bluuebunny/crossref_metadata_2025_split huggingface dataset:
Docetaxel (D) and estramustine (E) as first-line chemotherapy for patients (pts) with hormone-refractory advanced prostate cancer (HRPC): Final results of a multicentric phase II randomized trial
Authors: Caffo O. , Sava T. , Comploj E. , Giampaolo M. , Zustovich F. , Segati R. , Sacco C. , Perin A. , Pappagallo G. , Valduga F. 
Published: March 2020

15552 Background: Preclinical data showed a synergism between E and D and several studies supported an advantage in associating E and D. Nevertheless, D is considered a standard treatment for HRPC pts and the role of D+E combination remains controversial. Purpose of this study was to evaluate the activity, in terms of PSA decline (PSA↓), the safety and quality of life (QoL) of D±E in HRPC pts. Methods: Eligibility criteria included: HRPC diagnosis, hormone-refractory advanced disease (PSA progression after at least two hormonal therapy), ECOG PS < 2, adequate renal, hepatic and hematological functions, no prior chemotherapy. Pts were randomized to D 70 mg/m2 IV d1 q3w (arm A) or D 70 mg/m2 IV d1 q3w + E 280 mg/TID PO starting 1 day prior to D, for 5 consecutive days (arm B). The treatments were planned until best PSA response achievement or PSA progression. Toxicity was recorded according to NCIC criteria. Qol was assessed by self-filled questionnaires during the treatment. Results: Between 04/2003 and 09/2005, 95 pts (median age 69 years, range 48–86, median PSA 80 ng/ml, range 5–2,166 and measurable disease in 45) were randomized to arm A (49) or arm B (46). In arm A, pts received 321 cycles (median 6, range 0–28) with only 13 (4 %) delays = 7 days. In arm B, pts received 338 cycles (median 7, range 0–20) with only 16 (4.7%) delays. Grade 3–4 hematological toxicities consisted of neutropenia, 4% in arm A and 6% in B. One pt in arm B had febrile neutropenia and grade 3 diarrhea. Grade 3–4 non-hematologic toxicities were vomiting (1 pt in both arms), stomatitis (1 pt in arm A and 2 pts in B) and diarrhoea (1 pt in arm B). Two cases of stroke were reported in arm A. No treatment related death was recorded. Responses, in terms of PSA↓ >50% were: 40% in arm A and 75%in arm B with PSA normalization in 5% and 32% respectively. After a median follow-up of 17 months, 65 patients are died (31 in Arm A and 34 in Arm B). Progression free survival (biochemical) was 20 weeks in arm A and 30 in B. Conclusions: D-based regimens are active in HRPC with a manageable toxicity profile. From this preliminary data, DE combination appears promising, in terms of activity and tolerability so, front-to-front formal comparison in a phase III trial can be recommended. No significant financial relationships to disclose.
A set of nomograms predicting acute gastrointestinal syndrome after prostate cancer conformal radiation
Authors: Valdagni R. , Rancati T. , Fiorino C. , Fellin G. , Vera Righi L. , Magli A. , Mariani L. , Monti A. , Bianchi C. , Vavassori V. 
Published: March 2020

15555 Background: To predict acute toxicities (tox) of the gastrointestinal syndrome (SOMA LENT) in prostate cancer (PCa) patients (pts) undergoing 3D-CRT using a tool (nomogram) with clinical as well as dosimetric variables which has proved to be significant in the AIROPROS 01–02 trial. Methods: Acute rectal tox was scored in 1,132 pts using a 10 item self assessed questionnaire (QST) describing radio-induced GI symptoms profiles for bowel frequency, tenesmus, fecal continence, rectal pain and bleeding. The correlation between hormonal therapy (HT), drug prescription, diabetes or hypertension, pelvic node or seminal vesicles irradiation, mean rectal dose, DVH constraints and rectal tox was investigated by uni- and multivariate (MVA) logistic analyses. MVA results were used the R-project software to create nomograms predicting the symptoms of the acute GI syndrome. Results: 4/10 items of the QST are reported: moderate/severe bleeding, increased bowel frequency, moderate/severe bowel urgency and severe fecal incontinence. Bleeding is related to haemorrhoids (OR=1.9), HT (protective factor, OR=0.78) and mean rectal dose (continuous variable (cv), OR=1.024). Bowel frequency is related to seminal vesicles irradiation (OR=2.8) and V60 (cv, OR=1.024), while bowel urgency is correlated to seminal vesicles irradiation (OR=3.3) and mean rectal dose (cv, OR=1.027). Fecal incontinence depends on seminal vesicles irradiation (OR=4.6) and V70 (cv, OR=1.029). MVA results were used to create a set of nomograms. Conclusions: The combined effect of several independent, prognostically valuable variables for a specific disease can be expressed using nomograms. They can evaluate clinical and technical parameters of the single pt and offer clinicians a tailored probability of a specific outcome. To our best knowledge, this work presents the first set of nomograms available in the literature specific symptoms of the GI syndrome. The prediction capability of these tools will be validated on a independent set of patients. This work was partly supported by Fondazione I. Monzino, Milan No significant financial relationships to disclose.
Determinants of prostate volume changes following iodine-125 interstitial prostate implant
Authors: Bieniek E. , Ashamalla H. , Guirguis A. 
Published: March 2020

15563 Purpose: Prostate brachytherapy (PB) has been linked with increase in prostate volume (PV). This study evaluates post- operative PV changes and the variables that might affect prostate swelling. Methods: Twenty four patients (pts) were analyzed. Twelve were treated with PB only, 8 with external beam radiation (EBRT) prior to implant, and 4 with EBRT after PB. Pre-treatment PSA and Gleason score ranges were 1.9–10.8 and 5–8 respectively. Pre- implant and post-implant day 1, 9, 30, and 60 (PV0, PV1, PV9, PV30, and PV60) measurements were done using computed tomography. Univariate analysis of PV change and the following was done: PV0, number of needles, seeds, and needle insertion attempts, seed activity (0.3 vs 0.5mCi), hormonal ablation therapy, and prior EBRT. Urinary symptoms were assessed using International Prostate Scoring System (IPSS). Results: Ninety six PV measurements were done by a single observer. PV0 ranged from 27.1 to 89.4 cc (mean 48.2). Largest PV was observed on day 1 (40.1–118.7, mean 67.1). Successive PV measurements afterwards continued to decrease. Mean PV values on day 9, 30, and 60 were 58.6, 51.5, and 42.3cc respectively. The differences between PV0 and all successive PV’s were statistically significant. Mean increase in PV1 from PV0 was 18.9±16.8cc (p<0.001), PV0 and PV9 9.7cc, PV0 and PV30 2.6cc. PV60 was smaller than PV0 by an average of 6.6cc. Statistically significant positive correlation was found between PV increase and seed activity (p=0.02) while treatment with EBRT prior to PB was associated with less prostate swelling (p=0.043). Other variables were not significantly correlated with PV changes. Although the mean IPSS score increased from pre-implant value of 9.2 to 13.7 on day 60, the differences between IPSS values were not statistically significant. Conclusions: Maximum prostate size is observed on the first day after implant. Prostate begins to decrease in size between day 1 and day 9 and reaches pre-procedure volume after day 30. Higher seed activity results in greater prostate swelling, while less brachytherapy- induced swelling is observed in patients treated with external radiation prior to implant. Resolution of prostate swelling does not appear to parallel with improvement in urinary symptoms in the first 2 months after implant. No significant financial relationships to disclose.
Sorafenib for the treatment of metastatic renal cancer (MRC) in the real world: The Princess Margaret Hospital (PMH) experience
Authors: Chin S. , Riechelmann R. P. , Wang L. , Tannock I. F. , Berthold D. R. , Moore M. , Knox J. J. 
Published: March 2020

15568 Background: Sorafenib, an oral multi-kinase inhibitor, prolonged progression free survival (PFS) of MRC patients (pts) in second line when compared to placebo in a phase III trial (Escudier at al ECCO 2005). Grade 3/4 adverse events (AE) were reported in 12% of pts. Here we present sorafenib’s efficacy and safety in a less selected cohort of pts enrolled in the Bayer Expanded Access Program at PMH. Methods: Pts with MRC received Sorafenib 400 mg bid continuously until disease progression (PD) and/or clinical deterioration..Tumor response was measured by RECIST criteria. AE were graded by NCI common toxicity criteria. Summary statistics and logistic regression were used to describe the results. Results: From Nov 2005 to Aug 2006, 58 pts were enrolled: median age was 59 years (range 14–86), 47 (81%) were male, 48 (83%) had clear cell histology and 46 (79%) received Sorafenib in first line. None received prior kinase-inhibitors. Using the Motzer Prognostic Index, 29 pts (50%) were low risk, 21 (36%) intermediate and 8 (14%) poor risk. Grade 3/4 AE occurred in 37 pts (64%, 95% CI 50–76%): 15 (26%) pts had skin rash, 10 (17%) hand-foot syndrome, 4 (7%) hypertension, 4 (7%) fatigue, and 4 (7%) diarrhea. Thirty-six (62%) pts required dose reductions and/or treatment interruptions, most due to skin reactions and hand-foot syndrome. Median follow-up was 9 months (IQR range 2–11), the median PFS was 7.5 months (IQR range 5.4–11.3), and the best responses among 56 evaluable pts were: 10 (17%) confirmed partial responses (median duration: 6 months, range 4–11), 14 (24%) stable diseases for = 6 months and 10 (18%) early progression. Pts with bony mets progressed earlier than pts without bony mets. Abnormal creatinine clearance, age, performance status, line of treatment and presence of significant comorbid conditions were not associated with grade 3/4 AE in univariate analysis. Conclusions: Sorafenib is effective in a ”real world”, less selected patient population with MRC but leads to more toxicity than described previously. [Table: see text]
Monocentric evaluation of erlotinib in advanced prostate cancer
Authors: Gravis G. , Gonçalves A. , Bladou F. , Salem N. , Esterni B. , Bagattini S. , Viens P. 
Published: March 2020

15569 Background: The human epidermal growth factor receptor (HER1/EGFR) is known to be over expressed in a variety of cancers, including prostate cancer. Erlotinib is an orally active small molecule tyrosine kinase inhibitor (TKI) targeted against HER1/EGFR (ErbB1). Methods: Pts with advanced or metastatic prostate cancer, adequate organ function and Karnofsky performance status (KPS) ≥ 50% were enrolled in a phase II single institution study. Pts were required to have documented PSA progression before study entry. The primary objective was to determine the efficacy of erlotinib defined as a decrease or stabilization of PSA. Pts received erlotinib 150 mg/day; if no acceptable toxicity was reported in the first 3 weeks, the dose was increased to 200 mg at week 4, and continued until disease progression or unacceptable toxicity. Results: Thirty patients were treated between April 2004 and February 2006, Median age was 69 years (range 51–77) median KPS was 80 (70–100). Median PAL was 85 UI/L (range 33–732), median LDH 224 UI/L (144–1,016) and PSA 102 ng/ml (3, 4–1213). Twenty-eight pts had metastatic disease, 2 had PSA relapse only and 29 were androgeno-independant. Twenty three had received prior chemotherapy (median 2 lines, range (1–7)). Dose escalation was possible in 16 (55%) pts and median duration of treatment was 60 days (14–99). The most common grade 3 toxicities were fatigue (3 ), anaemia (2), diarrhea (2) vomiting (2) cutaneous toxicity (1); one pt. had grade 4 anemia. Median PFS was 29 days (IC 95 [28–33]), median OS 17,38 months. PSA stabilization was observed in 4 pts; no pt had a decrease in PSA. Clinical benefit evaluation based on KPS and pain was achieved in 8 of 20 evaluable pts (40%). Conclusion: Erlotinib demonstrated some activity in advanced prostate cancer with 14% of pts achieving PSA stabilization and 40% a clinical benefit. Erlotinib was well tolerated. Future directions might include evaluating its use in less advanced disease and in pts with EGFR kinase domain mutations. Understanding which biomarkers predict response to erlotinib will likely be important in its application in the metastatic setting. No significant financial relationships to disclose.
Target focal therapy in early prostate cancer: Initial single institution results
Authors: Barqawi A. , Lugg J. , Crawford E. D. 
Published: March 2020

15574 Background: Currently the potential for over- and under-treatment using radical and watchful waiting options respectively constitutes a challenge in the management of patients with early organ-confined prostate cancer. Target focal therapy (TFT) is emerging as an intermediary alternative option for such men. The goal is to provide ablative treatment with minimal impact on morbidity. Methods: As part of an IRB approved study protocol a total of 24 patients initially underwent a 3 dimensional transperineal mapping biopsy under TRUS guidance to confirm the extent of tumor burden and localize the cancer foci within the prostate. Only 12 men qualified to undergo target focal cryotherapy. The remaining patients did not qualify due to upgrading or downgrading of their stage and opted for other treatment options. Follow- up consisted of serial PSA measurements at 3 months interval, disease specific QOL questionnaires, IPSS, and SHIM scores. Results: The mean age was 62.4 years. The mean (SD) prostate size at the time of mapping biopsy was 39 ±14.8g. After mapping biopsy all patients reported time limited hematuria and 2 patients developed urinary retention and were managed successfully with Foley’s catheter for 5 days. Mean PSA before treatment was 5.2 ± 4.1 ng/dl. 10/12 patients had Gleason score (GS) of 3+3, the remaining 2 patients had GS of 3+4. At 3 months follow-up. A median drop of PSA of 1.9 (0, 9.5) ng/dl. All patients reported full urinary continence post operatively. IPSS median drop of 0 (2, -16). Sexual health as assessed by SHIM score showed a median drop of 6 (1, -15) points. In general 4 patients reported a significant change in sexual performance. 2 of which opted for PDE inhibitor with successful regaining of erection at 6 months follow-up. Overall EPIC QOL scores showed no change in rectal, urinary and hormonal components. Sexual component registered a drop of 5 points. Conclusions: The current initial early results appear to be encouraging for future implementation of TFT on select patients with organ confined early stage cancer. Future larger randomized studies are needed to better understand the value of this alternative option in the management of prostate cancer. No significant financial relationships to disclose.
Effect of obesity on overall survival following permanent prostate brachytherapy
Authors: Galbreath R. , Merrick G. S. , Butler W. , Wallner K. , Allen Z. , Adamovich E. 
Published: March 2020

15576 Background: To evaluate the impact of obesity on cause-specific (CSS), biochemical progression-free (bPFS) and overall survival (OS) following prostate brachytherapy. Methods: From April 1995 through March 2003, 1,093 consecutive patients underwent brachytherapy for clinical T1b-T3a (2002 AJCC) prostate cancer. The median follow up was 5.6 years. All patients were implanted at least 3 years prior to analysis. Evaluated body mass index (BMI) subgroups were < 25 (n=258), 25.0 to 29.9 (n=547), 30.0 to 34.9 (n=214) and = 35 (n=74) kg/m2, respectively. Four-hundred and thirty (39.9%) and 589 (53.9%) of the patients received androgen deprivation therapy or supplemental external beam radiation therapy, respectively. Multiple clinical, treatment and dosimetric parameters were evaluated as predictors of CSS, bPFS and OS. Results: The 11 year CSS, bPFS and OS for the entire cohort were 97.5%, 95.6% and 77.6% respectively. BMI did not impact CSS or bPFS for any of the BMI cohorts. However, OS was statistically lower in patients with a BMI < 25 kg/m2 (p = 0.014). A Cox linear regression analysis demonstrated that Gleason score was the best predictor of CSS while percent-positive biopsies, risk group,V100 and hypertension predicted for bPFS. Patient age and tobacco use were the strongest predictors of OS. One-hundred and twenty-eight patients have died with 108 (84.4%) of the deaths the result of cardiovascular/pulmonary disease (73) and second malignancies (35). To date, 12 patients have died of metastatic prostate cancer. Conclusions: Following brachytherapy, obesity did not impact CSS, bPFS or OS. Cardiovascular or pulmonary disease and second malignancies substantially outweighed prostate cancer as competing causes of death. No significant financial relationships to disclose.
The effects of intermittent androgen deprivation therapy (ADT) and zoledronic acid administration on bone density in patients with prostate cancer
Authors: Katznelson L. , Kent K. , Srinivas S. 
Published: March 2020

15593 Background: Intermittent ADT is commonly used in men with recurrent prostate cancer. Bone loss associated with ADT is well described. Bisphosphonate use in men undergoing ADT results in improvement in bone mineral density (BMD), although the utility and duration of bisphosphonate use in men undergoing intermittent ADT are unclear. Objective:To evaluate the effect of zoledronic acid administration every 3 months on BMD in men with prostate cancer undergoing intermittent ADT, and whether BMD is maintained upon discontinuation of both ADT and zoledronic acid. Methods: Patients with recurrent prostate cancer starting ADT were eligible to participate. Subjects received ADT for 9 months in addition to 3 doses of zoledronic acid every 3 months. At 9 months, patients who achieved an undetectable serum PSA were taken off ADT and then randomized either to continuing zoledronic acid every 3 months for an additional 3 doses vs. observation. BMD, assessed by DEXA scan, was determined at baseline, 9 months, and between 18 -24 months at hip, trochanter, femoral neck and lumbar spine sites. Results: Twenty two patients were treated with ADT and zoledronic acid between 2003–2006. Seven of these subjects had bone metastases and had previous treatment with ADT.There was one infusion related reaction, and one patient developed osteonecrosis of the jaw and was removed from the study. At baseline, 3 patients had osteoporosis at the lumbar spine. All patients who received zoledronic acid for 9 months had an improvement in BMD at all 3 sites. In the 7 subjects who had previously received ADT, BMD of the femoral neck increased significantly by approximately 1.9%. Among the 6 patients randomized to continuing zoledronic acid after discontinuing ADT at 9 months, all had a further, significant increase in BMD. Those randomized to observation were unable to maintain their BMD and had continued bone loss despite stopping ADT. Conclusions: This small study demonstrated an increase/maintenance of BMD in men receiving intermittent ADT and zoledronic acid. Only those men who continued zoledronic acid for up to a total of 9 mos after discontinuing ADT maintained BMD No significant financial relationships to disclose.
Chromogranine A and neuron-specific enolase as the main predictors of survival for hormone-refractory prostate cancer (HRPC) patients
Authors: Banu A. , Banu E. , Dionysopoulos D. , Medioni J. , Scotte F. , Levy E. , Oudard S. 
Published: March 2020

15594 Background: Clinical studies suggested that the extent of neuro-endocrine differentiation in prostate cancer increases with tumor progression and the development of androgen refractory status. Chromogranine (CgA) and neuron-specific enolase (NSE) are currently explored as surrogate markers. Methods: Eligible chemonaive HRPC patients (pts) were required to have an ECOG performance status (PS) ≤ 2. Before chemotherapy initiation, we quantified NSE, CgA and PSA in the venous blood using commercial kits. We evaluated the impact of baseline NSE, CgA and PSA on overall survival (OS) using multivariate Cox regression analysis, stratified by chemotherapy regimen. Secondary, we studied the correlation between NSE, CgA, PSA and other important variables as age, Gleason score, hemoglobin, number of metastatic sites and ECOG PS. Results: Data of 39 consecutive HRPC pts treated between December 01–06 in a single French center were analyzed. Chemotherapy was docetaxel-based in 92% of pts. Median age was 71 years (range 51–86) and 79% of pts had bone metastases. Elevated NSE, CgA and PSA were observed in 6, 9 and 30% of pts and median levels were 10.8, 67 and 23.3 ng/mL, respectively. Gleason 8–10 was present in 49% of pts. Significant correlations were observed between NSE and the number of metastatic sites and between CgA and age, hemoglobin and ECOG PS. The baseline PSA was only correlated with Gleason score. Median OS for the entire cohort was 24.4 months (95% CI, 18.8–29.9). Two-year OS was 15% and only 19% of patients are dead. Univariate Cox regression analysis showed only a significant relationship between OS and baseline NSE: hazard ratio= 1.09 (95% CI, 1.03–1.16), P=0.006. No other known prognostic factors are related to outcome. A multivariate model including baseline NSE, CgA, ECOG PS and Gleason score showed a 15% rise of the risk of death related to NSE (borderline P value). Conclusions: NSE was the most powerful predictor of survival for HRPC pts. Our results emphasize the theory that cells secreting NSE are chemoresistant, with a negative impact on OS. No significant financial relationships to disclose.
First-line pemetrexed (P) for the treatment of hormone refractory prostate cancer (HRPC): A phase I/II study
Authors: Lehmann J. , Hack M. , Büttner H. , Stöckle M. 
Published: March 2020

15597 Background: Evaluation of maximum tolerated dose (MTD), efficacy and toxicity of pemetrexed as first-line treatment in HRPC. Methods: Patients (pts) with metastatic and/or unresectable HRPC and progression received P monotherapy 500 mg/m2 i.v. d1 q21d-cycle for 6 cycles with VitB12 and folate supplementation until progression or dose-limiting toxicity. Corticosteroids were given 8 mg p.o. 3 d around P infusion. The primary outcome measure was PSA (serological) response (PSAr), defined as = 50% decline from baseline, confirmed at least 3 wks later. If no metastatic disease, baseline PSA > 5 ng/mL was required. Results: Patient characteristics: 12 pts were treated; median age was 67 yrs (61–76), median baseline PSA 138.6 ng/ml (9.4–2662), median Karnofsky status 95 (80–100). Cycles: A total of 55 treatment cycles was administered with a median of 5 cycles (1–6) per pt. Due to dose limiting toxicities (DLT) during the first cycle in 2/6 pts, P dose was reduced to 400 mg/m2 d1 q21d-cycle for the following 6 pts. One pt experienced a DLT during his first cycle with P 400 mg/m2. Dose needed to be reduced in 3/12 pts, treatment discontinuation occurred in 6/12 pts. Adverse Effects: 6 of 12 (50%) pts experienced a total of 18 grade 3 events according to CTC criteria, including neutropenia, anemia and pain. 4 of 12 (33%) pts experienced a total of 7 grade 4 events, mainly neutropenia and leucopenia. 1 death occurred after one dose of P 500 mg/m2; relationship to P could not be ruled out. Response: 11/12 pts were evaluable for response. On 500 mg/m2 1 pt showed serological response, 1 partial tumor-response in metastatic lymph-node disease was seen. Overall, 7 patients remained serologically stable (63.6%), 3 PSA progressions (27.3%) were seen. Stable serological status could be maintained for 3–43 wks. Conclusions: P 400 mg/m2 was determined the recommended dose for a potential phase II, with an acceptable toxicity profile in this patient population. Serological stability could be achieved in > 60% of patients for up to 43 wks. However, as no confirmed PSA response was achieved with P 400 mg/m2, in a potential phase II a schedule with P 400 mg/m2 but higher dose-density should be pursued as a first-line approach in pts with HRPC. No significant financial relationships to disclose.