits in the abdomen (mean size before treatment, 10.55 cm; range, 7.4-13.4 cm) to the gastrointestinal tract, and one patient also developed fistulae from a lung metastasis of undetermined size to the bronchial tree. All fistulae manifested as the appearance of air within a pre-existing tumor mass. At the time of fistula detection, disease at other sites in the 4 patients showed signs of regression (n = 1), progression (n = 2), or stability (n = 1). Currently, one patient is alive without evidence of disease, and the 3 other patients are deceased.

Conclusions: Targeted therapy can be associated with tumor fistulization to the gastrointestinal tract or tracheobronchial tree; familiarity with the CT findings should facilitate the diagnosis of this complication, which seems to be of variable and patient-specific prognostic significance.
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http://dx.doi.org/10.1097/RCT.0b013e3181fce2cbDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3675219PMC
March 2011

Effect of the somatostatin analog octreotide acetate on circulating insulin-like growth factor-1 and related peptides in patients with non-metastatic castration-resistant prostate cancer: results of a phase II study.

Urol Oncol 2012 Jul-Aug;30(4):408-14. Epub 2010 Oct 2.

Urologic Oncology Program, Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA 94143, USA.

Background: Insulin-like growth factor (IGF) mediated signaling has been implicated in the growth of many tumor types including prostate cancer, and it is hypothesized that lowering circulating IGF levels in men with castration resistant prostate cancer (CRPC) will slow tumor growth. In this study, the efficacy of depot octreotide acetate was prospectively evaluated in patients with CRPC.

Methods: Eligible patients had progressive non-metastatic CRPC. Octreotide acetate 30 mg was administered intramuscularly every 28 days. Changes in PSA, IGF-1, IGF-2, IGF binding protein-1 (IGFBP-1), and IGFBP-3 were evaluated over time.

Results: Accrual was stopped early after a pre-planned interim analysis showed no prostate specific antigen (PSA) declines after 3 cycles of treatment among the first 13 patients enrolled. Median baseline PSA and IGF-1 measurements were 36.2 ng/ml and 162.6 ng/ml, respectively, and median time on treatment was 13 weeks. Radiographic progression occurred in 7 patients, PSA-only progression occurred in 5 patients, and 1 patient was taken off the study due to a grade 3 drug interaction. After 3 cycles of treatment IGF-1 significantly declined with a median -34.5% (P = 0.01) and IGFBP-1 significantly increased with a median 76.3% (P = 0.046). IGF-2 and IGFBP-3 were not significantly changed from baseline.

Conclusions: Octreotide acetate significantly lowers IGF-1 and raises IGFBP-1 levels in patients with non-metastatic CRPC, but does not result in sustained declines in PSA. While treatment with single-agent octreotide may not be warranted, its inclusion in combination regimens directly targeting the IGF-1 receptor on tumor cells may be of interest.
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http://dx.doi.org/10.1016/j.urolonc.2010.06.014DOI Listing
November 2012

Asymptomatic maternal combined homocystinuria and methylmalonic aciduria (cblC) detected through low carnitine levels on newborn screening.

J Pediatr 2009 Dec;155(6):924-7

Division of Medical Genetics, Harbor-UCLA Medical Center, Torrance, CA 90502, USA.

A symptom-free woman gave birth to a girl with a low carnitine level on newborn screening. The baby was unaffected, but the mother had biochemical abnormalities and mutations characteristic of the cblC defect of vitamin B(12) metabolism (late-onset form). This patient with cblC was detected through her infant's newborn screening.
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http://dx.doi.org/10.1016/j.jpeds.2009.06.046DOI Listing
December 2009

Potentiating endogenous antitumor immunity to prostate cancer through combination immunotherapy with CTLA4 blockade and GM-CSF.

Cancer Res 2009 Jan;69(2):609-15

Division of Hematology/Oncology, University of California, San Francisco, San Francisco, California 94143, USA.

CTL-associated antigen 4 (CTLA4) is a costimulatory molecule expressed on activated T cells that delivers an inhibitory signal to these T cells. CTLA4 blockade with antibody treatment has been shown to augment antitumor immunity in animal models and is being developed as a treatment for cancer patients. As has been seen in preclinical models, combining CTLA4 blockade and granulocyte macrophage colony-stimulating factor (GM-CSF)-based immunotherapies can enhance the antitumor efficacy of this approach. We therefore examined whether CTLA4 blockade could be combined with GM-CSF administration. We treated 24 patients with metastatic, castration-resistant prostate cancer in a phase I trial where sequential cohorts were treated with increasing doses of ipilimumab, a fully human anti-CTLA4 antibody. Study subjects also received s.c. injections of GM-CSF at a fixed dose. Of the six patients treated at the highest dose level, three had confirmed PSA declines of >50%, including one patient that had a partial response in visceral metastases. Expansion of activated, circulating CD25(+) CD69(+) CD8(+) T cells occurred more frequently at higher doses of treatment and was greater in magnitude than was seen in patients who received the same doses of either ipilimumab or GM-CSF alone. By screening sera with protein arrays, we showed that our treatment can induce antibody responses to NY-ESO-1. These results show that this combination immunotherapy can induce the expansion not only of activated effector CD8 T cells in vivo but also of T cells that are specific for known tumor-associated antigens from the endogenous immune repertoire.
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http://dx.doi.org/10.1158/0008-5472.CAN-08-3529DOI Listing
January 2009

Management of hormone refractory prostate cancer.

Curr Opin Support Palliat Care 2007 Oct;1(3):187-91

UCSF Comprehensive Cancer Center, University of California, San Francisco, California 94115, USA.

Purpose Of Review: This review highlights the most interesting developments and outstanding issues surrounding the management of hormone-refractory prostate cancer published in the medical literature during the past year.

Recent Findings: Recent research has reported poor health-related quality-of-life outcomes for patient with hormone-refractory prostate cancer treated in standard clinical practices. In addition, age-related differences in survival appear to exist for patients with hormone-refractory prostate cancer. Two potential future therapies for hormone-refractory prostate cancer, sipuleucel-T and the combination regimen of docetaxel and DN-101, demonstrate promising preliminary clinical data in terms of improving survival while minimizing toxicity. A variety of novel agents has been tested for hormone-refractory prostate cancer, including pertuzumab and BMS-275291, which may stabilize disease with minimal toxicity. In terms of bone-related health, skeletal-related events have been found to be associated with worse survival and health-related quality of life outcomes.

Summary: Data reported during the past year have implications for future research directions. This direction includes the need for continued exploration of health-related quality of life and age-related outcomes, further study of the disease-stabilizing effects of novel therapies and their translation into improved survival, as well as directed efforts to continue preventing skeletal-related events, which may impact survival and health-related quality of life.
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http://dx.doi.org/10.1097/SPC.0b013e3282efd689DOI Listing
October 2007

Prostate cancer update: 2007.

Curr Opin Oncol 2008 May;20(3):294-9

UCSF Comprehensive Cancer Center, University of California, San Francisco, California 94115, USA.

Purpose Of Review: The present review highlights the year's most important developments in the risk assessment, diagnosis, and treatment of prostate cancer.

Recent Findings: Recent research has helped define the prognostic importance of incorporating tertiary Gleason 5 pattern into the Gleason sum as well as interpretation of prostate-specific antigen levels when patients are being treated with low doses of finasteride. More data have emerged on the benefits of active treatment in elderly men newly diagnosed with localized prostate cancer. Particular subgroups of high-risk postprostatectomy patients (low postsurgical prostate-specific antigen level, positive surgical margins) may benefit from adjuvant radiotherapy. For salvage radiotherapy, the first comprehensive nomogram has been developed. Further data is emerging on the cardiovascular risks associated with androgen deprivation therapy even when administered for shorter treatment durations in conjunction with definitive local therapy. In addition, androgen deprivation therapy may be associated with earlier incidence of fatal cardiovascular events. For advanced prostate cancer, the first prospective trial defining taxane-resistant prostate cancer is described.

Summary: The data of the present year have important implications in the diagnosis and management of prostate cancer by urologists, radiation oncologists, and medical oncologists.
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http://dx.doi.org/10.1097/CCO.0b013e3282f8b075DOI Listing
May 2008

A phase I trial of docetaxel/estramustine/imatinib in patients with hormone-refractory prostate cancer.

Clin Genitourin Cancer 2007 Jun;5(5):323-8

UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94115, USA.

Background: Docetaxel/estramustine was a commonly used regimen to treat metastatic hormone-refractory prostate cancer. Imatinib inhibits the platelet-derived growth factor receptor that is expressed in prostate cancer and is synergistic with taxanes in preclinical prostate cancer models.

Patients And Methods: A phase I trial of docetaxel/estramustine/ imatinib was undertaken to determine the safety and maximum tolerated dose of this combination. Patients with progressive, metastatic, hormone-refractory prostate cancer were treated every 21 days with fixed doses of estramustine (280 mg orally 3 times a day on days 1-5), imatinib (400 mg orally daily on days 1-21), dexamethasone (8 mg orally twice daily on days 1-3), and prophylactic warfarin (2 mg orally daily on days 1-21). Cohorts of 3-6 patients were enrolled to receive escalating doses of docetaxel on day 2 from 50 mg/m2 to 60 mg/m2 to 70 mg/m2. Thirteen patients were treated.

Results: On dose level 3 (docetaxel 70 mg/m2 and imatinib 400 mg daily), 2 patients experienced grade 3 elevations in prothrombin time, attributed to the interaction between imatinib and warfarin. The protocol was amended to include an intermediate dose level (docetaxel 60 mg/m2 and imatinib 300 mg daily). However, in the overall study, there were 5 unacceptable toxicities (2 cerebrovascular accidents, 1 myocardial infarction, 1 mesenteric ischemia, and 1 deep venous thrombosis) in 13 patients; 2 of those toxicities resulted in death. The study was closed early to further accrual.

Conclusion: The high incidence of thromboembolic events observed when imatinib was combined with docetaxel/estramustine precludes further exploration of this regimen.
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http://dx.doi.org/10.3816/CGC.2007.n.011DOI Listing
June 2007

Prostate cancer update: 2006.

Curr Opin Oncol 2007 May;19(3):229-33

UCSF Comprehensive Cancer Center, University of California, San Francisco, California 94115, USA.

Purpose Of Review: This review highlights the most important developments in the diagnosis, prevention, and treatment of prostate cancer published in the medical literature over the past year.

Recent Findings: Recent research has revealed a relatively high rate of prostate specific antigen screening in elderly men regardless of comorbidity status. Other findings include data that finasteride may increase the sensitivity of prostate specific antigen to detect prostate cancer. In terms of use of androgen deprivation therapy as part of primary therapy, a randomized trial has demonstrated that immediate therapy for locally advanced prostate cancer improves overall survival. There is growing literature, however, confirming the risks associated with this treatment, including an increased incidence of cardiovascular events and diabetes. New randomized trial data of adjuvant radiotherapy for high-risk disease have not demonstrated a survival benefit over observation. For patients who experience disease relapse following local therapy, definitions of biochemical failure following prostatectomy and radiation therapy are proposed. In more advanced disease, immunotherapy has preliminarily demonstrated survival benefit in a randomized trial.

Summary: Data reported over the last year have significant implications for those involved in the management of prostate cancer, ranging from primary care physicians to medical oncologists, urologists, and radiation oncologists.
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http://dx.doi.org/10.1097/CCO.0b013e3280ad43bdDOI Listing
May 2007

Intermittent chemotherapy for metastatic hormone refractory prostate cancer.

Crit Rev Oncol Hematol 2007 Mar 11;61(3):243-54. Epub 2006 Dec 11.

UCSF Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA 94115, USA.

While docetaxel/prednisone chemotherapy has demonstrated a survival advantage in metastatic hormone refractory prostate cancer (HRPC) patients, the optimal duration of chemotherapy has not yet been established. Currently, a standard practice is to treat patients indefinitely until unacceptable toxicity or disease progression. A systematic approach to providing breaks in treatment schedules (intermittent chemotherapy) for patients who experience an initial response to chemotherapy may avoid or delay the development of progressive toxicity. Whether continuous therapy offers an advantage over intermittent therapy, in terms of balancing disease control and overall survival with treatment-related toxicities and quality-of-life (QOL) is yet unanswered. This article will: (1) review the data from prior studies of intermittent versus continuous chemotherapy in other solid tumors, (2) review existing trials of intermittent chemotherapy in prostate cancer, (3) discuss intermittent chemotherapy clinical trial design considerations, and (4) discuss the future role of intermittent chemotherapy for the treatment of prostate cancer.
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http://dx.doi.org/10.1016/j.critrevonc.2006.10.002DOI Listing
March 2007

Immunotherapy for prostate cancer using prostatic acid phosphatase loaded antigen presenting cells.

Urol Oncol 2006 Sep-Oct;24(5):434-41

Department of Medicine, University of California, San Francisco, San Francisco, CA 94115, USA.

Dendritic cells from patients with cancer are deficient in number and functional activity, leading to inadequate tumor immunosurveillance as a result of poor induction of T-cell antitumor responses. Loaded dendritic cell therapy is a vaccination strategy aimed at eliciting tumor antigen-specific, T-cell immune responses. Loaded dendritic cell therapy using prostatic acid phosphatase (APC8015; Provenge, Dendreon Corp., Seattle, WA) as an immunogen has shown a survival benefit in patients with metastatic hormone-refractory prostate cancer in a randomized phase III trial. This review will summarize the prostate cancer clinical trials using APC8015 and discuss the potential future role of APC8015 in prostate cancer treatment.
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http://dx.doi.org/10.1016/j.urolonc.2005.08.010DOI Listing
December 2006

A phase II trial of imatinib mesylate in patients with biochemical relapse of prostate cancer after definitive local therapy.

BJU Int 2006 Oct;98(4):763-9

University of California/San Francisco, San Francisco, CA 94115, USA.

Objective: To determine the biological effects of imatinib mesylate (STI-571, Gleevec; Novartis Pharmaceuticals, Inc., East Hanover, NJ, USA), as measured by prostate-specific antigen (PSA) kinetics in men with biochemical relapse of prostate cancer after definitive local therapy.

Patients And Methods: Men with prostate cancer, who had had definitive local therapy, with nonmetastatic recurrent disease as manifested by a rising PSA level, were enrolled on this phase II trial. Men received 400 mg of imatinib mesylate orally twice daily and continuously until disease progression or unacceptable toxicity. The PSA level was measured monthly.

Results: In all, 20 men with biochemically relapsed prostate cancer were treated. The median pretreatment PSA level was 5.4 ng/mL. Of the 19 evaluable men, one achieved a >or= 50% reduction in PSA level and two had decreases of <50%. For the 16 men in whom the on-treatment PSA doubling time (PSADT) could be calculated (those with increasing PSA level) the median PSADT did not increase significantly (5.8 vs 7.2 months, P = 0.64). Eleven of 20 men discontinued therapy due to toxicity and the trial was stopped early due to toxicity.

Conclusions: Based on the lack of PSA modulation and pronounced toxicities leading to early closure of this trial, further study of single-agent imatinib mesylate at this dose (400 mg twice daily) cannot be recommended in this patient population.
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http://dx.doi.org/10.1111/j.1464-410X.2006.06396.xDOI Listing
October 2006

Angiogenesis inhibition plus chemotherapy for metastatic hormone refractory prostate cancer: history and rationale.

Urol Oncol 2006 May-Jun;24(3):250-3

Urologic Oncology Program, UCSF Comprehensive Cancer Center, University of California-San Francisco, San Francisco, CA 94143, USA.

Angiogenesis inhibition with bevacizumab and other agents of this class are showing significant activity in a variety of cancers. In prostate cancer, the single agent activity has been low, but the addition of these agents to chemotherapy may be the area in which they provide their greatest clinical benefit. An ongoing study conducted by the Cancer and Leukemia Group B will test this approach in men with metastatic hormone refractory prostate cancer. Future studies may test the efficacy of anti-angiogenic strategies in earlier stage disease as well as in combination with other approaches. This review will highlight the clinical experience to date with angiogenesis inhibitors in prostate cancer and the ongoing studies.
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http://dx.doi.org/10.1016/j.urolonc.2005.11.021DOI Listing
October 2006

Clinical trials in patients with biochemically relapsed prostate cancer.

BJU Int 2006 May;97(5):905-10

UCSF Comprehensive Cancer Center, University of California/San Francisco, San Francisco, CA 94115, USA.

In this section there is a wide diversity of mini-reviews, covering several areas of interest for readers. Authors from the USA write about clinical trials in patients with biochemically relapsed prostate cancer, again bridging the divide between medical oncologists and urologists who specialise in urological oncological surgery. The second paper is a joint one from Germany and the USA, bringing the reader up to date with advances in the treatment of stress urinary incontinence. Finally there are two papers from Australia describing the use of positron emission tomography in renal cancer and in prostate cancer.
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http://dx.doi.org/10.1111/j.1464-410X.2006.06124.xDOI Listing
May 2006