Duration Of Pain Response Research Articles

A Prospective Randomised Comparative Study to Evaluate the Effect of Single Dose (6.25Gy Vs 8Gy) Palliative Radiotherapy with Zoledronic Acid in Patients with Painful Bone Metastases

Background: To assess the effectiveness of a single fraction dose of radiotherapy (6.25Gy versus 8 Gy) with zoledronic acid in cancer patients with painful bone metastases in treating pain; quality of life; duration of pain response and incidence of skeletal related events (SREs). Material and methods: A total of 80 patients with bone metastases presented in the department of Radiation Oncology, S.M.S hospital were randomly assigned to: Group A, received single dose of 6.25Gy with Zoledronic acid 4mg and Group B, received single dose of 8Gy with Zoledronic acid 4mg. The main variable was pain which was assessed with 11 point Numeric pain Rating Score (NRS). Results: There were total 80 patients, 40 in each group, with mean age 54.6 years and 54.5 years in group A and B respectively. Most frequent primary malignant sites were lung (36.2%), breast (28.7%), and prostate (8.7%). At 4 weeks post radiotherapy, complete response was 25% in group A, 27.5% in group B and overall response was 82.5% in group A, 85% in group B. At 2 months post radiotherapy complete response was observed in 25% of patients in group A, while 30% in group B and overall response in 85 % in group A and 87.5% in group B. Quality of life improved in both groups. Mean duration of pain relief was 13.5 weeks vs. 14.5 weeks respectively in group A and group B. Conclusion: There was improvement in pain relief and quality of life post radiotherapy in both the groups. On comparison between 2 groups, the overall pain relief was insignificant between the two dose schedules. So a lower dose 6.25Gy is almost as effective as 8 Gy single fractions for treatment of painful bone metastases.

Multi-dimensional evaluation of pain response in low day-age calves to two types of dehorning.

Dehorning calves is necessary to minimize injury because intensive raising circumstances make horned cows more aggressive. However, acute pain is commonly perceived by farm animals when undergoing painful practices such as dehorning, affecting their health status and quality of life. By quantifying the magnitude of pain and discomfort associated with dehorning, we aim to contribute to a more humane and sustainable cattle farming industry. The objective of this study was to evaluate the behavioral, physiological, and emotional effects of acute dehorning pain in calves using two methods: dehorning cream and dehorning hot-iron.30 Holstein calves aged 4 days were selected for the study. These calves were randomly assigned to two experimental groups based on the method of disbudding: dehorning cream (n = 15) and hot-iron dehorning (n = 15). Before and after dehorning, we evaluated their physiological indicators of infrared eye temperature, concentrations of substance P, IL-6, cortisol, haptoglobin, as well as emotional state, and pain-related behavioral reactions. Post-dehorning, the duration of lying down decreased significantly in both groups (DI and DC: 0-4 h) after dehorning (p < 0.05). Both groups exhibited increased frequencies of pain-related behaviors such as head shaking (DI: 1-7 h, DC: 1-6 h), ear flicking (DI: 2-7 h, DC: 2-7 h), head scratching (DI: 2-3 h, DC: 1-7 h), and top scuffing (DI: 2 h, DC: 2-7 h) compared to pre-dehorning (p < 0.05). The DC group demonstrated a higher frequency of head-shaking, ear-flicking, head-scratching, and top-rubbing behaviors, along with a longer duration of lying down (0-4 h), compared to the DI group (p < 0.05). Post-dehorning, play behavior reduced significantly in both groups (6-8 h) (p < 0.05), whereas judgment bias and fear levels showed no significant change (p > 0.05). Physiological measures including eye temperature, and blood levels of substance P and IL-6, did not differ significantly between the groups before and after dehorning (p > 0.05). However, 48 h after dehorning, calves in the DC group had significantly higher haptoglobin levels compared to the DI group (p = 0.015). Additionally, salivary cortisol levels in the DC group increased significantly at 3.5 h and 7 h post-dehorning (p = 0.018, p = 0.043). Both hot-iron and cream dehorning induced pain in calves, as evidenced by increased pain-related behaviors, elevated salivary cortisol, and higher haptoglobin levels, alongside reduced positive behaviors. Notably, these effects were more pronounced in the DC group than in the DI group, suggesting that dehorning hot-iron may be a comparatively less stressful dehorning method for young calves. Moreover, the brief duration of pain response and weaker response to dehorning observed in 13-day-age calves in this study suggests that dehorning at younger ages may be more advisable and warrants further research.

SPIN-01 RADIATION THERAPY ALONE VERSUS RADIATION THERAPY PLUS RADIOFREQUENCY ABLATION/VERTEBRAL AUGMENTATION FOR SPINE METASTASIS: TRIAL IN PROGRESS

BACKGROUNDSpine metastases are a common occurrence in cancer patients and result in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life. METHODS/DESIGNThis is a single-center, prospective, randomized, controlled trial in patients with spine metastases from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum are randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients are treated with EBRT to a dose of 20-30 Gy in 5-10 fractions. The target parameters are measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments. DISCUSSIONThe primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastases, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL. The results from this study will be used to allow for comparisons to alternative treatment approaches. This trial was activated 5/2020 and is open to accrual.

A single arm phase II study of bone-targeted Sn-117\xa0m-DTPA in symptomatic castration-resistant prostate cancer with skeletal metastases

BackgroundSeveral bone-seeking radionuclides have been developed for palliation of metastatic bone pain since 1956, however, so far radium-223 dichloride is the first and only Food and Drug Administration (FDA) approved targeted alpha therapy for metastatic castration-resistant prostate cancer (mCRPC) based on ALSYMPCA phase 3 study. While radium-223 does improve pain and overall survival outcomes, the improvement can come at the expense of side effects such as bone marrow toxicity. The development of new and better treatment with long-standing pain relief is clearly an unmet medical need.MethodsThe study is a non-randomized phase II study. The study population consists of 25 patients with CRPC who had progressed on any lines of prior therapies and whose serum testosterone level is less than 50 ng/dl and have metastatic lesions to at least two bone sites, with at least one site that has clinically meaningful pain at baseline (≥ 4 on an 11-point intensity scale). Eligible patients will be given two cycles of Sn-117 m-DTPA every 8 weeks or 56 days. Treatment will be administered by slow IV injection over 5–10 min. Retreatment after two cycles is allowed if patients meet the following retreatment criteria. The primary objective is to evaluate the efficacy of Sn-117 m-DTPA on sustained pain response in patients with CRPC metastatic to at least two bone sites and at least one with clinically meaningful pain at baseline (≥ 4 on an 11-point pain intensity scale). Sustained pain response is defined as: 1) achieving pain index ≤ 3 within a 12-week period and 2) maintaining pain index ≤ 3 over a 16-week period. The secondary objectives are: safety and tolerability, measurement of Sn-117 m-DTPA activity by gamma-camera dosimetry scans, therapeutic efficacy, time to the first symptomatic skeletal event, duration of pain response, changes in PSA and ALP levels, patient-reported outcomes and progression free survival and overall survival.DiscussionSn-117 m-DTPA is a unique bone-targeting theranostic radiopharmaceutical agent that selectively binds most heavily to bone metastases sites. This study will be the first prospective phase II trial to assess the pain efficacy and anti-tumor activity of Sn-117 m-DTPA in mCRPC with at least one clinically meaningful pain at baseline.Trial registration.ClincialTrials.gov Identifier: NCT04616547.

Radiation therapy alone versus radiation therapy plus radiofrequency ablation/vertebral augmentation for spine metastasis: study protocol for a randomized controlled trial

BackgroundSpine metastasis is a common occurrence in cancer patients and results in pain, neurologic deficits, decline in performance status, disability, inferior quality of life (QOL), and reduction in ability to receive cancer-directed therapies. Conventional external beam radiation therapy (EBRT) is associated with modest rates of pain relief, high rates of disease recurrence, low response rates for those with radioresistant histologies, and limited improvement in neurologic deficits. The addition of radiofrequency ablation/percutaneous vertebral augmentation (RFA/PVA) to index sites together with EBRT may improve pain response rates and corresponding quality of life.Methods/designThis is a single-center, prospective, randomized, controlled trial in patients with spine metastasis from T5-L5, stratified according to tumor type (radioresistant vs. radiosensitive) in which patients in each stratum will be randomized in a 2:1 ratio to either RFA/PVA and EBRT or EBRT alone. All patients will be treated with EBRT to a dose of 20–30 Gy in 5–10 fractions. The target parameters will be measured and recorded at the baseline clinic visit, and daily at home with collection of weekly measurements at 1, 2, and 3 weeks after treatment, and at 3, 6, 12, and 24 months following treatment with imaging and QOL assessments.DiscussionThe primary objective of this randomized trial is to determine whether RFA/PVA in addition to EBRT improves pain control compared to palliative EBRT alone for patients with spine metastasis, defined as complete or partial pain relief (measured using the Numerical Rating Pain Scale [NRPS]) at 3 months. Secondary objectives include determining whether combined modality treatment improves the rapidity of pain response, duration of pain response, patient reported pain impact, health utility, and overall QOL.Trial registrationClinicalTrials.gov NCT04375891. Registered on 5 May 2020.

Effective pain control with very low dose palliative radiotherapy for multiple myeloma patients with painful osseous lesions

Osteolytic lesions are present in 75% of multiple myeloma (MM) patients. Bone pain is a common presenting symptom. Prior case series analyzing palliative radiation (RT) for bone pain in MM patients suggest doses > 12 Gy (EQD2) provide similar excellent palliation. Recent advances in novel biologic agents have significantly improved the overall survival and quality of life for MM patients. We therefore hypothesized that lower-dose palliative RT (LDRT, i.e. EQD2 < 12 Gy) may offer a safe and effective alternative to higher-dose RT (HDRT) for the treatment of bone lesions in MM patients. We retrospectively identified all MM patients treated with RT for painful bone lesions, at either a tertiary care academic center or Veterans Affairs affiliate hospital, between 2013 and 2019. All patients underwent CT simulation and were treated with standard palliative fields. Patients were grouped into the LDRT cohort if the EQD2 < 12 Gy, with all others comprising the HDRT cohort. Patients were routinely seen in follow-up after the completion of RT and assessed for pain response and toxicity per clinic standards. We analyzed the rates of clinical pain response (CPR), differences in acute and late toxicity, duration of pain response, and retreatment rates between LDRT and HDRT groups. Thirty-four patients with 70 treated lesions were included. Twenty-four patients (49 lesions) were treated with HDRT and 10 patients (21 lesions) with LDRT. Median follow up was 16.8 months (IQR = 6.5-42.9 months) among those still alive and 94% of patients went on to receive systemic therapy. Fifty percent of patients in the HDRT cohort had rISS stage 1 MM versus 20% in the LDRT cohort. The median dose of HDRT treatment was 20 Gy (range 8-30 Gy, EQD2 12-32.5 Gy) versus 4 Gy in the LDRT group (range = 4-8 Gy, EQD2 4.67-9.3 Gy). The overall CPR rate was 97%, with CPR for HDRT = 98% and LDRT = 95%. Although acute toxicity appeared greater for the HDRT cohort (24.5%) than the LDRT cohort (9.5%), this was not significant (Χ2 p = 0.15). Five lesions required retreatment, 2 (9.5%) in the LDRT cohort and 3 (6.3%) in the HDRT cohort. Of the LDRT patients, one had progression of a pre-existing pathologic fracture and the other had subsequent CPR upon reirradiation. Pain recurred in 10% of lesions (12% HDRT versus 9.5% LDRT). The median pain response durations were not yet reached and there was no significant difference between the LDRT versus HDRT cohorts (log rank p = 0.91). This analysis suggests that LDRT effectively palliates painful MM bony lesions with acceptable CPR and duration of palliation, despite differences in patient MM stage between groups. LDRT palliation could permit patients to proceed quickly to systemic therapy by minimizing treatment duration and acute side effects. These data support further prospective comparisons of LDRT versus HDRT for palliation of MM bony lesions.

A phase III randomized-controlled, single-blind trial to improve quality of life with stereotactic body radiotherapy for patients with painful bone metastases (ROBOMET)

BackgroundBone metastases represent an important source of morbidity in cancer patients, mostly due to severe pain. Radiotherapy is an established symptomatic treatment for painful bone metastases, however, when conventional techniques are used, the effectiveness is moderate. Stereotactic body radiotherapy (SBRT), delivering very high doses in a limited number of fractions in a highly conformal manner, could potentially be more effective and less toxic.MethodsThis is a phase III, randomized-controlled, single-blind, multicenter study evaluating the response rate of antalgic radiotherapy for painful bone metastases and the acute toxicity associated with this treatment. A total of 126 patients will be randomly assigned to receive either the standard schedule of a single fraction of 8.0 Gy delivered through three-dimensional conformal radiotherapy or a single fraction of 20.0 Gy delivered through SBRT. Primary endpoint is pain response at the treated site at 1 month after radiotherapy. Secondary endpoints are pain flare at 24–48-72 h after radiotherapy, duration of pain response, re-irradiation need, acute toxicity, late toxicity, quality of life and subsequent serious skeletal events. In a supplementary analysis, patient-compliance for a paper-and-pencil questionnaire will be compared with an electronic mode.DiscussionIf a dose-escalated approach within the context of single fraction stereotactic body radiotherapy could improve the pain response to radiotherapy and minimize acute toxicity, this would have an immediate impact on the quality of life for a large number of patients with advanced cancer. Potential disadvantages of this technique include increased pain flare or a higher incidence of radiation-induced fractures.Trial registrationThe Ethics committee of the GZA Hospitals (B099201732915) approved this study on September 4th 2018. Trial registered on Clinicaltrials.gov (NCT03831243) on February 5th 2019.

A Phase 2 Clinical Trial of SABR Followed by Immediate Vertebroplasty for Spine Metastases

To determine the pain response and prevention of vertebral compression fractures (VCFs) after single-fraction stereotactic ablative radiation therapy (SABR) in conjunction with immediate vertebroplasty for spine metastases. Patients with localized spine metastases free from VCF associated with loss of vertebral height with a pain score ≥4 using the visual analog scale were enrolled. Spine SABR was performed with 20Gy delivered to the gross disease and 14Gy to the contiguous bone marrow in a single fraction. Immediate, prophylactic vertebroplasty was performed within 1month after spine SABR. The primary endpoint was pain response at 3months compared to the historical control with external beam radiation therapy from Radiation Therapy Oncology Group study 9714. Secondary endpoints included pain response at 1month, duration of pain response, vertebroplasty rate, VCF rate, local control, and overall survival. Thirty-five patients were enrolled, of whom 29 were deemed eligible and underwent single-fraction spine SABR. Twenty-three of these patients subsequently underwent prophylactic vertebroplasty. The 3-month pain response was significantly improved compared to Radiation Therapy Oncology Group study 9714: 95% versus 51% (P<.0001). The local control with a median follow-up of 9.6months was 92%. The freedom from VCF was 90% at 1year. Spine SABR was well tolerated with no grade 2 or higher toxicities. A single patient with disease extending from the vertebral body into the spinal canal developed vertebroplasty-related myelopathy, which was corrected with surgery. Single-fraction SABR immediately followed by prophylactic vertebroplasty improves pain response compared with conventional radiation therapy while providing long-term pain control and structural stability of the treated spine. Vertebroplasty is well tolerated as a prophylactic measure in patients without loss of vertebral height after spine SABR. Pain response and VCF rates are similar to patients undergoing SABR alone. Thus, patients who would benefit most from the addition of vertebroplasty need to be further identified.

Linear Accelerator-Based Frameless Stereotactic Radiosurgery for Trigeminal Neuralgia with Optical Surface Monitoring: A Community Cancer Center Experience

Trigeminal neuralgia (TN) is classically defined by episodic, severe, shock-like facial pain along the distributions of the trigeminal nerve. Surgical and radiosurgical methods are often considered in patients’ refractory to medical management. Historically, stereotactic radiosurgery (SRS) for TN has been delivered using an SRS system with a bolted headframe. Recent technological advancements have allowed for frameless, linear accelerator-based radiosurgical approaches with equivalent accuracy. To date, published data is lacking regarding the use of frameless SRS in the community setting, as well as the use of continuous optical surface monitoring systems (OSMS) for frameless SRS. In this study, we report on our community cancer center’s experience treating medically refractory TN and other trigeminal neuropathies with a linear accelerator using an OSMS and cone-beam CT (CBCT) for localization. We evaluated the quality and duration of pain response as well as acute and late toxicities. Between 2016 and 2017, patients were treated at our institution for TN refractory to medical management. Baseline information was collected, including age at diagnosis, nerve distribution, duration and severity of pain, other pre-SRS symptoms, and prior interventions. The treatment target was contoured based on fused MRI and head CT obtained in treatment position. A point dose was prescribed to the trigeminal nerve root using a single isocenter. Cranial immobilization was achieved with a stereotactic thermoplastic mask; and setup verification was achieved with an on-board CBCT and OSMS at the time of treatment. Treatment arcs were delivered using a 5mm cone and 6MV FFF photons. Patients were followed at 3 and 6 months post-SRS for evaluation of symptomatic relief and toxicity. A total of 27 patients were treated and reported for follow-up. Median age at symptom onset and treatment was 57.5 and 63 years, respectively. Median typical episodic pain was 5.5 and median maximum pre-treatment pain was 8.5 (out of 10). Patients were treated with SRS in a single fraction with a median of 5 arcs (max 12). One patient unable to obtain a brain MRI received SRS in 5 daily fractions. Median isocenter point dose was 75Gy. At the time of data collection, 22 of 27 patients had at least 1 month of follow-up, with a median follow-up of 7.2 months. Most common acute effects included temporary pain flare (19%) and fatigue (15%). No grade 2+ toxicities were seen. At follow-up, 45% of patients reported being pain free (18% weaned off medications, 27% continuing medications). Another 45% reported improvement in their pain but were not pain free. Only two patients (9%) reported no improvement. Frameless linear accelerator-based SRS with OSMS is a novel modality providing excellent response rates comparable to traditional SRS with low toxicity. Given proper equipment and procedures, this treatment can be safely delivered in a community-based radiation oncology practice.

Procollagen type I N-propeptide is a predictor of skeletal morbidity in patients with malignant osteolytic bone disease on bisphosphonates

There is an urgent need for individualized treatment of malignant bone disease (MBD), as the clinical benefit from bone-targeted therapies is moderate. We assessed the predictive value of the bone formation marker procollagen type I N-propeptide (PINP) for skeletal morbidity in patients with MBD receiving pamidronate. Seventy patients with advanced MBD were randomized to receive pamidronate 60 mg (n = 35) or 90 mg (n = 35) every 3 weeks for six cycles in a double-blind study. PINP was analyzed at baseline and before each administration of pamidronate, using a validated ELISA. Serum PINP concentrations were compared with pain response (visual analog scale VAS, composite pain score) and skeletal morbidity (skeletal-related events, SRE) using Student's T-test, Wilcoxon rank-sum and log-rank test, respectively. Patients with ≥20% pain reduction in the VAS had lower baseline PINP concentrations when compared to patients with <20% VAS response (P < 0.0001). A high baseline serum PINP concentration (highest tertile versus lower two tertiles) was significantly associated with a shorter duration of pain response (P < 0.0001) and a shorter time interval to first SRE (P < 0.008). Sensitivity of a low baseline PINP serum concentration for freedom from SRE at 1 year from randomization was 75% (15 out of 20 patients), while specificity was 82% (27 out of 33 patients). Serum PINP has been shown to be a significant predictor for skeletal morbidity in patients with MBD on pamidronate treatment. Prospective validation of PINP in patients with MBD to assess the prognosis or individualize bone-targeted treatment is justified.

Satraplatin in patients with advanced hormone-refractory prostate cancer (HRPC): Overall survival (OS) results from the phase III satraplatin and prednisone against refractory cancer (SPARC) trial

5003 Background: Satraplatin is a novel oral platinum compound previously reported to reduce risk of disease progression among HRPC pts progressing after prior CT. Herein the impact of satraplatin on OS is reported. Methods: SPARC is a multinational, randomized, double blind, placebo-controlled trial comparing Satraplatin 80 mg/m2/day po x 5 q 5 weeks) + prednisone 5 mg po bid [S] vs placebo + prednisone [P] in patients with metastatic HRPC progressing after prior CT. Progression-free survival (PFS) and OS were co-primary endpoints. Secondary and exploratory endpoints included time to pain progression (TPP), pain response, duration of pain response, objective tumor response, and PSA response. Efficacy analyses were conducted on an intent-to-treat (ITT) basis. Results: 950 pts were randomized 2:1 to S (n=635) and P (n=315). Baseline characteristics were well-balanced across groups. Of all pts, 51% received prior docetaxel and 47% received post-SPARC CT. As reported, S was associated with statistically significant improvements in PFS; TPP; PSA response, objective tumor response, pain response, and duration of pain response. These improvements did not translate into an OS benefit: median OS was 61.3 weeks and 61.4 weeks in the S and P groups respectively (HR = 0.97; 95% CI: 0.83, 1.13). Trends for improved OS was observed in the subgroup of pts who received prior docetaxel (HR = 0.78; 95% CI: 0.61, 0.99; medians 66.1 vs. 62.9) as well as pts who reported a PPI score 2–5 at baseline (HR = 0.88; 95% CI: 0.67, 1.16; medians 45.7 vs. 43.0) when models were adjusted for baseline prognostic factors. In the S group; myelosuppression was the most common toxicity; grade 4 neutropenia was detected in 4% and only one patient experienced grade 4 thrombocytopenia. Grade 3/4 non- hematologic side effects in the S group included infection (4.5%), vomiting (1.6%) and diarrhea (1.9%). Conclusions: Satraplatin is well tolerated and reduces risk of disease progression for men with HRPC progressing after prior CT. Ongoing analyses are planned to define relationships between PFS, pain response, and OS, as well as to elucidate factors (including post-SPARC CT) that may have confounded the ITT survival analysis. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GPC-Biotech GPC-Biotech GPC-Biotech

Current Status and Future Prospects for Satraplatin, an Oral Platinum Analogue

Platinum drugs are major chemotherapeutic agents that are used alone or in combination with other systemic agents and/or radiation therapy in the management of many human malignancies. All three platinum drugs approved by the Food and Drug Administration, cisplatin, carboplatin, and oxaliplatin, are administrated intravenously. Satraplatin is the first orally administered platinum drug under active clinical investigation. Satraplatin and its major metabolite, JM118, have shown antineoplastic activity in in vitro, in vivo, and in clinical settings. Use of satraplatin as an alternative platinum cytotoxic agent is particularly attractive because of the convenience of administration, milder toxicity profile, lack of cross-resistance with cisplatin, theoretical advantage as a radiosensitizer, and activity in cancers historically nonresponsive to platinum drugs. The most mature clinical data for satraplatin come from the recently completed phase III trial that investigated the efficacy of satraplatin and prednisone on hormone-refractory prostate cancer patients who had failed a course of other chemotherapy agents. Preliminary reports show that the combination is statistically superior to placebo and prednisone in multiple end points, including progression-free survival, prostate-specific antigen response, objective tumor response, pain response, and duration of pain response. The difference in overall survival, however, did not reach statistical significance.

Satraplatin (S) demonstrates significant clinical benefits for the treatment of patients with HRPC: Results of a randomized phase III trial

5019 Background: Chemotherapeutic options for HRPC are limited. S is a novel oral platinum compound. Methods: The SPARC trial is a multinational randomized double blind study comparing S 80 mg/m2/day x 5 q5weeks po + prednisone (P) vs placebo + P in HRPC patients (pts) who failed prior chemotherapy. In this analysis, progression-free survival (PFS) was the primary endpoint, defined as a composite endpoint of radiologic progression, symptomatic progression, skeletal events or death. All cases were blindly adjudicated for progression by an independent review committee (IRC). Results: 950 pts were accrued between Sept 2004 and Jan 2006. Baseline characteristics were well balanced between treatment arms. 51% of the pts had received prior docetaxel. 68% were ≥ 65 yrs old and 27% were ≥ 75 yrs old. Pts received a median of 4 courses in the S arm (range:1–28) vs 2 courses in the placebo arm (range 1–16). 802 pts had an IRC defined progression-free (PFS) event consisting in 80% of the cases of radiologic progression, pain progression or death. All analyses were conducted on an intent-to-treat basis. S was associated with a 31% reduction in the risk of PFS events (HR=0.69; 95% CI: 0.60–0.80; p&lt;0.00001) and a 33% reduction in the risk of pain progression (HR=0.67; 95% CI: 0.54 - 0.83; p=0.00028). Consistent results in favor of S were found for PFS and time to pain progression in all subsets examined, including pts treated with prior docetaxel. Superior PSA response (25% vs.12%, p=0.00007), objective tumor response (7% vs. 1%, p&lt;0.002), pain response (24% vs. 14%, p&lt;0.005), and duration of pain response (HR=0.59; 95%CI: 0.35–1.00; p=0.049) were observed for S. Final analysis of overall survival awaits the occurrence of the pre-specified number of events. S was generally well tolerated - myelosuppression was the most frequent side effect, but grade 4 neutropenia was uncommon (4%) and a single patient had grade 4 thrombocytopenia. Grade 3/4 non-hematologic side effects included infection (4%), vomiting (2%) and diarrhea (2%). Conclusions: S is well tolerated and significantly reduces the risk of disease progression for HRPC pts who have failed prior chemotherapy. Supported by GPC Biotech and Pharmion No significant financial relationships to disclose.