bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapamycin for androgen-independent prostrate cancer (AIPC)
Authors: Sharef S. , Jac J. , Khan M. , Amato R. J. 
Published: March 2020

14584 Background: Genetic alterations targeting the PTEN tumor-suppressive gene are among the most frequently noted mutations in human cancers. Prostate cancer has been reported as a PTEN-null cancer. Absence of functional PTEN in cancer cells leads to activation of downstream components of the P13K pathway, including the Akt and mTOR kinases. Drug targeting of these kinases might have significant therapeutic activity in PTEN-null cancers. Rapamycin has been reported to inhibit metastatic prostate tumor growth and angiogenesis in in vivo mouse models. This clinical trial is designed to assess the anti-tumor activity, toxicity and the clinical relationship between tissue and plasma levels of vascular endothelial growth factor and tissue microarray for PTEN tumor-suppressive gene. Methods: Eligibility included: a minimum of 2 consecutive rises in prostate-specific antigen (PSA), with or without radiographic evidence of disease, castrate levels of serum testosterone (≤ 50 ug/l), anti-androgen withdrawal, no more than 2 prior therapeutic regimens, Zubrod performance status of ≤ 2 and adequate organ/marrow function. The initial dose of Rapamycin is 0.15 mg/kg followed by 0.04 mg/kg daily without interruption. Rapamycin levels are obtained every 28 days with a dose adjustment of 0.04 to 0.06 mg/kg in order to maintain a level between 6–10 ng/ml. Results: To date, 12 patients (pts) have been enrolled. 2 pts have demonstrated a definitive change in their PSA velocity, 1 pt > 40% regression in their absolute PSA. 2 pts with measurable disease have demonstrated regression of < 20%. Toxicity consisted of grade 1/2: fatigue, mucositis, elevated transaminases, diarrhea and rash. 1 pt continues to receive Rapamycin. Median duration of Rapamycin is 32.5 weeks (4–40+). Conclusion: Rapamycin has been well tolerated with signs of anti-tumor activity observed. Information regarding PSA response and time to progression in association with Rapamycin level will be presented. [Table: see text]
Quality of life in intermediate or high risk prostate cancer patients treated by 3-D external beam radiotherapy and brachytherapy with or without androgen deprivation
Authors: Guix B. , Lacorte T. M. , Guedea F. 
Published: March 2020

14587 Background: To elucidate long-term changes in health-related quality-of-life (HRQOL) outcomes by prospectively re-evaluating a cohort of intermediate- or high-risk prostate cancer patients treated by a combination of 3-D External Beam Radiotherapy (EBRT) and Brachytherapy (BT) with or without androgen deprivation (AD). Methods: A cross-sectional survey was administered to 200 consecutive patients with intermediate (Gleason 7 or PSA 10–20 or T2A-B) or high (Gleason >7 and/or PSA >20 and/or >T2B) - Risk Prostate cancer who were treated by EBRT to the prostate followed by BT to the prostate given either by permanent 125-I seeds (LDR) or high dose rate (HDR) implants before treatment and at 6 months interval during 4 years follow-up. The EORTC CLQ-C30 with the PR-25 module was employed. HRQOL was compared among therapy groups. Comparisons between therapy groups was performed using regression models to control covariates. HRQOL of treatment parameters were evaluated. Distribution of responses for bowel-, urinary- and sexual-related functions were analyzed. Results: 200 patients completed the questionnaires. Significant changes in HRQOL were found depending of the time after treatment. After a temporal decline in HRQOL, an improvement owas found during the first 18 months after end of treatment. Significant improvement in the urinary irritative-obstructive performance (p < 0.006) was found after 6 months post-treatment. Bowel domains worsened after therapies (p < 0,05) but improved after 18 months follow-up (p < 0.02). Overall sexual HRQOL deteriorated depending greatly on treatment (p < 0.008). Patients who were given AD presented a significant lower Sexual Function values, that were difficult to recover after AD cessation (p < 0.007). No differences in HRQOL were found between LDR or HDR BT implants. Satisfaction with either treatment was high. Conclusions: After a decline in HRQOL after treatment, it recovered fully during follow-up. In patients treated by AD, sexual function was the most adversely affected quality-of-life domain. Sexual impairment induced by AD was difficult to recover. These results may be of assistance to men and to clinicians when making treatment decisions, mainly relating AD. No significant financial relationships to disclose.
Retrospective study of patients with advanced upper urinary tract transitional cell carcinoma (UUT-TCC)
Authors: Dufresne A. , Fléchon A. , Pommier P. , Droz J. 
Published: March 2020

14611 Background: UUT-TCC is a rare disease with poor prognosis. The aim of the study was to review retrospectively the outcome of 66 patients treated in a single cancer center. Methods: Clinical records of patients treated between 1993 and 2005 were reviewed to identify treatment modalities and outcome. Results: There were 47 (71%) males, median age was 60 years (range: 40–85) and UUT-TCC was associated with superficial bladder cancer in 14 (21%) patients. Forty-one patients had pT2–4 pN0–2 M0 disease after radical nephro-ureterectomy. Adjuvant treatment was: none for 25 patients, chemotherapy for 6 patients, radiotherapy for 1 patient, chemotherapy then radiotherapy for 9 patients. Twenty-seven patients relapsed after a median time interval of 12 months (range: 2–88). Fifty-two patients had metastatic disease (25 at initial diagnosis and 27 after relapse). Respectively 19 and 33 patients had one or multiple metastatic sites. Sites of metastases were: local in 12 patients, retroperitoneal lymph nodes in 30, liver in 23, lung in 19 and bone in 15. Thirty-six patients received platinum-based chemotherapy, 10 received palliative radiotherapy, 5 received best supportive care, and 1 had surgery. Response rate to chemotherapy was 40% with median response duration of 5.5 months (range: 0.2–18.5). Overall survival was 14.6 months. Conclusion: UUT-TCC has a worse prognosis than bladder TCC. However response to chemotherapy and overall survival seem worse than in metastatic bladder cancer. No significant financial relationships to disclose.
A phase II evaluation of imatinib mesylate (G) in stage M0 prostate cancer (PC) patients (pts) on hormonal therapy (HT) with evidence of biochemical relapse
Authors: Sinibaldi V. J. , Carducci M. A. , Elza-Brown K. , Rosenbaum E. , Denmeade S. , Pili R. , Walczak J. , Garrett-Mayer E. , Moore-Cooper S. , Eisenberger M. A. 
Published: March 2020

14612 Background: Imatinib mesylate (Gleevec, G) is a potent inhibitor of the tyrosine kinases and other signaling mediated events. Preclinical models suggest that G inhibits platelet derived growth factor (PDGF) and stem cell factor (SCF) which are important for prostate cancer growth. This trial was designed to evaluate the safety and efficacy of G in PCA pts on HT with stage M0 disease. Methods: Eligible PCA pts included: stage M0 disease with rising PSA levels while on hormonal therapy, no prior chemotherapy. Planned treatment included G 400 mg PO BID given up to a maximum of 12 months. The statistical endpoint for this trial was the% of pts with a ↓ in prostate specific antigen (PSA) ≥ 50% lasting ≥ 4 wks. A 2 stage trial was designed where the study would terminate if the% of pts meeting the endpoint was not convincingly > 30% with 5% chance for error. Pts with a > 50% rise in PSA from baseline were removed from study. Follow-up included monthly toxicities and PSA (specimens frozen/stored until completion of each 3 months of therapy). Results: From 10/1/02–10/11/04, nine pts were enrolled. Pt characteristics included median: age of 67 years (range 52–80), ECOG performance status of 0 (range 0–1), baseline PSA of 29.6 ng/ml (range 2.69–39.52), # prior hormonal manipulations of 3 (1–5). Prior local therapies included: 1 status post (s/p) RP alone, 2 s/p RT alone, 2 s/p neoadjuvant HT plus RP, 2 s/p neoadjuvant HT plus RT. Two pts had no prior local therapy. Two pts had prior salvage RT, 1 had prior palliative RT. Eight of 9 pts evaluable for response and toxicity. One patient never received treatment. None of the pts had a decline 50% decline in PSA level lasting ≥ 4 weeks. Three of 8 pts (38%) had rapid increases in PSA and 4/8 pts (50%) developed metastatic disease after 3 months of therapy. Only one pt completed 12 months of planned therapy. Grade 3/4 toxicities included: fatigue (25%), rash (25%), arthralgias (12.5%), peripheral edema (25%), depression (12.5%), necessitating dose delays and/or discontinuation of G in 4/8 pts (50%). Conclusions: These data suggest significant toxicity and low clinical benefit. Further evaluation of Gleevec in this pt population is not warranted. No significant financial relationships to disclose.
Robotic-assisted laparoscopic prostatectomy in obese patients: The Columbia University experience
Authors: Levinson A. W. , Samadi D. B. , Collins S. M. , Urdaneta A. E. , Goluboff E. T. , Benson M. C. 
Published: March 2020

14619 Background: In addition to being more likely to be found with more aggressive prostate cancer (PCa), obese patients (OPs) face challenges with treatment options for localized PCa. Several studies have shown that open radical retropubic prostatectomy, pure laparoscopic, and robotic-assisted laparoscopic prostatectomy (RALP) may be associated with increased operative times, blood loss, and even a higher rate of capsular incision. We examined our own experience with the surgical and pathologic outcomes of OPs undergoing transperitoneal RALP at our institution. Methods: We queried the Columbia University IRB approved database for transperitoneal RALPs performed by a single fellowship trained laparoscopic oncologist (DS) for which body mass index (BMI) data was available. We identified patients who met the CDC definition of obese (BMI > or = 30 kg/m2) at the time of surgery. We compared surgical and pathologic outcomes between these OPs and NOPs. Of note, operative time was defined as the time from initial trocar placement to skin closure, and does not include robotic set-up time. Results: BMI data was available for 78% of RALP patients in the database. We identified 22 OPs (mean BMI 32.7 (30.1 to 46.7)) and 112 NOPs (mean BMI 25.6). One patient in each group was converted to open. There were no statistically significant differences in the surgical outcomes of mean blood loss, operative time or length of stay for the OPs vs. NOPs (179cc v. 191cc, 213min v. 221min, and 1.4d vs. 1.7d, respectively). There was no significant difference in preoperative PSA, pre-treatment MSKCC 5yr progression-free probability, pre or post-operative Gleason sum, margin status, or perioperative complications. There was a trend towards increased prostatic volume in OPs vs NOPs (51cc vs 44cc, p = 0.10). Conclusions: Unlike a prior robotic, pure laparoscopic and ORRP series, OPs who received transperitoneal RALP at our institution had no statistically significant increases in blood loss, operative time or perioperative complications when compared to their non-obese cohorts. We believe RALPs may be safely recommended to OPs as an option for treatment of localized prostate cancer. No significant financial relationships to disclose.
Phase II study of xyotax (PPX) for androgen independent prostate cancer (AIPC)
Authors: Khan M. , Sharef S. , Amato R. J. 
Published: March 2020

14624 Background: PPX is a polymer conjugate of paclitaxel. In preclinical studies, PPX has an improved therapeutic profile relative to paclitaxel, in addition demonstrated activity in paclitaxel-resistant tumor models. This study investigates whether single agent PPX can induce PSA responses and increase time to progression in AIPC. Methods: Eligibility included: progressive disease based on at least one of the following: a) 3 consecutive rising PSA levels or b) new or progressive measurable disease, or c) new or progressive metastatic lesions on bone scan. Castrate levels of serum testosterone (≤ 50 ug/l), anti-androgen withdrawal, no more than 1 prior chemotherapy regimen, Zubrod performance status of ≤ 2, neuropathy ≤ grade 1, and adequate organ/marrow function. PPX is administered intravenously over 10–20 minutes without routine premedications, at a dose of 150 mg/m2 every 28 days. Dose modifications are based on nature and grade of toxicity observed. Patients (pts) are restaged every 8 weeks until progression or a maximum of 12 months of therapy. Results: 12 patients (pts) (11 previously treated/1 untreated) have been enrolled to date. 7 of the previously treated pts received prior taxanes. 3 pts continue on treatment. 9 pts have completed a range of 6–28 weeks of therapy. Based on a reduction in PSA of at least 50% and maintained for at least 8 weeks, 2 previously treated pts (1 prior taxotere) responded to treatment. 3 pts demonstrated a delay in their PSA velocity. Adverse events were assessed and included: 1 pt who developed a hypersensitivity reaction, 5 pts with grade 2/3 neuropathy, 5 pts with grade 2/3 leukopenia, 2 pts with grade 3/4 neutropenia and 1 pt with grade 4 thrombocytopenia. Other common reversible grade 1/2 toxic effects have been: nausea, fatigue, elevated LFTs and anemia. 6 pts have required dose reduction. Conclusion: PPX is well tolerated and demonstrates promising activity in patients with AIPC. Efficacy assessments are measured by: absolute PSA response, PSA velocity changes, and toxicity data will be presented. [Table: see text]
Application of the International Germ Cell Consensus Classification (IGCCC) to the Nova Scotia population of patients with germ cell tumors (GCT)
Authors: Maydanski Murphy E. , Douglas J. , Thompson K. , Wood L. A. 
Published: March 2020

14625 Background: The IGCCC is the internationally accepted, clinically based, prognostic classification used to aid in the management of GCT. The goal of this study was to determine if the IGCCC is applicable to a population based cohort. Methods: A retrospective chart review of all patients diagnosed with GCT in NS between 1984–2004 was completed, and IGCCC classification (good, intermediate, poor) was assigned to each patient based on the site of the primary lesion, the presence or absence of non-pulmonary visceral metastases and pre-chemotherapy tumor marker values. Kaplan-Meier estimates of five year progression free survival (PFS) and overall survival (OS) were calculated for each IGCCC group, for both non-seminomatous GCT and seminomatous GCT. Results: The distribution, PFS and OS are shown below. Conclusions: The IGCCC seems applicable to a population-based cohort, with similar distribution of categories, as well as clear prognostic ability. This project was funded by a Norah Stephen Oncology Scholars Summer Studentship Grant from Cancer Care Nova Scotia. [Table: see text] [Table: see text]
Phase I/II study of GM-CSF gene-transduced allogeneic prostate cancer cellular immunotherapy (GVAX IT) in advanced prostate cancer patients made lymphopenic by chemotherapy and infused with autologous peripheral blood mononuclear cells (MC)
Authors: Curti B. D. , Assman I. , Moudgil T. , Ratzow T. , Haley D. , Walker E. , Hege K. , Sacks N. , Urba W. J. , Fox B. A. 
Published: March 2020

14635 Background: GVAX IT has been tested in phase I/ II and is currently being tested in phase III clinical trials of patients (pts) with androgen-independent prostate carcinoma (AIPC). Immunological and PSA responses have been described in men receiving GVAX IT. Preclinical studies have shown that antitumor immune responses induced by GVAX IT could be augmented further by making animals lymphopenic and reconstituting with lymphocytes prior to vaccination. A clinical trial was designed to study the effects of lymphopenic reconstitution in pts with AIPC. Methods: All pts had MC collection by leukapheresis pre-treatment. Study groups were as follows: Arm A - GVAX IT given every two weeks for 6 months; Arm B - Cyclophosphamide (350 mg/m2 IV on days 1–3), MC infusion on day 6, GVAX IT on day 7, then every 2 weeks for 6 months; Arm C - Cyclophosphamide (350 mg/m2 IV on days 1–3) and fludarabine (20 mg/m2 IV on days 1–3), MC infusion on day 6, GVAX IT on day 7, then every 2 weeks for 6 months. Results: Seven pts have been treated thus far and completed at least 2 GVAX IT treatments. Pts had ECOG performance status ≤ 1, castrate testosterone levels, ≤ 1 prior chemotherapy regimen and measurable or evaluable metastatic AIPC. Lymphopenia was induced in all pts enrolled in Arms B and C, with recovery of total granulocytes and lymphocytes within 4 weeks following treatment. Monitoring of humoral and cellular immunological responses is underway and shall be presented. Conclusions: GVAX IT and lymphopenic reconstitution is feasible in men with AIPC. Analysis of clinical and immune response is ongoing. Supported by DAMD grant PC020094 and generous support of Mr. Tom Denhart, the Chiles Foundation and the Murdock Trust. [Table: see text]
A multicenter phase II study of thalidomide in combination with interleukin-2 (IL-2) in patients with previously untreated metastatic renal cell carcinoma (MRCC)
Authors: Farray D. , Clark J. I. , Kuzel T. , Dutcher J. P. 
Published: March 2020

14636 Background: Thalidomide, a drug with immune modulating and anti-angiogenic properties has shown activity in relapsed/refractory MRCC; furthermore, early phase I data of oral thalidomide with subcutaneous low-dose IL-2 showed the combination to be safe. The potential anti-tumor activity of this combination formed the basis of this study. Methods: The aim of this multi-center, open label, phase II study was to determine the efficacy and safety of thalidomide and IL-2 given in combination. Patients (pts) with untreated clear cell MRCC with measurable disease and previous nephrectomy were eligible. Two 6-week cycles of thalidomide and IL-2 were planned. Each cycle consisted of thalidomide started at 200 mg orally daily and titrated to 400 mg daily on the 4th day for 6 weeks; IL-2 was started one week post initiation of thalidomide at a dose of 7mIU/m2 subcutaneously days 1–5 for 4 weeks, followed by 2 weeks off therapy. Therapy was to be continued until progression, if there was at least stable disease (SD). Planned accrual was 53 patients. Results: 11 pts were enrolled. The trial was terminated early due to lack of responses. Median age was 57 years (51–66). All pts had an Eastern Cooperative Oncology Group performance status of 2 or better. The only grade 3 toxicities were fatigue (3 pts), neuropathy (1 pt), anorexia (1 pt), dyspnea (1 pt), edema (1 pt); these required dose reductions as per protocol. There were no objective responses: 3 pts had SD, 8 pts had progressive disease (PD). The 3 pts with SD completed 4, 4, and 6 cycles of therapy respectively; of the 8 pts with PD, 3 completed two cycles, and 5 completed one cycle of therapy. Conclusions: The combination of thalidomide and low-dose IL-2 was well tolerated, but in this trial did not show anti-tumor activity in patients with clear cell MRCC. We thank Celgene for support of this trial. No significant financial relationships to disclose.
Trial of chemotherapy (CHT) plus hormonal therapy an initial treatment for prostate cancer (PC)
Authors: Shu T. , Hernandez J. , Karediy M. , Khan M. , Amato R. J. 
Published: March 2020

14637 Background: The delivery of CHT in a setting of androgen-independent (AI) PC has demonstrated: survival benefit associated with a PSA decline and tolerable toxicity, thus strongly suggesting that disease modifying potential exists. Preclinical data supports the benefit of simultaneous CHT and androgen deprivation (AD). The stage is set for CHT to be given earlier in men with PC. Data suggests a transformation from an androgen-dependent to an AI phenotype is mediated by the expansion of an AI clone already present at the time of AD. If this model is correct, it would be feasible to bring CHT up front when the corresponding tumor burden is minimal. Methods: A course of CHT is defined as 8 weeks (6 on/2 off). The therapy consists of weeks 1, 3, and 5 with adriamycin 20 mg/m2 as a 24 hour intravenous infusion on the first day of every week in combination with ketoconazole 400 mg orally 3 times a day, daily for 7 days. Weeks 2, 4, and 6 treatment consisted of docetaxel 35 mg/m2 intravenously over 1 hour on the first day of every week in combination with estramustine 280 mg orally 3 times a day, daily for 7 days. Hormone therapy, GnRH antagonist, is initiated within the first 6 months of starting CHT. Following the completion of 3 courses of CHT, the addition of casodex occurs. Hormone management then continues for a total of 24 months, and then is discontinued. Patients (pts) are followed every 12 weeks with a PSA, testosterone and routine laboratory evaluation. For those men who have had a PSA recurrence, hormone therapy will be reinitiated. Results: 34 men have been enrolled to date. 47% of the men had no prior local therapy, while the other 35% had surgery, 15% had radiation therapy or 3% had both. 3% had a gleason 6, 41%/7, 26%/8, 27%/9 and 3%/10. 64% of the men presented with bone and/or nodal metastasis. Baseline median PSA was 11.2 (1.0–1065.5). The median PSA reduction to date has been 96% with associated nodal and bone scan improvement. Conclusion: Information regarding PSA response, radiographic outcome, toxicity and results of men who are discontinuing hormones will be presented. [Table: see text]
High intensity focused ultrasound in the treatment of small kidney tumours— The Oxford experience
Authors: Leslie T. A. , Illing R. O. , Kennedy J. E. , Wu M. F. , Ter Haar G. R. , Phillips R. R. , Protheroe A. S. , Cranston D. W. 
Published: March 2020

14645 Background: High-intensity focused ultrasound (HIFU) provides a potential non-invasive alternative to conventional therapies. We have been using the extracorporeal ultrasound-guided Model-JC Tumor Therapy System (HAIFU Technology Company, China) in clinical trials to evaluate the safety and feasibility of treating small renal tumours. Methods: Patients with renal tumours less than 4cm diameter and unsuitable for surgery were treated with HIFU were enrolled into this phase II prospective trial. Treatment was delivered under general anaesthesia in a single session using the Model-JC Tumor Therapy System. Magnetic resonance imaging (MRI) 12 days after treatment provided an initial assessment of response (technical success). Patients are followed-up with further MR imaging at 6 months and one year to gauge technique effectiveness. A total of 14 patients will be included in the trial. Results: Eight patients with kidney tumours have been treated to date. All eight have had pre- and 12-day post-treatment MR imaging. One patient was not included in the analysis as treatment was suspended due bowel interposition in the treatment field during therapy. MRI changes suggestive of kidney tumour response have been seen in 4/7 (57%) cases. Complete ablation has been seen in two cases and partial ablation in two cases. One patient remains disease free 12 months after HIFU. Mild transient discomfort was reported by 4/8 patients (50%), and moderate discomfort in 3/8 (38%) but more severe pain needing opiate analgesia has not been encountered in this series. Minor skin toxicity (1mm blister at the treatment site) was seen in two patients. All patients were discharged the day after the procedure. There have been no adverse effects on renal, haematological or hepatic function. Conclusions: Extracorporeal HIFU has the ability to completely ablate small renal tumours. Our early clinical experience suggests that HIFU treatment of kidney tumours is safe and extremely well tolerated. The reasons for the variability in observed response remain obscure, and reliability of tumour ablation will need to improve before extracorporeal HIFU can be proposed for wider clinical use. [Table: see text]