bluuebunny/crossref_metadata_2025_split huggingface dataset:
Quality of life (QOL) of patients (pts) with metastatic hormone refractory prostate cancer (mHRPC) following treatment with docetaxel or mitoxantrone in the TAX-327 study
Authors: Pond G. R. , Berthold D. R. , Dewit R. , Eisenberger M. , Tannock I. F. 
Published: March 2020

4557 Background: The TAX-327 study compared 3-weekly docetaxel (D3), weekly docetaxel (D1) or mitoxantrone (M), each with prednisone (P) for 1006 pts with mHRPC. Survival and symptom control were superior for treatment with D3+P as compared to M+P (Tannock et al, NEJM 2004;351;1502–12). Here we investigate QOL and its relation to pain, and effects of treatment on QOL in pts with minimal symptoms. Methods: Pts were assessable for pain response if Present Pain Intensity (PPI) ≥ 2 (range 0–5) or Analgesic Score (AS) ≥ 10. QOL was measured by the FACT-Prostate (FACT-P) self-report score (range 0–156, higher scores indicate better QOL). QOL response required a 16-point increase in FACT-P score maintained on 2 occasions; here deterioration of QOL was defined by a 16-point decrease from baseline in FACT-P score. Pts with minimal symptoms were defined at baseline by a FACT-P score > 128 or by PPI < 2 and AS < 10. Results: QOL was substantially impaired at baseline (FACT-P score ≤128) in 92% and 75% of pts who were and were not assessable for pain (p < 0.001). Correlation of FACT-P score with PPI and AS will be presented. QOL response and deterioration for all assessable pts, and for those with minimal symptoms are shown in the table (p-values compared with M+P). Time-dependent analysis of QOL and its relation to duration of treatment will be presented at the meeting. Conclusions: Most pts had impaired QOL at baseline regardless of pain. There was greater improvement in QOL following treatment with D+P compared to M+P for all pts and for pts with minimal symptoms. With the caveat that unequal withdrawal of pts might bias the data, there was greater probability of decline in QOL for pts receiving weekly docetaxel. [Table: see text] [Table: see text]
Phase II study of low dose (LD) and high dose (HD) premarin in androgen independent prostate cancer (AIPC)
Authors: Pomerantz M. , Manola J. , Taplin M. , Bubley G. , Inman M. , Lowell J. , Kantoff P. , Oh W. K. 
Published: March 2020

4560 Background: Estrogens, including DES, transdermal estradiol, estramustine and PC-SPES, have shown antitumor activity in AIPC. We tested two doses of Premarin to determine efficacy and safety of this commonly available estrogen. Methods: Patients with progressive AIPC were eligible. Prior estrogen use, significant cardiac or thromboembolic disease, and concurrent steroids were not allowed. Patients were randomized to Premarin 1.25 mg once (LD) or 3 times (HD) daily. Prophylactic breast irradiation was encouraged and warfarin 1 mg daily was required, unless contraindicated. After the first stage of accrual, the LD arm was closed because of limited activity, while the HD arm continued to the 2nd stage. Results: 46 patients were enrolled; 17 patients were randomized to LD Premarin, 29 patients assigned to HD Premarin by randomization or direct assignment. One patient withdrew consent prior to therapy. Median follow up is 5.3 months. Median age was 69 years (range 52–86) and median PSA 84.6 ng/ml (range 2.5–794.1). 19 patients (41%) had measurable disease. PSA declines ≥ 50% were seen in 0% (95% C.I., 0–19.5) and 32.1% (95% C.I., 15.9–52.4) of patients treated with LD and HD premarin. 1 patient treated with HD Premarin had a partial measurable response (8.3%; 95% C.I., 0.2–38.5). Median time to progression was 3.3 and 3.2 months in the LD and HD arms, respectively. Premarin was well tolerated in 45 evaluable patients. One grade 4 toxicity was noted, a stroke in the LD arm. Grade 3 toxicity was rare with 1 allergic reaction, 2 DVTs and 3 episodes of GI toxicity in one patient. Two patients experienced grade 3 elevations in PT requiring modification of warfarin dose. No significant gynecomastia was reported. Analysis of serially drawn hormone levels and molecular correlates of treatment response is pending. Conclusions: HD Premarin is associated with a 32.1% PSA response rate, while no responses were seen with LD Premarin. A measurable response was noted in 1 of 12 patients treated with HD Premarin. Toxicity was modest, though thromboembolism was seen even with prophylactic warfarin. Ongoing studies are evaluating molecular and clinical predictors of response. No significant financial relationships to disclose.
Salvage chemotherapy with paclitaxel, ifosfamide, and nedaplatin in patients with urothelial cancer who had received prior cisplatin-based therapy
Authors: Shinohara N. , Harabayashi T. , Suzuki S. , Nagao K. , Nagamori S. , Matsuyama H. , Naito K. , Nonomura K. 
Published: March 2020

4579 Background: The combination chemotherapy of paclitaxel, ifosfamide, and nedaplatin (PIN regimen) has been shown to be effective in patients with advanced urothelial cancer. The aim of this presentation is to evaluate long-term followup outcomes in patients who had treated with standard cisplatin-based chemotherapy. Methods: The PIN regimen consisted of paclitaxel 175 mg/m2 on day 1, ifosfamide 4.5 g/m2 divided over days 1, 2 and 3, and nedaplatin 70 mg/m2 on day 1; PIN was given every 28 days. The doses of nedaplatin and ifosfamide were reduced according to the impairment of renal function (24h CCr) just before starting each cycle of PIN therapy Results: Thirty two patients who had previously undergone cisplatin-based chemotherapy were entered onto the study (median age, 66 years; median performance status, 1, median 24h CCr, 62ml/min [29–119ml/min] ). Metastatic sites at study entry included the lymph nodes (24), lung (6), bone (5), primary (5), soft tissue (3), and liver (2). Among the 32 assessable patients, there were 5 CRs (16%) and 19 PRs (59%) for an overall RR of 75 % (95% confidence interval [CI], 59–91 %). The median time to progression was 8 months (range, 0–50+ months) and the median survival was 22 months (range, 4–52+ months). Twelve patients received the full dose of PIN combination (median 5 cycles) and 20 patients required dose reduction (median 3 cycles). Nine of 12 (75%) patients who were treated with the full-dose PIN combination obtained a CR or PR, as did 15 of 20 (75%) patients who required dose reduction. Grades 3 and 4 neutropenia occurred in all patients. Febrile neutropenia occurred in 8 (25%) patients. Grades 3 and 4 thrombocytopenia occurred in 8 (25%) patients. Grades 3 and 4 anemia was observed in 6 (19%) patients. Grade 3 neuropathy occurred in 1 (3%) patient, who could not continue to receive additional cycles of PIN combination after 3 cycles. No patient experienced renal failure. There were no treatment-related deaths. Conclusions: The PIN combination was highly active and tolerable in patients who had previously treated with cisplatin-based chemotherapy, and might be suitable for those with mild to moderate renal insufficiency. No significant financial relationships to disclose.
Thyroid function tests (TFTs) abnormalities in patients (pts) with metastatic renal cell carcinoma (mRCC) treated with sunitinib
Authors: Shaheen P. E. , Tamaskar I. R. , Salas R. N. , Rini B. I. , Garcia J. , Wood L. , Dreicer R. , Bukowski R. M. 
Published: March 2020

4605 Background: Sunitinib is a multi-targeted receptor tyrosine kinase inhibitor of vascular endothelial growth factor and platelet-derived growth factor receptors. It has anti-tumor activity in mRCC pts with toxicity including fatigue. We investigated TFTs abnormalities and related signs and symptoms in pts with mRCC receiving sunitinib. Methods: The medical records of pts with mRCC enrolled in 4 ongoing clinical trials of sunitinib were reviewed. TFTs assessment (TSH, T3 and T4) was undertaken based on the clinical suspicion of treating physicians. Patient demographics, frequency and values of TFTs and any signs and symptoms of thyroid dysfunction were collected. Abnormal TFTs and treatment outcome were correlated. Results: Between 5/2004 and 12/2005, 62 pts (43 males, 19 females) were treated with sunitinib. The median age was 58 years (range, 23–72). Fifty-five pts had TFTs assessed while on treatment and 40 pts (65% of total) had one or more abnormality. Two pts had well-controlled hypothyroidism prior to initiation of sunitinib. TFTs abnormalities were consistent with hypothyroidism in all pts including one who initially developed transient hyperthyroidism. Signs and symptoms possibly related to hypothyroidism were found in 33 pts (53% of total) with abnormal TFTs and were initially attributed to sunitinib. Signs and symptoms included fatigue in 33 pts, anorexia in 20 pts, fluid retention in 17 pts, and skin/hair changes in 13 pts. Thyroid hormone replacement was undertaken in 12 pts and resulted in improvement of symptoms in 6 pts. Among the 40 pts with abnormal TFTs 29 pts had tumor evaluation; 13 had SD, 8 had PR, 2 had CR. There was no correlation between abnormal TFTs and treatment outcome. Conclusions: TFTs abnormalities are common in pts with mRCC treated with sunitinib. Thyroid hormone replacement is indicated in such pts to improve hypothyroidism-related symptoms and possibly to improve treatment tolerance. [Table: see text]
Is physical function affected by androgen deprivation therapy (ADT) in men with non-metastatic prostate cancer?
Authors: Gogov S. , Hussain F. , Naglie G. , Tannock I. , Fleshner N. E. , Krahn M. D. , Duff Canning S. , Warde P. , Alibhai S. M. 
Published: March 2020

4615 Background: Although prolonged use ofADT is hypothesized to adversely affect physical function, only a few small studies have examined this relationship and it remains unclear if self-reported weakness represents a decline in actual physical performance or is related to fatigue. Loss of physical function may be particularly important to older men who already have limited functional reserves. Methods: Men age 50 or older with non-metastatic prostate cancer who were starting continuous ADT were enrolled in this prospective longitudinal study. Physical function was tested using a Jamar dynamometer (grip strength), the Timed Up and Go (TUG) test, and the six-minute walk test (6MWT), representing upper extremity strength, lower extremity strength, and endurance, respectively. Assessments were done at baseline (prior to ADT), 3 months, 6 months, and 12 months. Results: 42 patients on ADT have been enrolled to date (mean age 74.8 y). There was a gradual but steady decline in grip strength from baseline (39.2 kg) to 3 months (38.1 kg), 6 months (37.9 kg), and 12 months (35.3 kg) (p < 0.05 for all comparisons). On average, patients took 7.3 seconds to complete the TUG and walked 1507 feet during the 6MWT at baseline. TUG and 6MWT scores did not worsen over time (p > 0.05). Conclusions: Preliminary data suggest that 3–12 months of ADT is associated with worsening upper extremity strength but lower extremity strength and endurance are relatively unaffected. A larger sample size is needed to determine if all aspects of physical function or only upper extremity strength deteriorate with ADT use. Additionally, most patients in our study reported excellent health and functional status at baseline and our results may not adequately reflect the impact of ADT in more frail older men. No significant financial relationships to disclose.
Prostate specific antigen doubling time (PSA-DT) and velocity (PSA-V) provide independent prognostic information in androgen independent prostate cancer (AIPC) patients receiving chemotherapy
Authors: Daskivich T. J. , Regan M. M. , Kantoff P. W. , Oh W. K. 
Published: March 2020

4616 Background: PSA-DT and PSA-V at AIPC have each demonstrated prognostic significance in retrospective studies. No study has compared PSA-DT and PSA-V at AIPC to determine if they are independent prognostic factors. Methods: PSA-DT and PSA-V were calculated in 91 AIPC patients treated with taxane chemotherapy. PSA-DT was calculated as log 2 divided by the slope of the linear regression of log PSA versus time, from the first rise above the PSA nadir on androgen deprivation therapy (ADT) until the start of the next treatment. PSA-V was calculated from the slope of the linear regression of the raw PSA values over time. PSA-DT and PSA-V were split into tertiles for analysis. The primary endpoint was overall survival (OS) from the date of AIPC. OS was analyzed using Cox proportional hazards regression. Results: In univariate analysis, shorter PSA-DT and higher PSA-V were associated with decreased OS. Also associated with decreased OS were: higher M stage at dx; PSA nadir on ADT >0.2; <12 wks to failure of ADT; presence of mets, bony mets, low Hb, high AP, and low albumin at AIPC; and type of chemotherapy. In multivariate analysis, PSA-DT ≤12 weeks (HR=3.2), PSA-V >10 ng/ml/yr (HR=2.8), PSA nadir >0.2 on ADT, low Hb, and type of taxane chemotherapy persisted as significant predictors of decreased OS (each p < 0.01). Rapid PSA-DT (≤12 wks) and high PSA-V (>10 ng/ml/yr) predicted the worst prognosis (25 mos median OS, unadjusted); slow PSA-DT (>12 wks) and low PSA-V (≤10 ng/ml/yr) the best prognosis (75 mos); and other combinations had intermediate prognoses (49 and 50 mos). Modifications of PSA-DT calculation such as nadir subtraction did not alter prognostic ability of either component. Conclusions: PSA-V at the start of AIPC contributes prognostic information independent of PSA-DT. Future studies should investigate the relative contribution of each of these factors in predicting survival. No significant financial relationships to disclose.
A phase II study of a weekly schedule of BMS-247550 for patients with hormone-refractory prostate cancer: A trial of the Eastern Cooperative Oncology Group (E3803)
Authors: Liu G. , Wang W. , Dipaola R. , Carducci M. , Wilding G. 
Published: March 2020

4618 Background: BMS-247550 (ixabepilone) is an epothilone B analogue with activity in taxane-resistent cancer cell lines. Ixabepilone has been administered using a q3wks schedule with significant neutropenia observed. Here we assess the activity and toxicity of ixabepilone, administered using a weekly schedule, in men with metastatic hormone-refractory prostate cancer. Methods: Patients with metastatic hormone-refractory prostate cancer (chemonaive and prior taxane) were treated with ixabepilone at 20 mg/m2 IV weekly × 3, in 4 wk cycles. This non-comparative study had a planned accrual of 29 chemonaive and 27 prior-taxane treated patients in order to detect a 50% PSA reduction using Consensus Criteria in at least 50% (91% power, α = 0.10) chemonaive and 30% (power 90%, α = 0.10) prior-taxane treated patients. Results: 32 pts with chemonaive and 37 pts with prior-taxane have been enrolled on this study. Median follow-up is 1.8 and 4.1 months respectively. Safety data is reported for the first 56 subjects (24 chemonaive and 32 prior taxane). Hematologic toxicity: Grade 3/4 neutropenia was seen in 10 pts (5 chemonaive, 5 prior-taxane). No significant thrombocytopenia was observed. Grade 3/4 neuropathy was seen in 7 pts (2 chemonaive, 5 prior-taxane). Grade 3 fatigue noted in 8 (3 chemonaive, 5 prior-taxane), grade 3 diarrhea in 5 (4 chemonaive, 1 prior-taxane), and grade 3 nausea in 3 subjects. Lastly, 2 subjects were reported to have developed a grade 3 ileus during therapy. Conclusions: In 56 subjects, BMS-247550 was found to have an acceptable toxicity profile when administered using a weekly schedule. Myelosuppression appeared to be improved, as compared to historical data with the q3wk schedule, using this dose and schedule. PSA/objective responses have been seen but at this time, no conclusion regarding its activity in the first or second-line setting can be made, as the response assessment is ongoing. Complete toxicity and response data will be presented for the entire group. No significant financial relationships to disclose.
Pre-treatment PSA velocity (PSAV) is not predictive of outcomes after radical prostatectomy (RP) in a referral cohort
Authors: Hung A. , Depaula L. P. , Mongoue-Tchokote S. , Garzotto M. 
Published: March 2020

4619 Background: PSA velocity has recently been reported as a significant predictor of prostate cancer-specific mortality in early-staged cancer patients selected from a large screening trial where the median PSA was 4.3ng/ml. In order to determine the broad applicability of these data to a more general population, we examined the effect of PSAV in a referral cohort. Methods: We analyzed over 643 prostate cancer cases diagnosed from 1995–2005. 196 patients underwent RP as definitive therapy. One patient received neoadjuvant hormonal therapy and was excluded. Our goal was to identify whether PSAV prior to RP was predictive of Relapse-Free Survival (RFS) and Overall Survival (OS). 156 patients had at least 2 pre-op PSA values available for the calculation of PSAV (median = 3 values/patient). PSAV was calculated by linear regression analysis using all pre-treatment PSA values available. Results: With a median f/u of 54 months, there were 14 deaths and 26 patients had biochemical relapse. At 5 years, OS was 93% and RFS was 91%. Surprisingly, no patients with biochemical relapse have died, and thus prostate cancer-specific mortality is 0%. In addition to the variables in the table below, seminal vesicle involvement (p = 0.015) and margin positivity (p=0.005) were also significantly associated with RFS confirming the expected prognostic factors in our cohort. On multivariate analysis, Gleason Grade was the only significant predictor of overall survival. For RFS, Gleason Grade, margin involvement, and pre-treatment PSAs were the only significant variables. Neither PSAV nor PSA Doubling Time were significantly associated with RFS or OS by univariate or multivariate analysis. Conclusions: Pre-treatment PSAV is not significantly associated with prostate cancer outcomes in a heterogenous population referred for an elevated PSA. Gleason Grade is still the most significant predictor of overall survival. [Table: see text] No significant financial relationships to disclose.
Five year follow up of a phase II study of cytotoxic immunotherapy combined with radiation in newly diagnosed prostate cancer
Authors: Aguilar L. K. , Teh B. , Mai W. , Caillouet J. , Ayala G. , Aguilar-Cordova E. , Butler E. 
Published: March 2020

4635 Background: In the U.S. there are about 70,000 annual prostate cancer recurrences. The purpose of this study is to evaluate a product to decrease incidence of recurrence. This study is based on objective clinical responses in Phase I studies with AdV-tk (ProstAtak™, Advantagene, Inc) as monotherapy in recurrent disease and preclinical data demonstrating synergy between AdV-tk and radiation. AdV-tk is an adenoviral vector expressing the herpes thymidine kinase gene delivered to the prostate via TRUS-guided injection followed by 14 days of oral prodrug. The mechanisms of function involve direct tumor cytotoxicity, local elicitation of danger signals, recruitment and activation of antigen presenting cells and stimulation of systemic anti-tumor T-cell immunity. Method: AdV-tk was evaluated in combination with radiation in 66 newly diagnosed patients: 33 low risk (Arm A, PSA <10, Gleason <7, and T1c-T2a) and 33 intermediate-high risk (Arm B, PSA ≥10, Gleason ≥7, or T2b-T3). Arm A received two treatments with AdV-tk, immediately before and 14 days into radiation. Arm B received an additional treatment at initiation of androgen deprivation therapy. Results: Two surrogate and one definitive end-point were evaluated. Frequency of patients in Arm A with PSA nadir ≤0.2 ng/ml was 71% vs 56% in a control group of concurrent patients without AdV-tk. The two-year pathologic complete response (pCR) rate by sextant biopsy was 90% in Arm A and 94% in Arm B, compared to an expected range of 70–73%. Freedom from failure (FFF) after 60 month median follow up is 100% for Arm A and 90% for Arm B (95% for intermediate, 75% for high risk) vs best reported results of 79–90% for low risk and 48–79% for intermediate-high risk patients. The three failures in Arm B occurred within months after treatment leading to a Kaplan-Meier curve that plateaus at 90% beyond year 3. This is notably different than previous reports in which the curves continue to drop beyond year 5. Conclusion: These results suggest that AdV-tk combined with radiation therapy may significantly reduce the recurrence rate in patients with prostate cancer, particularly in patients with intermediate-high risk disease. A randomized controlled trial is warranted. [Table: see text]
Gene profiling in transurethral resection samples of patients with hormone-refractory prostate cancer (HRPC)
Authors: Stoss O. , Albers P. , Werther M. , Zielinsky D. , Jost N. , Rueschoff J. , Henkel T. 
Published: March 2020

4641 Background: Patients with metastatic carcinoma of the prostate (CaP) develop after a mean of 15 months resistance to hormone ablation therapy. However, the underlying molecular mechanisms are still unknown. Our goal was to identify the transcriptional changes that are characteristic for the transition to hormone resistant prostate cancer (HRPC) using oligonucleotide microarrays. Here, we report the attempt to profile fresh frozen tissue obtained by palliative transurethral resection (TUR) in patients with HRPC and concomittant urinary obstruction. Methods: Indications for palliative TUR were locally progressive tumors with obstruction and voiding problems. HRPC was defined according to the criteria of Scher et al. 1995. Samples of 8 HRPC patients were compared to tissues from 8 hormone-sensitive CaP patients including biological and technical replicates. All tissue samples had been pathologically evaluated. Only macrodissected prostate samples with at least 70% tumor content were used for RNA extraction. RNA quality was controlled using the Bioanalyzer Nanochip (Agilent Technologies, Palo Alto). Expression analysis was performed on Affymetrix oligonucleotide arrays. Results: We identified 323 genes being significantly deregulated (corrected p-value <0.05, false discovery rate <0.05). These genes were mapped to cellular pathways using the KEGG annotation and the most significantly deregulated pathways were identified. Deregulation of metabolic pathways included fatty acid metabolism as well as oxidative phosphorylation and ATP synthesis. Cell cycle control seems to be further suppressed by the downregulation of JNK-pathway via MEKK4 and JUND, the downregulation of p21 (CDKN1A) and the induction of Cylcin D1. We also present evidence for a significant downregulation of actin cyctoskeleton components. Deregulated genes likely to be specific for the transition from prostate carcinoma to HRPC will be presented. Conclusions: Gene expression profiling has been successfully standardised using fresh TUR material of HRPC patients. Deregulated genes have been mapped to specific signal transduction pathways. On this platform, clinical trials in patients with HRPC using specific inhibitors of cell signalling are being developed. [Table: see text]