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Leonard N Chen,
Simeng Suy,
Sunghae Uhm,
Eric K Oermann,
Andrew W Ju,
Viola Chen,
Heather N Hanscom,
Sarah Laing,
Joy S Kim,
Siyuan Lei, [......],
Gaurav Bandi,
John Pahira,
Kevin G McGeagh,
Brian T Collins,
Pranay Krishnan, Nancy A Dawson,
Kathryn L Taylor,
Anatoly Dritschilo,
John H Lynch,
Sean P Collins
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ABSTRACT: BACKGROUND: Stereotactic body radiation therapy (SBRT) delivers fewer high-dose fractions of radiation which may be radiobiologically favorable to conventional low-dose fractions commonly used for prostate cancer radiotherapy. We report our early experience using SBRT for localized prostate cancer. METHODS: Patients treated with SBRT from June 2008 to May 2010 at Georgetown University Hospital for localized prostate carcinoma, with or without the use of androgen deprivation therapy (ADT), were included in this retrospective review of data that was prospectively collected in an institutional database. Treatment was delivered using the CyberKnife(R) with doses of 35 Gy or 36.25 Gy in 5 fractions. Biochemical control was assessed using the Phoenix definition. Toxicities were recorded and scored using the CTCAE v.3. Quality of life was assessed before and after treatment using the Short Form-12 Health Survey (SF-12), the American Urological Association Symptom Score (AUA) and Sexual Health Inventory for Men (SHIM) questionnaires. Late urinary symptom flare was defined as an AUA score >= 15 with an increase of >= 5 points above baseline six months after the completion of SBRT. RESULTS: One hundred patients (37 low-, 55 intermediate- and 8 high-risk according to the D'Amico classification) at a median age of 69 years (range, 48--90 years) received SBRT, with 11 patients receiving ADT. The median pre-treatment prostate-specific antigen (PSA) was 6.2 ng/ml (range, 1.9-31.6 ng/ml) and the median follow-up was 2.3 years (range, 1.4-3.5 years). At 2 years, median PSA decreased to 0.49 ng/ml (range, 0.1-1.9 ng/ml). Benign PSA bounce occurred in 31% of patients. There was one biochemical failure in a high-risk patient, yielding a two-year actuarial biochemical relapse free survival of 99%. The 2-year actuarial incidence rates of GI and GU toxicity >= grade 2 were 1% and 31%, respectively. A median baseline AUA symptom score of 8 significantly increased to 11 at 1 month (p = 0.001), however returned to baseline at 3 months (p = 0.60). Twenty one percent of patients experienced a late transient urinary symptom flare in the first two years following treatment. Of patients who were sexually potent prior to treatment, 79% maintained potency at 2 years post-treatment. CONCLUSIONS: SBRT for clinically localized prostate cancer was well tolerated, with an early biochemical response similar to other radiation therapy treatments. Benign PSA bounces were common. Late GI and GU toxicity rates were comparable to conventionally fractionated radiation therapy and brachytherapy. Late urinary symptom flares were observed but the majority resolved with conservative management. A high percentage of men who were potent prior to treatment remained potent two years following treatment.
Radiation Oncology 03/2013; 8(1):58. · 2.32 Impact Factor
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Tanya B Dorff,
Thomas W Flaig,
Catherine M Tangen,
Maha H A Hussain,
Gregory P Swanson,
David P Wood,
Wael A Sakr, Nancy A Dawson,
Naomi B Haas,
E David Crawford,
Nicholas J Vogelzang,
Ian M Thompson,
L Michael Glode
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ABSTRACT: Men with high-risk features (extraprostatic extension or high Gleason grade) face a high risk of prostate cancer recurrence after radical prostatectomy. Clinical trials of adjuvant systemic therapy for such patients have been limited.
The SWOG (Southwest Oncology Group) S9921 study randomly assigned 983 men with high-risk features at prostatectomy to receive adjuvant therapy with androgen deprivation (ADT) alone or in combination with mitoxantrone chemotherapy. ADT consisted of goserelin and bicalutamide for 2 years.
Although the final primary treatment comparison results are not ready for publication, this article reports results in the ADT-alone control arm with a median follow-up of 4.4 years. For these 481 men, the estimated 5-year biochemical failure-free survival is 92.5% (95% CI, 90 to 95), and 5-year overall survival is 95.9% (95% CI, 93.9 to 97.9).
The results of this trial, taken in context, make a compelling argument for counseling all high-risk patients with prostate cancer about adjuvant ADT. This article discusses the challenges in the design and implementation of clinical trials to take the next step forward in adjuvant therapy for prostate cancer because of the excellent survival achieved with currently available therapies and highlights the need for better molecular markers to personalize care.
Journal of Clinical Oncology 05/2011; 29(15):2040-5. · 18.37 Impact Factor
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ABSTRACT: Prostate cancer represents a third of all newly diagnosed cancers in men in the USA with an estimated incidence of 192,280 cases and 27,360 deaths in 2009. It continues to be a major cause of cancer-related morbidity and mortality, and there is an urgent need for new treatments. Historically, systemic therapy options were limited after progression on docetaxel-based chemotherapy. This article reviews current data on the novel therapeutics demonstrating activity in metastatic castration-resistant prostate cancer and their future role in the treatment of this disease with a poor prognosis.
Future Oncology 04/2011; 7(4):551-8. · 3.16 Impact Factor
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Eric K Oermann,
Simeng Suy,
Heather N Hanscom,
Joy S Kim,
Sue Lei,
Xia Yu,
Guowei Zhang,
Brook Ennis,
Joyann P Rohan,
Nathaniel Piel, [......],
Gaurav Bandi,
John Pahira,
Kevin G McGeagh,
Lucile Adams-Campbell,
Reena Jha, Nancy A Dawson,
Brian T Collins,
Anatoly Dritschilo,
John H Lynch,
Sean P Collins
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ABSTRACT: The CyberKnife is an appealing delivery system for hypofractionated stereotactic body radiation therapy (SBRT) because of its ability to deliver highly conformal radiation therapy to moving targets. This conformity is achieved via 100s of non-coplanar radiation beams, which could potentially increase transitory testicular irradiation and result in post-therapy hypogonadism. We report on our early experience with CyberKnife SBRT for low- to intermediate-risk prostate cancer patients and assess the rate of inducing biochemical and clinical hypogonadism.
Twenty-six patients were treated with hypofractionated SBRT to a dose of 36.25 Gy in 5 fractions. All patients had histologically confirmed low- to intermediate-risk prostate adenocarcinoma (clinical stage ≤ T2b, Gleason score ≤ 7, PSA ≤ 20 ng/ml). PSA and total testosterone levels were obtained pre-treatment, 1 month post-treatment and every 3 months thereafter, for 1 year. Biochemical hypogonadism was defined as a total serum testosterone level below 8 nmol/L. Urinary and gastrointestinal toxicity was assessed using Common Toxicity Criteria v3; quality of life was assessed using the American Urological Association Symptom Score, Sexual Health Inventory for Men and Expanded Prostate Cancer Index Composite questionnaires.
All 26 patients completed the treatment with a median 15 months (range, 13-19 months) follow-up. Median pre-treatment PSA was 5.75 ng/ml (range, 2.3-10.3 ng/ml), and a decrease to a median of 0.7 ng/ml (range, 0.2-1.8 ng/ml) was observed by one year post-treatment. The median pre-treatment total serum testosterone level was 13.81 nmol/L (range, 5.55 - 39.87 nmol/L). Post-treatment testosterone levels slowly decreased with the median value at one year follow-up of 10.53 nmol/L, significantly lower than the pre-treatment value (p < 0.013). The median absolute fall was 3.28 nmol/L and the median percent fall was 23.75%. There was no increase in biochemical hypogonadism at one year post-treatment. Average EPIC sexual and hormonal scores were not significantly changed by one year post-treatment.
Hypofractionated SBRT offers the radiobiological benefit of a large fraction size and is well-tolerated by men with low- to intermediate-risk prostate cancer. Early results are encouraging with an excellent biochemical response. The rate of new biochemical and clinical hypogonadism was low one year after treatment.
Journal of Hematology & Oncology 03/2011; 4:12. · 3.99 Impact Factor
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ABSTRACT: To report the final analysis of a Phase II trial, which investigated the safety and efficacy of the specific endothelin A receptor antagonist zibotentan (AstraZeneca, Macclesfield, UK) in patients with metastatic castration-resistant prostate cancer (CRPC).
Patients with CRPC and bone metastases who were pain free or mildly symptomatic for pain were randomized to receive once-daily oral tablets of zibotentan 10 mg, 15 mg or placebo. The primary endpoint was the time to progression and secondary endpoints included overall survival, change in the number of bone metastases, and safety.
In total, 312 patients were randomized (placebo, n= 107; zibotentan 10 mg, n= 107; zibotentan 15 mg, n= 98). The median duration of study treatment and median follow-up time were 4 and 22 months, respectively. At the final analysis, there were no statistical differences of the primary outcome of time to progression between treatment groups, although an improvement in overall survival was observed in the zibotentan groups compared to placebo. Consistent with the previous analyses for overall survival, hazard ratios (HRs) of less than one were sustained for both zibotentan 15 mg (HR, 0.76; 80% CI, 0.61-0.94; P= 0.103) and 10 mg (HR, 0.83; 80% CI, 0.67-1.02; P= 0.254). The most commonly reported adverse events considered to be related to zibotentan treatment were peripheral oedema, headache and nasal congestion.
The results obtained in the present study support endothelin A receptor antagonism as an approach for treating patients with CRPC. To confirm the survival signal observed in the present study, zibotentan is being investigated further in the ENdoTHelin A USE (ENTHUSE) Phase III clinical trial programme.
BJU International 10/2010; 106(7):966-73. · 2.84 Impact Factor
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Eric K Oermann,
Rebecca S Slack,
Heather N Hanscom,
Sue Lei,
Simeng Suy,
Hyeon U Park,
Joy S Kim,
Benjamin A Sherer,
Brian T Collins,
Andrew N Satinsky, [......],
Stephen W Dejter,
William C Maxted,
James B Regan,
John J Pahira,
Kevin G McGeagh,
Reena C Jha, Nancy A Dawson,
Anatoly Dritschilo,
John H Lynch,
Sean P Collins
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ABSTRACT: Clinical data suggest that large radiation fractions are biologically superior to smaller fraction sizes in prostate cancer radiotherapy. The CyberKnife is an appealing delivery system for hypofractionated radiosurgery due to its ability to deliver highly conformal radiation and to track and adjust for prostate motion in real-time. We report our early experience using the CyberKnife to deliver a hypofractionated stereotactic body radiation therapy (SBRT) boost to patients with intermediate- to high-risk prostate cancer. Twenty-four patients were treated with hypofractionated SBRT and supplemental external radiation therapy plus or minus androgen deprivation therapy (ADT). Patients were treated with SBRT to a dose of 19.5 Gy in 3 fractions followed by intensity modulated radiation therapy (IMRT) to a dose of 50.4 Gy in 28 fractions. Quality of life data were collected with American Urological Association (AUA) symptom score and Expanded Prostate Cancer Index Composite (EPIC) questionnaires before and after treatment. PSA responses were monitored; acute urinary and rectal toxicities were assessed using Common Toxicity Criteria (CTC) v3. All 24 patients completed the planned treatment with an average follow-up of 9.3 months. For patients who did not receive ADT, the median pre-treatment PSA was 10.6 ng/ml and decreased in all patients to a median of 1.5 ng/ml by 6 months post-treatment. Acute effects associated with treatment included Grade 2 urinary and gastrointestinal toxicity but no patient experienced acute Grade 3 or greater toxicity. AUA and EPIC scores returned to baseline by six months post-treatment. Hypofractionated SBRT combined with IMRT offers radiobiological benefits of a large fraction boost for dose escalation and is a well tolerated treatment option for men with intermediate- to high-risk prostate cancer. Early results are encouraging with biochemical response and acceptable toxicity. These data provide a basis for the design of a phase II clinical trial.
Technology in cancer research & treatment 10/2010; 9(5):453-62. · 2.02 Impact Factor
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ABSTRACT: Prostate cancer remains a medical dilemma and a major cause of morbidity and mortality in many western countries. It represents the most common cancer in US men, with an estimated 192 280 new cases diagnosed in 2009. The median survival for men with metastatic castrate-resistant prostate cancer is 1-2 years, with improvements in survival seen primarily with docetaxel-based therapies. The purpose of this article is to discuss developments of novel agents in the field of metastatic castration-resistant prostate cancer (CRPC), including new cytotoxic agents, immune-based therapies, circulating tumor markers and targeting agents.
During this past year, several promising approaches yielded disappointing results in the phase III setting (GVAX); nonetheless, expectations for other agents (Abiraterone, MDV3100, Zibotentan, immunotherapy agents) still remain high.
Systemic therapy options are limited in CRPC and survival benefit remains to be seen with the new therapies. Circulating tumor cells continue to provide important prognostic information and will likely become an important aspect of future clinical decision-making.
Current opinion in oncology 02/2010; 22(3):263-7. · 4.09 Impact Factor
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ABSTRACT: The standard localized therapies for prostate cancer include external-beam radiation therapy, brachytherapy and radical prostatectomy. There are several novel approaches in development aimed at improving local disease control and survival, and reducing post-treatment complications. In low-to-intermediate-risk patients, new radiation approaches are being explored to include hypofractionated robotic radiation therapy. For high-risk patients, the focus is on multimodality approaches, especially the addition of chemotherapy. Recent developments in radiation therapy and adjuvant chemotherapy are the focus of this review.
Expert Review of Anti-infective Therapy 08/2009; 9(7):953-62. · 2.65 Impact Factor
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ABSTRACT: Prostate cancer continues to represent a major health problem. It represents the most common cancer in US men, with an estimated 186 320 new cases diagnosed in 2008. It is the second leading cause of cancer death in men in the United States. Despite several attempts, the median survival for men with metastatic castrate-resistant prostate cancer is 1-2 years, with improvements in survival seen primarily with docetaxel-based therapies. Treatment options are limited, and there is a clear need for therapies that improve outcome. The purpose of this article is to discuss recent developments in the field of metastatic hormone-refractory prostate cancer, including new cytotoxic agents, antiproliferative agents, immune-based therapies, circulating tumor markers and antiangiogenic agents.
During this last year, several promising approaches yielded disappointing results in the phase III setting (GVAX, satraplatin, DN-101); nonetheless, expectations for other agents (abiraterone, zibotentan, Provenge) still remain high.
These new agents will need to demonstrate survival benefit for approval. Circulating tumor cells have been shown to provide important prognostic information and are anticipated to be incorporated in future clinical decision-making.
Current opinion in oncology 06/2009; 21(3):260-5. · 4.09 Impact Factor
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ABSTRACT: The endothelin-A receptor (ETAR) has been implicated in the progression of prostate cancer.
To investigate the safety and efficacy of the specific ETAR antagonist ZD4054 in patients with metastatic hormone-resistant prostate cancer (HRPC).
Double-blind, placebo-controlled, randomised, parallel-group, multicentre, phase 2 trial in patients attending cancer centres with HRPC and bone metastases who were pain free or mildly symptomatic for pain.
Patients were randomised to receive once-daily oral tablets of ZD4054 10 mg, or ZD4054 15 mg, or placebo.
The primary end point was time to progression, defined as clinical progression, requirement for opiate analgesia, objective progression of soft-tissue metastases, or death in the absence of progression. Secondary end points included overall survival, time to prostate-specific antigen (PSA) progression, and safety. Statistical significance was preset at 20%.
A total of 312 patients were randomised (ZD4054 10 mg, n=107; ZD4054 15 mg, n=98; placebo, n=107). At the primary analysis, median time to progression was 3.6 mo, 4.0 mo, and 3.8 mo in the placebo, ZD4054 10 mg, and ZD4054 15 mg groups, respectively, with no statistically significant difference between ZD4054 groups and placebo (hazard ratio [HR] vs placebo for the ZD4054 10mg group: 0.88 [80% CI: 0.71-1.09]; HR vs placebo for the ZD4054 15 mg group: 0.83 [80% CI: 0.66-1.03]). However, a signal for prolonged overall survival was observed in the ZD4054 treatment groups versus placebo, based on 40 deaths. At a subsequent analysis after 118 deaths, this survival benefit was confirmed (HR vs placebo for the ZD4054 10 mg group, 0.55 [80% CI: 0.41-0.73], p=0.008; HR vs placebo for the ZD4054 15 mg group, 0.65 [80% CI: 0.49-0.86], p=0.052) but the differences in time to progression remained nonsignificant. Median overall survival was 17.3 mo, 24.5 mo, and 23.5 mo in the placebo group, the ZD4054 10 mg group, and the ZD4054 15 mg group, respectively. Discordance between results for time to progression and overall survival may be due to the sensitivity of the definition of progression. Adverse events were in line with the expected pharmacologic effects of an ETAR antagonist.
The primary end point of time to progression was not achieved in this study, but an improvement was seen in overall survival in both active treatment arms. ZD4054 was well tolerated.
Clinicaltrials.gov NCT00090363.
European urology 12/2008; 55(5):1112-23. · 7.67 Impact Factor
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Nancy A Dawson
Cancer 10/2008; 113(9):2376-8. · 4.77 Impact Factor
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ABSTRACT: Docetaxel/estramustine is a known active regimen in hormonerefractory prostate cancer (HRPC). A phase II study was conducted to assess the safety and efficacy of docetaxel/estramustine combined with exisulind, an apoptotic antineoplastic drug.
Eighty men with chemotherapy-naive HRPC were enrolled in a multicenter, cooperative group study. The treatment regimen consisted of oral estramustine (280 mg 3 times daily for 5 days), docetaxel 70 mg/m2, oral exisulind (250 mg twice daily), oral dexamethasone (8 mg twice daily for 3 days), and oral warfarin (2 mg daily).
Seventy-five eligible patients were treated with a median of 6 cycles of therapy. Fortyseven patients (62.7%; 95% CI, 50.7%-73.6%) had a > or = 50% decline in prostate-specific antigen levels. Forty-six patients had measurable disease with 6 partial responses (13%; 95% CI, 4.9%-26.3%). The main grade 3/4 toxicities were neutrophils (79%), fatigue (15%), and thrombosis/embolism (10%). The median time to first progression was 5.1 months (95% CI, 4.4-6.3 months) and the median survival time was 17.8 months (95% CI, 14.7-20.1 months).
The combination of estramustine/docetaxel/exisulind was associated with significant thomboembolic toxicity despite prophylactic warfarin. The contribution of exisulind to toxicity is uncertain. Prostate-specific antigen decline, response rates, and progression-free and overall survival are similar to those reported with docetaxel/estramustine.
Clinical Genitourinary Cancer 10/2008; 6(2):110-6. · 2.61 Impact Factor
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ABSTRACT: Pain from castration-refractory prostate cancer (CRPC) bone metastases is a common event. Although it is assumed that pain represents an adverse prognostic factor, this variable has not been extensively evaluated. The objective of this study was to determine whether men with CRPC who had higher pain interference scores at baseline had worse clinical outcomes compared with men who had lower pain scores.
Data from three randomized phase III multicenter trials conducted by the Cancer and Leukemia Group B from 1992 to 1998 were combined. Eligible patients had progressive CRPC adenocarcinoma of the prostate, an Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate hematologic, renal, and hepatic functions. Seven items from the Brief Pain Inventory were used to assess the impact of pain on a range of daily activities and quality of life, each rated on a scale from 0 to 10.
In 599 men, the median pain interference scores was 17 (interquartile range, 4 to 34), and 38% of the men had opioid analgesic use at baseline. There was a statistically significant association between pain interference scores and risk of death. The median survival times were 17.6 months (95% CI, 16.1 to 19.1 months) and 10.2 months (95% CI, 8.6 to 11.3 months; P < .001) in men with low (< 17) and high (>or= 17) pain scores, respectively. Pain was inversely associated with likelihood of prostate-specific antigen decline, objective response, and time to bone progression.
This analysis demonstrates that pain is a statistically significant predictor of overall survival in men with metastatic CRPC. These results need to be validated prospectively in future phase III trials.
Journal of Clinical Oncology 05/2008; 26(15):2544-9. · 18.37 Impact Factor
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Nancy A Dawson
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ABSTRACT: Classically, advanced prostate cancer has been treated with hormonal therapy and, most recently, chemotherapy. This treatment clearly demonstrated a survival benefit, but never a cure. With the ever-expanding understanding of the pathophysiology of prostate cancer, there has been a recent explosion in the potential molecular targets and novel therapeutic approaches to both advanced and potentially localized prostate cancer. This review will focus on what the author perceives to be the most promising of these new strategies. The endothelin pathway has been identified as pivotal in the viscous cycle of tumorigenesis in bone, leading to the development of endothelial receptor antagonists. Vaccine therapy using autologous granulocyte-macrophage colony-stimulating factor-producing prostate cancer cells has been effective in producing both immune and clinical responses. Randomized clinical trials of the immunotherapy cell product APC8015 (Provenge) have demonstrated improved survival in the hormone-refractory setting. The development of antisense oligonucleotides to segments of mRNA critical to the progression to androgen-independent disease has emerged as one further tool in the expanding armamentarium of potential therapies being tested. Clearly, headway is being made in improving outcomes in this most prevalent health problem.
Expert Review of Anti-infective Therapy 08/2006; 6(7):993-1002. · 2.65 Impact Factor
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ABSTRACT: The epidermal growth factor receptor (EGFR) is overexpressed in 75 to 90% of renal cell carcinomas and may play a role in tumor initiation and progression. Gefitinib (Iressa, ZD1839) is a potent, selective EGFR-tyrosine kinase inhibitor. This trial was undertaken to assess the efficacy and toxicity of gefitinib in advanced renal cell carcinoma.
Oral gefitinib, 500 mg once daily, was given continuously. A single-dose reduction to 250 mg daily was allowed for toxicity. The primary end point was response rate (defined as complete remission + partial remission + stable disease). Secondary end points were progression-free survival, overall survival, toxicity, and correlation of response with EGFR status.
Twenty-one patients were enrolled on this study, and all are evaluable for response and toxicity. Patient characteristics were median age 61 (range, 35-78 years); 17 males, 4 females; median performance status 0 (range 0-2); median number of prior systemic therapies 1 (range, 0-3). The median and mean number of cycles of therapy received was 3 and 4.7 (range, 1-14+). The best response was stable disease in eight patients (38%). Median progression-free survival was 2.7 months. Median overall survival was 8.3 months. The difference in overall survival was significantly different between patients with progressive disease versus stable disease (6.1 months versus 16+ months; Log-Rank test P value < 0.0001). Three patients required a dose reduction, all for grade 3 diarrhea. There was no apparent correlation between EGFR status and stability of disease or progression of disease.
Gefitinib is without significant conventional activity in renal cell carcinoma. The relation of "stable disease" to treatment or to disease-related prognostic heterogeneity remains to be defined.
Clinical Cancer Research 01/2005; 10(23):7812-9. · 7.74 Impact Factor
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ABSTRACT: Androgen deprivation therapy is the cornerstone treatment for men with de novo or recurrent metastatic prostate cancer. Unfortunately, androgen deprivation therapy is primarily palliative, with nearly all men progressing to an androgen-independent state. Hormone-refractory prostate cancer presents significant management challenges and is the focus of this review.
Investigations into the pathophysiology of hormone-refractory prostate cancer, the exploration of chemotherapeutic combinations, novel biological targets, skeletal protectants, and radiopharmaceuticals, as well as new prognostic tools are expanding the clinician's armamentarium and improving patient outcomes.
Bisphosphonates and chemotherapy are providing effective palliative approaches. Phase II trials of taxane-based regimens show higher response rates and longer survival than has typically been achieved with existing standards. Two completed randomized phase III studies to be reported in mid-2004 will more definitively answer the question of whether currently available chemotherapy can improve survival.
Current Opinion in Urology 06/2004; 14(3):185-93. · 2.59 Impact Factor
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ABSTRACT: Antiandrogen withdrawal (AAWD) results in a prostate-specific antigen (PSA) response (decline in PSA level of > or =50%) in 15% to 30% of androgen-independent prostate cancer (AiPCa) patients. Thereafter, adrenal androgen ablation with agents such as ketoconazole (K) is commonly utilized. The therapeutic effect of AAWD alone was compared with simultaneous AAWD and K therapy.
AiPCa patients were randomized to undergo AAWD alone (n=132), or together with K (400 mg orally [p.o.] tid) and hydrocortisone (30 mg p.o. each morning, 10 mg p.o. each evening; n=128). Patients who developed progressive disease after AAWD alone were eligible for deferred treatment with K.
Eleven percent of patients undergoing AAWD alone had a PSA response, compared to 27% of patients who underwent AAWD and simultaneous K (P=.0002). Objective responses were observed in 2% of patients treated with AAWD alone compared to 20% in patients treated with AAWD/K (P=.02). There was no difference in survival. PSA and objective responses were observed in 32% and 7%, respectively, of patients receiving deferred K, and were more common in patients with prior AAWD response. Treatment with K was well tolerated, and resulted in a decline in adrenal androgen levels, which rose at the time of disease progression.
K has modest activity in AiPCa patients, while AAWD alone has minimal activity. Adrenal androgen levels fall with treatment with K and then climb at the time of progression, suggesting that progressive disease while on K may be due to tachyphylaxis to the adrenolytic properties of K.
Journal of Clinical Oncology 04/2004; 22(6):1025-33. · 18.37 Impact Factor
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ABSTRACT: Biochemical-only recurrent prostate cancer presents the ideal setting for assessing novel agents or approaches for prostate cancer treatment. There is no clear evidence that delay in initiation of more definitive androgen-deprivation therapy is harmful, and a simple blood test--the prostate-specific antigen (PSA) level--is readily available to screen for potential antineoplastic activity. Current novel approaches include vaccines, cyclooxygenase-2 (COX-2) inhibitors, selective apoptotic antineoplastic drugs, endothelin-A receptor antagonists, chemotherapy, vitamin D, and peroxisome proliferator-activated receptor-gamma agonists. In this screening process, certain therapies have emerged as delaying PSA progression or decelerating PSA velocity. These therapies, such as the COX-2 inhibitors, will need to proceed to phase 3 trials to answer the more important question of whether this change in PSA dynamics translates into improved survival. Patients enrolling in these trials need to be clearly informed of the limited expectations of these novel exploratory approaches.
Urology 01/2004; 62 Suppl 1:102-18. · 2.43 Impact Factor
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Nancy A Dawson
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ABSTRACT: A multidisciplinary approach to prostate cancer has become the rule and not the exception. Involving the entire team, which includes a medical oncologist, from the time of initial diagnosis is optimal. This facilitates maximal patient education regarding treatment options and enhances informed decision making. A coordinated approach also promotes enrollment on clinical trials, which are often, multimodality, especially in high-risk early stage prostate cancer. Integrated therapeutic strategies throughout the patient's disease course can improve both patient care and satisfaction
The Canadian Journal of Urology 01/2004; 10(6):2036-7. · 0.64 Impact Factor
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Nancy A Dawson
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ABSTRACT: A diversity of bone pathology is present in men with prostate cancer. Androgen deprivation therapy (ADT) can cause significant and progressive osteopoenia and osteoporosis. Bone is also the primary site for metastases leading to associated pain, skeletal fractures and hypercalcaemia. Bisphosphonate therapy decreases bone resorption, which may prevent or reverse loss of bone mineral density. Both pamidronate and zoledronic acid have proven efficacy in preventing ADT-induced bone loss. In a randomised, placebo-controlled trial, in men with hormone-refractory prostate cancer, there was a decreased incidence of skeletal- related adverse events in men receiving zoledronic acid. So far, randomised trials have failed to show improved pain control. Formalised guidelines are needed to help clinicians decide which patients should be treated with bisphosphonates, when to initiate therapy and for what duration.
Expert Opinion on Pharmacotherapy 06/2003; 4(5):705-16. · 3.20 Impact Factor
