Skeletal related events (SREs) in metastatic androgen independent prostate cancer (AIPC) treated with docetaxel-based chemotherapy: Results from ASCENT

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 4614-4614 ◽  
Author(s):  
J. S. Chan ◽  
C. W. Ryan ◽  
P. M. Venner ◽  
D. P. Petrylak ◽  
G. S. Chatta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Cord Compression ◽  
Entire Group ◽  
Large Prospective Study ◽  
Free Survival ◽  
Skeletal Related Events ◽  
The Impact ◽  
Androgen Independent

4614 Background: Docetaxel prolongs survival in AIPC patients and zoledronic acid (ZA) reduces the incidence of SREs. The SRE incidence of patients treated with docetaxel-based chemotherapy has not previously been reported. Methods: ASCENT was a randomized clinical trial that compared weekly DN-101 (calcitriol, 45 μg p.o. on day 1) plus docetaxel (36 mg/m2 iv on day 2 for 3 weeks of a 4-week cycle) to placebo plus docetaxel in patients with chemotherapy-naïve metastatic AIPC. ZA use was not restricted. SRE-free survival was described for the entire group and then compared for patients randomly assigned to DN-101 or placebo and stratified by ZA use. Statistical comparisons were conducted using Cochran-Mantel-Haenszel for incidence and log-rank for SRE-free survival. Results: With a median follow-up of 18.3 months, 33% of subjects experienced at least one SRE and the overall median SRE-free survival was 13 (95% CI 10.5–14.3) months. The incidence of SRE by type was: radiation to bone (18.8%), fracture (10%), spinal cord compression (4%), surgery to bone (0.4%). Eighty-five (34%) patients received ZA. The study was not adequately powered to measure the impact of DN-101 or ZA on SRE endpoints. Exploratory analyses showed a trend for an increase in SRE-free survival (HR 0.78, p = 0.13) of DN-101-treated patients. SRE-free survival and incidence for subgroups were examined ( Table ). Conclusions: This is the first report of SRE incidence in a large, prospective study of docetaxel-based therapy. Improved therapies for reducing SREs in AIPC are needed because the risk of SREs remains high despite the use of modern chemotherapy and ZA. [Table: see text] [Table: see text]

OLI-P: Toxicity and efficacy of local ablative radiotherapy in PSMA-PET staged, oligometastatic prostate cancer—A phase II trial.

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 115-115
Author(s):  
Tobias Hölscher ◽  
Michael Baumann ◽  
Jörg Kotzerke ◽  
Manfred Wirth ◽  
Christian Thomas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Adverse Events ◽  
Hybrid Imaging ◽  
Primary Therapy ◽  
Free Survival ◽  
Psma Pet ◽  
Oligometastatic Prostate Cancer ◽  
Psa Progression

115 Background: After curative primary therapy, a subset of patients with prostate cancer will have PSA-progression. Modern imaging methods may detect patients with oligometastastic disease at an early time point. Local ablative therapy has shown to improve time to progression compared to standard of care. PSMA-PET hybrid imaging is an emerging method, with a high accuracy and sensitivity to detect oligometastatic disease at low PSA-levels. Methods: At two German centers, patients with PSA progression after local curative treatment had PSMA-PET- hybrid imaging. Patients with up to five PSMA-PET positive metastases were offered to participate in the clinical trial. Further relevant exclusion criteria were ongoing androgen deprivation therapy (ADT), PSA >10 ng/ml or severe comorbidity. The patients had a local ablative radiotherapy (aRT) to all PSMA-PET positive metastases. The primary endpoint was toxicity within two years after aRT. Secondary endpoints included PSA-progression free survival (defined as PSA nadir +1 ng/ml or start of ADT) and therapy-free survival (i.e. time to start ADT). Results: Between 2014 and 2018, 72 patients were included; patients’ characteristics are shown in table. Nine patients were excluded as no aRT was performed. The median follow up for the remaining 63 patients was 34.2 months. Within two years, 67 % (42 of 63 pats) had no report of adverse events. Following events were recorded during follow up: rectal bleeding (Grade 1, n=1), stroke (1), urinary incontinence (grade 2: n=3) secondary malignoma (n=5, primary liver tumor (n=2), bladder cancer, acute leukemia and head and cancer). All adverse events were considered as “not related“ to aRT of the metastases. PSA progression occurred in 44 patients after a median of 14.4 months. After two years, PSA relapse free survival was 38.2 %. ADT was initiated in 36 patients after a median of 26 months; 54 % (n=34 of 63) did not start ADT within two years after aRT. Conclusions: Local ablative radiotherapy in selected patients with PSMA-PET staged oligometastatic prostate cancer is well tolerated and may improve midterm outcome and delay onset of systemic therapy. Clinical trial information: NCT02264379. [Table: see text]

Incidence of skeletal-related events (SREs) among prostate cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16035-e16035
Author(s):  
Marianne Ulcickas Yood ◽  
Teresa Maria Zyczynski ◽  
Karen Wells ◽  
Deborah Casso ◽  
Benjamin Gutierrez ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Cancer Patients ◽  
Stage Iv ◽  
Cord Compression ◽  
Population Based ◽  
Tumor Registry ◽  
Ajcc Stage ◽  
Skeletal Related Events

e16035 Background: Skeletal related events (SREs) occur in men with prostate cancer and may result from both bone metastases and exposure to androgen deprivation therapy (ADT). The objective of this study was to quantify the incidence of SREs in patients with prostate cancer treated with ADT or orchiectomy in clinical practice. Methods: Prostate cancer patients served by Henry Ford Health System (HFHS) were identified via the HFHS tumor registry. Eligible patients were newly diagnosed with prostate cancer between 2004 and 2010 and treated with ADT or orchiectomy. Comprehensive population-based data were compiled using tumor registry with linkages to pharmacy, laboratory results, and healthcare encounter databases. SREs included spinal cord compression, surgery to bone, pathologic fracture and radiation to bone. Disease progression and metastases were identified by medical record review. Results: We identified 702 patients with prostate cancer and receipt of ADT or orchiectomy; 57.6% were >70 years of age and 43.7% were African American. 56.3% of patients were initially diagnosed at AJCC stage II, 9.8% at stage III, 22.1% at stage IV, and 11.8% had missing or unknown stage. A total of 93 patients (13.2%) had one or more SREs: radiation to bone (8.5%) and spinal cord compression (3.1%) were the most common SREs. We then limited the cohort to patients initially diagnosed with or progressing to AJCC stage IV prostate cancer (N=207). Among this group, 47.8% were >70 years of age. The mean time from stage IV diagnosis to end of follow-up was 35.6 months. In this subgroup, 16.4% of patients were initially diagnosed at AJCC stage II, 8.2% at stage III, 69.6% at stage IV, and 5.8% had missing or unknown stage. 57 patients (27.5%) had one or more SREs. Conclusions: Some clinical trials have found 36-41% of high-risk metastatic prostate cancer patients developed SREs during 3 years of follow-up. In this population-based cohort of patients with prostate cancer receiving ADT or orchiectomy and treated in real-world clinical practice, we found the incidence of SREs to be lower than what has been reported in clinical trials. Additional analyses exploring the incidence of SREs in patients diagnosed with metastatic castrate resistant prostate cancer will be presented.

Impact of skeletal-related events on survival in patients with prostate cancer metastatic to bones.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 223-223
Author(s):  
Jean A. McDougall ◽  
Bernardo Haddock Lobo Goulart ◽  
Sean D Sullivan ◽  
Jeannine S. McCune ◽  
Aasthaa Bansal ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Metastatic Prostate Cancer ◽  
Pathological Fracture ◽  
Cord Compression ◽  
Time Dependent ◽  
Risk Of Death ◽  
Skeletal Related Events ◽  
The Impact

223 Background: Skeletal related events (SREs), defined as pathological fracture, spinal cord compression, surgery or radiotherapy to the bone, occur in nearly half of men diagnosed with metastatic prostate cancer. Accurate assessment of the risk of death associated with SREs is important to making decisions about the use of recently approved treatments, which have been shown to decrease the frequency of skeletal events, yet estimating the impact of SREs on survival presents several methodological challenges given the recurrent time-dependent nature of exposure. Methods: A cohort of men >65years of age, diagnosed with prostate cancer and bone metastasis between January 1, 2004 and December 31, 2009 was identified from the Surveillance Epidemiology and End Results (SEER) registries were linked to Medicare Parts A and B claims. The outcome of interest, death from any cause, was ascertained from SEER and survival time was calculated from the date of metastatic prostate cancer diagnosis. Multivariable Cox proportional hazards models treating the occurrence of an SRE as a time-dependent exposure were used to estimate the hazard ratios (HR) and corresponding 95% confidence intervals (CI) for the association between SRE occurrence, number, and type, and death. Results: Among 3,297 men with metastatic prostate cancer, 40% experienced ≥1 SRE during the observational follow-up period (median 19 months). Compared to men who remained SRE-free, cohort members who had ≥1 SREs had a two-fold higher risk of death (HR 2.2, 95% CI 2.0-2.4). Those whose first SRE was a pathological fracture had a 2.7-fold higher risk of death (HR 2.7, 95% CI 2.3-3.1), followed by spinal cord compression (HR 2.1, 95% CI 1.8-2.5), surgery (HR 1.8, 95% CI 1.5-2.2) and radiotherapy (HR 2.2, 95% CI 1.9-2.4). Compared to those experiencing only one SRE, men who experienced a second SRE of any type had double the risk of death (HR 2.2, 95% CI 1.9-2.6). Conclusions: SREs were associated with ≥50% reduction in overall survival. This finding is consistent across different types of SREs and supports using therapies to prevent or treat SREs in patients with prostate cancer metastatic to the bones.

BiovaxID™ Vaccine Therapy of Follicular Lymphoma in First Remission: Long-Term Follow-Up of a Phase II Trial and Status of a Controlled, Randomized Phase III Trial.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2441-2441 ◽  
Author(s):  
Carlos Santos ◽  
Lee Stern ◽  
Laura Katz ◽  
Thelma Watson ◽  
Gause Barry
Keyword(s):  
Clinical Trial ◽  
Phase Ii ◽  
Disease Free Survival ◽  
T Cell Response ◽  
Phase Iii ◽  
Patient Specific ◽  
Free Survival ◽  
The Impact ◽  
Disease Free

Abstract Malignant B-cells in Follicular Non-Hodgkin’s Lymphoma expresses a clonal idiotype immunoglobulin which can serve as the basis for a patient-specific anti-idiotype vaccine. In a previous single-arm Phase II study by Bendandi, et al (Nature Med5:1171–1177, 1999), we evaluated the ability of tumor-specific idiotype (Id) conjugated to keyhole limpet hemocyanin (KLH) administered concurrently with granulocyte-monocyte colony-stimulating factor (GM-CSF) adjuvant to induce complete remissions and molecular remissions in treated patients. The vaccine formulation induced a tumor-specific cytotoxic CD8+ and CD4+ T-cell response in patients in first complete remission after standard chemotherapy, as well as achieved molecular remissions in 8 of 11 of these patients. Data available at the time of this abstract for the 20-patient cohort, indicates a median follow-up of 9.167 years. 9 patients (45 %) remain in continuous first CR at their most recent follow-up (either in 2004 or 2005), and overall survival is 95%. The data further indicates the median disease free survival for the cohort is 96.5 months (8.04 years). To date there have been no additional reported mortalities in this cohort. As of August 2005, we report the progress of the Phase III clinical trial for this vaccine, opened in January 2000 by the NCI to evaluate the impact of this hybridoma-based Id vaccine on disease-free survival in a group of up to 375 previously untreated patients who have attained a CR or CRu from PACE [Prednisone, Doxorubicin, Cyclophosphamide, and Etoposide (ProMACE without methotrexate)] chemotherapy, and who are randomized to receive either vaccine or control. To date, 187 patients have been accrued onto the study. Of those patients, 145 (77.5%) achieved a CR or Cru and are being followed in this ongoing clinical trial.

Denosumab for the prevention of symptomatic skeletal events in patients with castration-resistant advanced prostate cancer: A comparison with skeletal-related events.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 35-35 ◽  
Author(s):  
Matthew R. Smith ◽  
Robert E. Coleman ◽  
Laurence Klotz ◽  
Kenneth B. Pittman ◽  
Piotr Milecki ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Spinal Cord ◽  
Spinal Cord Compression ◽  
Controlled Trial ◽  
Cord Compression ◽  
Castration Resistant ◽  
Pathologic Fractures ◽  
Skeletal Related Events ◽  
Fracture Surgery

35 Background: In a randomized controlled trial of men with castration-resistant prostate cancer (CRPC) and bone metastases, denosumab was superior to zoledronic acid (ZA) for reducing skeletal-related events (SRE, defined as pathological fracture, surgery or radiation to bone [including the use of radioisotopes], or spinal cord compression) (Fizazi, et al. Lancet 2011;377:813-822.). Recently, the composite endpoint of symptomatic skeletal event (SSE, defined as symptomatic fracture, surgery or radiation to bone, or spinal cord compression) was introduced as an alternative term/clinical trial endpoint to describe skeletal morbidity. Methods: Men with CRPC, ≥ 1 bone metastasis, and no prior IV bisphosphonate use received either SC denosumab 120 mg or IV ZA 4 mg (adjusted for creatinine clearance) in a blinded fashion every 4 weeks. Oral calcium and vitamin D supplements were recommended. SSEs included pathologic fractures considered symptomatic by the investigator, spinal cord compression and surgery and radiation to bone. Results: As previously reported, fewer men who received denosumab than ZA had confirmed first SREs, and experienced multiple SREs (Table). Similarly, fewer patients in the denosumab group than the ZA group had confirmed first SSE and multiple SSEs. The median (95% CI) estimate of time to first SSE (superiority analysis) for denosumab was not reached (28.8 mo, not estimable), and for ZA it was 24.2 (20.7, 30.2) mo (HR = 0.78 (0.66, 0.93) P = 0.01). Conclusions: Denosumab reduced the risk of skeletal events in men with CRPC regardless of endpoint definition as SRE or SSE. The risk of developing SSEs was reduced by up to 22% when comparing denosumab with ZA. Clinical trial information: NCT00321620. [Table: see text]

Outcome for metastatic (M+) medulloblastoma (MB) treated with carboplatin during craniospinal radiotherapy (CSRT) followed by cyclophosphamide (CPM) and vincristine (VCR): Preliminary results of COG 99701

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 2017-2017 ◽  
Author(s):  
R. Jakacki ◽  
P. Burger ◽  
T. Zhou ◽  
E. Holmes ◽  
R. Packer ◽  
...  
Keyword(s):  
Entire Group ◽  
Free Survival ◽  
Promising Strategy ◽  
Surgical Debulking ◽  
Central Pathology ◽  
The Impact ◽  
Negative Predictor ◽  
Pathology Review ◽  
Carboplatin Dose

2017 Background: The outcome for patients with metastatic medulloblastoma has historically been poor. Carboplatin is both a potent radiosensitizer and has activity against medulloblastoma. In this study, we evaluated the feasibility of administering carboplatin during CSRT and the impact of anaplasia as an independent predictor of outcome. Methods: All patients underwent surgical debulking followed by 36 Gy CSRT with boosts to the posterior fossa and sites of bulk disease. During CSRT, patients received weekly VCR as well as carboplatin doses ranging from 30 mg/m2/dose x 15 to 45 mg/m2/dose x 30 given 1–4 hours prior to each RT fraction, using a Phase I design. G-CSF was given for neutropenia during CSRT. Six weeks after completing chemoradiotherapy, patients received six courses of monthly CPM (2 gm/m2) and VCR. Central pathology review was performed to confirm the diagnosis and assess for anaplasia. Results: 57 patients (median age 7.3 yrs, range 3.1–18.1 years, M/F ratio of 2.6:1) with centrally reviewed M+ MB were enrolled. Thrombocytopenia was dose limiting and 35 mg/m2/dose x 30 was selected as the maximum tolerated carboplatin dose. 20 patients (35%) had severe anaplasia. There was no difference in age, M/F ratio or distribution of M-stage between those with or without anaplasia. Median follow-up for surviving patients is 4.5 yrs. Four-year overall survival (OS) and event-free survival (EFS) for the entire group is 81 ± 5% and 66 ± 6%. Four-year OS is 89 ± 5% for patients without anaplasia vs. 65 ± 11% for those with anaplasia (log-rank p=0.002). Four-year EFS is 76 ± 7% for patients without anaplasia vs. 48 ± 12% for those with anaplasia (log-rank p=0.02). There was no difference in survival based on M-stage. Conclusions: The use of daily carboplatin as a radiosensitizer appears to be a promising strategy for patients with metastatic MB. The presence of anaplasia is a significant negative predictor of outcome. No significant financial relationships to disclose.

The impact of neoadjuvant weekly ixabepilone for high-risk prostate cancer: A phase I/II clinical trial.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 158-158 ◽  
Author(s):  
Jodi Lyn Layton ◽  
Angela Marie Plette ◽  
Joseph F. Renzulli ◽  
E. Bradley Miller ◽  
Howard Safran ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
High Risk ◽  
Phase I ◽  
High Risk Prostate Cancer ◽  
Post Surgery ◽  
Risk Prostate Cancer ◽  
Psa Response ◽  
The Impact

158 Background: Potential benefits of neoadjuvant chemotherapy are tumor downstaging and treatment of micrometastatic disease. A prior study using docetaxel yielded no pathologic complete responses and concerns for increased operative morbidity. In Phase II studies, ixabepilone has promising activity in metastatic prostate cancer. Our study is a Phase I/II clinical trial evaluating neoadjuvant, weekly ixabepilone in men with high-risk prostate cancer opting for radical prostatectomy. Methods: Men with high risk prostate cancer defined as either Gleason 8-10, cT3 disease, high volume Gleason 4+3 and a palpable nodule or a PSA>20 ng/ml were eligible. Men received weekly ixabepilone 16-20/m2 for 12-16 weeks prior to surgery. Fifteen men underwent robotic prostatectomy; one patient who had an open prostatectomy. Initial PSA response, post-operative PSA values, pathology, and evaluation of adverse events were recorded. Results: We enrolled 16 men with a mean follow-up of 15.25 months at time of review. All had pretreatment Gleason scores of 4+3 or higher. With neoadjuvant treatment, PSA values decreased in 14/16 men (mean 46.8%); increased in 2/16 men. None reached an undetectable pre-operative PSA. Nine men experienced an adverse event requiring dose modification or cessation of chemotherapy (neuropathy or allergic reaction). Only 5/16 men completed planned treatment. Mean operative time, EBL, and hospital stay were 189 minutes, 184mL, and1.5 days, respectively; all consistent with institutional and national norms. Post surgery 15/16 (94%) had pT3 disease, 8/16 (50%) had a positive surgical margin and 2/16 (12.5%) had positive regional lymph nodes. There were no pathologic complete responses. Only 1/16 (6.25%) had a biochemical relapse. Conclusions: While a PSA response is achieved, there is substantial toxicity with neoadjuvant weekly ixabepilone. Men were able to undergo prostatectomy without increased morbidity after neoadjuvant therapy. Extracapsular extension and positive surgical margins remained common in this population with high-risk disease. Assessment of biochemical recurrence rates and time to treatment failure will require longer, planned follow-up.

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