bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase II study of single agent abraxane as second-line therapy in patients with advanced urothelial carcinoma
Authors: Sridhar S. S. , Canil C. M. , Eisen A. , Tannock I. F. , Knox J. J. , Reaume N. , Mukherjee S. D. , Winquist E. , Chung A. , Ko Y. J. 
Published: August 2020

e16058 Background: Metastatic urothelial cancer progressing on or after first-line platinum-based chemotherapy is incurable and has a very poor prognosis. There is no standard second-line therapy, but the taxanes including paclitaxel, have previously shown activity. Abraxane (ABI-007) is a novel well tolerated albumin-bound nanoparticle formulation of paclitaxel. The goal of this study was to determine the efficacy and tolerability of single agent Abraxane in the second-line metastatic urothelial cancer setting. Methods: Patients with measureable metastatic urothelial cancer, who progressed on or after first-line cisplatin based chemotherapy were enrolled onto this phase II, two-stage multicenter trial. Patients received Abraxane 260 mg/m2 intravenously every 3 weeks. Clinical evaluation, CBC and blood chemistries were performed every cycle and restaging CT scans every 2 cycles. Results: Fourteen patients have been enrolled to date. Patient demographics: M: F 12:2; mean age 64 (range 45–80); ECOG 0:1:2 4:5:5. A total of 57 cycles, avg 4 cycles/ patient (range 1–9) have been administered. There were three dose delays due to neuropathy, pain, and low neutrophil count respectively. There were two dose reductions due to fatigue and neuropathy. Most frequent adverse events (AE) were fatigue, alopecia, anorexia, cough and joint pain; the most frequent grade 3+ AE were fatigue, joint pain, hypertension, joint stiffness and back pain. Fourteen patients are currently evaluable for best response using RECIST criteria. There have been 5 partial responses (PR), 5 stable disease (SD) and 4 progressive disease (PD). Conclusions: Single agent Abraxane was well tolerated in the 2nd line, cisplatin refractory/resistant metastatic urothelial cancer setting. Preliminary efficacy results are encouraging with a clinical benefit rate of 71% (10 out of 14 evaluable pts having either SD or PR). Stage 1 response criteria have been met and accrual is ongoing to a total of 48 patients. No significant financial relationships to disclose.
The robotic era of radical prostatectomy: A retrospective analysis of patient characteristics in contemporary robotic and open prostatectomy
Authors: Murphy A. , Barlow L. , Mann M. , Badani K. , Benson M. , McKiernan J. 
Published: August 2020

e16061 Background: As new treatment options become available without being tested in randomized controlled trials, trends in the patient populations receiving these novel therapies often emerge prior to the determination of ideal patient selection factors. In the case of robotic-assisted laparoscopic radical prostatectomy (RALRP), biases in patient selection for this relatively new procedure may influence the evaluation of postoperative outcomes in comparison to open retropubic radical prostatectomy (RRP). This study describes the disease-specific characteristics of patients currently undergoing RALRP and RRP in a contemporary fashion at a single institution. Methods: A total of 1,088 patients who had surgery since the inception of RALRP at our institution (2003–2007) were identified for analysis. The cohort was divided into two groups based on surgical technique (RALRP versus open RRP). Characteristics of the patient pool analyzed included age at surgery, Kattan Nomogram (KN) score, preoperative prostate-specific antigen (PSA), Gleason sum (GS) at biopsy, and pathological tumor stage. Unpaired t-tests with Welch correction and Mann-Whitney tests were used to determine the differences in patient characteristics between the two surgical approaches. Results: The median age was 61. The mean preoperative PSA was 6.2, and GS 2–6, 7, and 8–10 of 48.2%, 40.4%, and 11.4%, respectively. 519 and 569 patients underwent RALRP and RRP, respectively. There was a significant difference between GS (p<0.0001) and tumor stage (p=0.002) between patients undergoing the two approaches. There were trends in favor of younger age, decreased preoperative PSA, and better KN scores in the RALRP group, but these observations lacked statistical significance (age: p=0.06, PSA: p= 0.07, KN: p=0.15). Conclusions: Although there is insufficient evidence to declare an overall difference in patient characteristics between these two surgical approaches in our patient population, trends toward lower-risk patients in the RALRP group suggest a series of patient selection forces for this procedure. These observations have the potential to influence the results obtained in retrospective analyses comparing outcomes between RALRP and open RRP. No significant financial relationships to disclose.
Benefit of radiotherapy dose escalation in localized prostate cancer with respect to expression of intrinsic markers of hypoxia
Authors: McVey G. P. , Morgan S. C. , Vergis R. , Corbishley C. , Thomas K. , Cooper C. , Horwich A. , Huddart R. , Dearnaley D. P. , Parker C. C. 
Published: August 2020

e16068 Background: Dose escalation improves the efficacy of prostate cancer radiotherapy (RT) at the cost of increased toxicity. Tumor hypoxia causes radioresistance, so the benefit of RT dose escalation may be greater in more hypoxic cancers. Methods: Cases had localized prostate cancer treated with neo-adjuvant androgen deprivation and radical RT at the Royal Marsden in two randomized trials of dose escalation (64 vs 74Gy). Tumour expression of three markers (vascular endothelial growth factor (VEGF), hypoxia inducible factor-1α(HIF-1α), and osteopontin) was assessed immunohistochemically using a semi-quantitative scale by a uro-pathologist, and analyzed with respect to freedom from biochemical failure (FFBF) using the Phoenix definition. Expression of each marker was dichotomised about the median for analysis of the impact of dose-escalation on outcome. Results: 201 cases with a median follow-up of 7 years were evaluable. Seven-year FFBF was 67% vs 40% (HR: 0.42, 95% CI 0.26–0.7, p=0.001) for 74 Gy versus 64Gy, respectively, among cases with high osteopontin expression, and 70% vs 82% (HR: 1.41, 95% CI 0.53–3.76, p=0.49) for 74Gy vs 64Gy among cases with low osteopontin expression. The benefit of RT dose escalation was similar regardless of VEGF or HIF- 1α expression. Conclusions: These data generate the hypothesis that osteopontin expression could inform RT dose individualisation. If validated, patients with low tumor expression of osteopontin could elect to receive less toxic, standard dose RT. No significant financial relationships to disclose.
Biochemical failure after radiation therapy for prostate cancer: Racial differences
Authors: Chi D. , Hirsch A. E. , Gignac G. A. 
Published: August 2020

e16071 Background: Many guidelines for prostate cancer treatment are based on clinical trials with predominantly white patient (pt) populations. The generalizability of these results assumes similar tumor biology among all races. We set out to examine biochemical failure (PSA failure) rates in a cohort of pts after definitive external beam radiation (EBRT) in the racially diverse population at our institution. Methods: We conducted an IRB-approved retrospective review of pts treated with definitive EBRT from January 2000 to April 2008. We excluded from analysis pts who received brachytherapy, salvage, adjuvant or palliative radiation. Race, country of origin, diagnostic data, pre- and post-treatment PSA, Gleason score (GS), clinical stage (CS), and treatment history were reviewed. CS was based on the original clinician's assessment at time of diagnosis. PSA failures were defined using 1996 ASTRO criteria. Two cohorts were grouped by race: white and nonwhite. Statistical analysis was performed using Fisher's Exact test. Results: One hundred seventy-four pts were treated with definitive EBRT. Forty-four pts were white and 130 were nonwhite. Both cohorts demonstrated similar distributions in GS and CS (see Table ). The white cohort had a high proportion of pts with a pretreatment PSA <10 ng/ml (66%) as compared to the nonwhite cohort (46%). Distribution of race/region of origin is: White 44 (25%), Black-American 78 (45%), Black-Caribbean 28 (16%), Black-African 2 (1%), Hispanic 21 (12%), Asian 1 (1%). Just under 50% of each group received neoadjuvant androgen deprivation therapy. PSA failure rate was 7% for the white cohort and 13% for nonwhite (p = 0.41). Conclusions: In this retrospective analysis, there was no statistical difference among races with regard to PSA failure rates. The PSA and Gleason trends in each cohort were consistent with published data on this topic. Dedicated evaluation of the prognostic value of traditional risk stratification in nonwhite pt populations in a prospective trial is warranted. [Table: see text] No significant financial relationships to disclose.
A phase II trial of gemcitabine(G), capecitabine (C), and bevacizumab (B) in patients (pts) with metastatic renal cell carcinoma (RCC)
Authors: Chung E. K. , Posadas E. M. , Kasza K. , Karrison T. , Manchen E. , Michalak L. , Hahn O. M. , Stadler W. M. 
Published: August 2020

e16072 Background: RCC is resistant to most traditional DNA and DNA repair targeted chemotherapy; although modest response rates to nucleotide analog based therapy, including GC, have been reported. Bevacizumab has activity in RCC. We thus performed a single center phase II trial of GCB in pts with metastatic RCC. Methods: Eligibility included clear cell or unclassified histologies, performance status 0–1, measurable disease, normal organ function and no prior treatment with VEGF binding agents or pyramidine analogs. Following significant hematotoxicity in the first 7 of 8 pts, chemotherapy was modified to G 1,000 mg/m2 (days 1, 8), C 1,000 mg po bid (days 1–14) and B 15 mg/kg (day 1) on a 21 day cycle with disease re-evaluation every 3 cycles. Primary endpoint was objective response rate (ORR) using a Bayesian continuous reassessment method designed to detect an improvement in the ORR from a 15% historical rate to 27%. Maximum planned enrollment = 55. Results: 30 pts enrolled from March 2005-May 2008 of which 29 were evaluable: 1 never treated. Pt characteristics: male 83%, median age 58 (36–82), prior nephrectomy 83%, prior radiation 52%, prior cytokine therapy 28%, prior VEGFR tyrosine kinase inhibitor 69%. MSKCC prognostic group: good 24%, intermediate 66%, poor 10%. 7 pts had a partial response (24%). Median overall and progression free survival were 9.8 mo (95%CI: 6.2, 14.9) and 5.3 mo (95%CI: 3.9, 9.9). Grade 3 or 4 toxicities: leucopenia 17%, neutropenia 31%, thrombocytopenia 7%, anemia 14%, proteinuria 3%, rash/hand foot syndrome 7%, fatigue 21%. Average change in mean arterial pressure after 2 cycles: 5.6 (p = 0.040). Serious adverse events: bowel perforation resulting in death 1 pt (3%), sepsis 1 pt (3%), PE/DVT 3 pts (10%), seizure 1 pt (3%). Conclusions: The trial was terminated early despite not meeting protocol criteria for success or futility due to slow accrual and the fact that the historical response rate on which the trial was based became irrelevant with emerging data using sequential VEGF pathway directed therapies. Nevertheless, the observed progression free and overall survival compare favorably to other phase II trials in this population. [Table: see text]
An open, randomized, multicentre, phase III trial comparing the efficacy of two tamoxifen (T) schedules in preventing gynecomastia (gy) induced by bicalutamide monotherapy (BM) in prostate cancer patients (pca pts)
Authors: Bedognetti D. , Rubagotti A. , Conti G. , Francesca F. , De Cobelli O. , Canclini L. , Gallucci M. , Aragona F. , Di Tonno P. , Boccardo F. 
Published: August 2020

e16080 Background: BM is a valuable option for pca pts who wish to avoid the consequences of androgen deprivation and to mantain sexually active.BM is commonly well tolerated:however gy and mastalgia virtually develop in all pts and represent a major cause of treatment discontinuation. We had previously demonstrated that T is safe and effective in preventing breast events induced by BM without affecting B tumor activity (Boccardo, J Clin Oncol. 2005;23:808). However possible interferences between B and T,especially after prolonged administration, remain a matter of concern.In order to reduce the exposure to T,we considered the putative advantages of a weekly administration based on T effects being dose -dependent and on drug long half-life. Methods: This was a non inferiority trial. 80 pts with localized, locally advanced or biochemically recurrent pca were randomly assigned to receive daily B (150 mg) plus T 20 (mg) continuously (d group: n = 41) or same but with T at 20 mg/weekly after the first 8 weeks (wk group: n = 39). Gy (primary endpoint), breast pain (bp), serum PSA levels and sexual functioning scores were evaluated. Results: At a median F.U. of 24.2 mos (95% CI: 23.7 -24.6) gy developed in 31.7% of pts in d group and in 74.4% of pts in wk group (p < 0.000). Bp occurred in 12.2% and 46.1% of pts respectively (p = 0.008) and it was more severe in patients switched to weekly T. The incidence of Aes was comparable (d group:58.8%;wk goup: 56.4%). However most events were mild and easily manageable. There were no major differences among treat. schedules relative to sexual functioning scores, PSA behaviour and disease progression. Conclusions: This study failed to demonstrate that it might be possible to maintain comparable prophylactic effect of T by switching from a daily to a weekly schedule and confirms that T at the daily dose of 20mg is safe and effective in preventing the incidence and severity of BM induced breast events. No significant financial relationships to disclose.
Quality-of-life and LhRH agonist therapy among prostate cancer patients following PSA failure
Authors: Undevia-Yedavalli N. , Dandade N. , Luu T. , Samaras A. , Sartor O. , Nonzee N. , Bennett C. 
Published: August 2020

e16083 Background: Growing numbers of prostate cancer patients experience biochemical relapse (PSA failure) after initial treatment. LhRH agonist (hormonal) therapy can reduce PSA levels, but there is no clear evidence that it slows disease progression or reduces mortality. Quality of Life (QoL) issues are essential when deciding between observation (OBS) versus hormonal castration following biochemical relapse. We evaluated health related quality of life and treatment satisfaction among prostate cancer patients who experience PSA failure. Methods: Eligibility criteria were receipt of primary therapy for prostate cancer followed by a PSA nadir and subsequent PSA rise to at least 0.2 ng/ml. Data sources include medical records and interviewer administered surveys on health- related QoL at baseline, 3 and 12 months. Results: Castrated versus observed patients who are satisfied with their sexual activity report similar health-related QoL, with the exception of higher rates of maintaining an erection (73.3% vs. 32.0%) and not having prostate cancer affect sexual activity (66.7% vs. 28.6%). Castrated and expectant management patients with low levels of satisfaction and sexual activity report similar health-related QoL. Conclusions: Among patients with PSA Failure, the only health-related QOL difference is reflected in sexual activity related to erectile dysfunction, but not sexual satisfaction among patients who all have a high level of treatment decision satisfaction and sexual activity. [Table: see text] [Table: see text]
Docetaxel and imatinib every 21 days for castration resistant prostate cancer: A phase II trial
Authors: Gillison T. L. , Appleman L. J. , Friedland D. M. , Evans T. L. , Lara P. N. , Gooding W. E. , Lenzner D. E. , Strausser H. M. , Gingrich J. R. , Chatta G. S. 
Published: August 2020

e16086 Background: Docetaxel (D) IV every 21 days, is the only cytotoxic agent that prolongs survival in men with castrate resistant prostate cancer (CRPC). Imatinib (I), a tyrosine kinase inhibitor, modulates PDGFR-ß in tumor vasculature. Based on phase I data from our institution, we hypothesized that D plus I would prolong time to progression (TTP) in patients (pts) with CRPC. Methods: Subjects with CRPC received D 60 mg/m2 IV every 21 days plus I 400 mg PO daily. After 10 pts, the study treatment was modified due to toxicity so that pts received I 400 mg on 10 of 21 days/cycle. The primary endpoint was TTP. Secondary endpoints were rate of PSA response and overall survival (OS). The sample size of 43 pts was designed to provide 90% power to detect an increase in TTP from 5 to 8 months. Results: 43 pts enrolled from 8/05 to 9/08. Age at enrollment ranged from 54–86 years (median 69 years). 14 pts received <1 cycle of D plus I and were unevaluable: 10 had significant toxicity, 4 due to non-treatment related reasons. Primary toxicities were hematologic: 21% G4 neutropenia, 5% G4 anemia, and no G4 thrombocytopenia. Fatigue, nausea, diarrhea, and electrolyte abnormalities were common, but <2 cases each of G3-G4 toxicity occurred. 1 case of G5 non-neutropenic sepsis occurred. 29 pts received >2 cycles of chemotherapy (mean 4.6). 12 pts had PR (41.4%), 9 had SD (31.0%), and 8 had no response (27.6%) by PSA. No objective responses were seen by CT imaging among 10 pts with measurable disease. 3 pts remain on trial. For evaluable pts, overall median TTP was 6.4 months (95% CL: 4.8, 8.4 months) compared with TTP of 5 months seen in previous trials. 23 (79%) pts had PSA progression, 3 pts died before progression, and 3 pts remain on trial. For all evaluable pts who had PR or SD by PSA (N = 21), median TTP was 7.1 months (95% CL: 5.5, 9.1 months). Median OS was 23.1 months (95% CL: 11.61 months, NR), compared with 18.9 months for GC Conclusions: Docetaxel on day 1 plus imatinib 10 days of each 21-day cycle resulted in meaningful improvement in TTP in the subset of pts who showed a response. Toxicity precludes its use in the general population, although its role in select pts with good performance status needs to be explored. [Table: see text]
Results at 5 years of intra vesical gemcitabine (G) single agent as adjuvant chemotheray in superficial transitional cell carcinoma (TCC) of the bladder
Authors: Smaili F. , Bounedjar A. , Ferhat R. , Bouzid K. 
Published: August 2020

e16087 Background: Systemic intravenous gemcitabine is usually used in advanced bladder carcinoma, intravesical G is a novel treatment approach for TCC. In this study we evaluate the efficacy of intravesical Gemcitabine in patients (pts) with superficial bladder carcinoma. Methods: From February 2003 to June 2004, 60 pts (57M/3F) were enrolled in the study (M/F = 57/3). The median age was 59,5 years old (24–84). Nine pts had a carcinoma in situ (Cis) and 51 had pT1 lesions. Three weeks after a total transurethral resection (TUR), patients receive intravesical instillation of 2000 mg G every week for 6 weeks, than every month for six months. They received a total of 720 instillations, Follow up was with cystoscopy and urine cytology every six months. Results: At a median follow-up time 60 months, all patients were evaluable for tumor response: 23(38, 3%) patient had a persistant complete remission after treatment, 26 patients (43,3%) had a superficial relapse of TCC, six patients (10%) had progressive disease: four with muscle invasion and two with distant metastasis. Conclusions: Intravesical therapy with gemcitabine is active and well tolerated treatment in patients with superficial TCC carcinoma of the bladder. A phase III trial comparing GEM with intravesical BCG or MMC is warranted No significant financial relationships to disclose.
The effect of naturopathic and nutritional supplement treatment on tumor response, control, and survival in prostate cancer patients treated with radiation therapy
Authors: Birdsall T. C. , Cain L. , Martin J. , Birdsall S. M. , Wiersum L. , Anderson K. , Eden B. , Flynn J. , Kelly D. , Braun D. P. 
Published: August 2020

e16088 Background: Potential antagonism of clinical response to cancer treatment by naturopathic/nutritional supplements (NNS) with anti-oxidant activity has been suggested. This study assessed effects of NNS on tumor response to radiation therapy (RT) in prostate cancer patients (PCpts). Methods: Of 134 RT-treated PCpts with localized tumors, 69 received NNS (+NNS; median age=62.0 yrs) and 65 did not (-NNS; median age=61.5 yrs). Based on pre-RT PSA, 52low (4–10 ng); 13 intermediate (10–20 ng); and 4 high risk (> 20 ng) PCpts were +NNS and 50, 10, and 5 low, intermediate & high risk PCpts were -NNS. Tumor stages for +NNS were T1c (39%); T2a (44%); T2b (10%); T2c (5%) with 1 T3b tumor and were T1b (3%); T1c (46%); T2a (32%); T2b (12%); and, T2c (5%) with 1 T3a tumor for -NNS cohorts. RT consisted of external beam therapy (4500–5000 cGy) + HDR brachytherapy (600–650 cGy/fraction x 2–3 fractions) administered over 6–8 weeks. NNS regimens (range 1–7 antioxidants) included Green Tea Extract, Melatonin, high-potency multivitamins, vitamin C, and vitamin E. All pts were monitored ≥ 24 months post RT. Hormonal therapy (HT; oral bicalutamide (50 mg/day) ±leuprolide depot (22.5 mg IM q 3 months) as neoadjuvant or adjuvant HT was given to 39 (57%) and 38 (58%) PCpts in the +NNS and -NNS cohorts respectively. Results: For the +NNS cohort that did not receive HT, PSA levels were 5.05; 0.285; and 0.356 ng at pretreatment, nadir and ≥ 24 months followup respectively with PSA nadir at 27 months and median followup of 36 months. The corresponding values for the -NNS cohort were 5.6, 0.54, and 0.585 ng with PSA nadir at 25 months and median followup of 29.6 months. Differences were not statistically significant. For the +NNS cohort that did receive HT, PSA levels were 6.8, 0.03 and 0.12 ng at pretreatment, nadir and ≥ 24 months followup with median time to nadir = 4.3 months and median followup = 29.2 months. Corresponding values for -NNS cohort were 6.9, 0.03, and 0.11 with median time to nadir = 3.6 months and median followup = 30.5 months. Differences were also not statistically significant. Conclusions: This study shows that NNS with antioxidant activity do not interfere with clinical response to RT ± HT as definitive treatment for limited stage prostate cancer. No significant financial relationships to disclose.