bluuebunny/crossref_metadata_2025_split huggingface dataset:
University of Chicago Consortium phase II study of ispinesib (SB-715992) in patients (pts) with advanced renal cell carcinoma (RCC)
Authors: Beekman K. W. , Dunn R. , Colevas D. , Davis N. , Clark J. , Agamah E. , Thomas S. , Nichols K. , Redman B. , Stadler W. 
Published: March 2020

15573 Background: Ispinesib is a novel kinesin spindle protein inhibitor that has significant antitumor activity in multiple tumor models and has demonstrated preliminary clinical activity in early phase I and II trials. A phase II study of Ispenisib in patients with metastatic RCC who had received at least one prior therapy was thus conducted. Methods: The primary objective was to assess the RECIST based overall response rate (RR) with optimal Simon two-stage design utilizing 10% and 30% RR as the null and alternative hypotheses, respectively. Eighteen pts were to be accrued during the first stage; if 3 or more responses (PR or CR) were seen, an additional 17 pts would be accrued. Further study would be recommended if 7 or more of the 35 total pts had a response. Secondary objectives included toxicity, time to progression, and overall survival. Pts were treated with 7 mg/m2 over one hour on days 1, 8, and 15 every 28 days with radiologic disease re- evaluation every 8 weeks. Results: 19 pts were accrued in 6 months. Baseline characteristics included clear cell histology in 74%, papillary in 11%, and unclassified in 11%; 1 or =2 prior therapies in 37% and 63%; prior immunotherapy in 53%, and prior sunitinib, sorafenib or bevacizumab in 79%; ECOG performance status 0 in 58% and 1 in 42%. 4 patients are too early for radiologic assessment. None of the 15 patients evaluable responded to treatment (95% CI: 0 - 21.8%). Seven patients (47%) experienced stable disease after 8 weeks. One patient experienced grade 3 neutropenia. No other grade 3 or 4 toxicities were attributable to drug. Grade 1 and 2 toxicities included: fatigue (28%), anemia (28%), leukopenia (33%), elevated alkaline phosphatase (18%), anorexia (11%), hyponatremia (11%), dyspnea (11%), headache (11%), and hypoalbuminemia (11%). Conclusions: Treatment with weekly Ispenesib in metastatic RCC is well tolerated but does not lead to objective responses. Under the hypothesis that Ispenesib is a cytotoxic rather than cytostatic agent, further evaluation in patients with metastatic RCC at this dose and schedule is not indicated. Supported by: NCI #N01-CM-62201 No significant financial relationships to disclose.
Macrocytosis in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKI's)
Authors: Khasawneh M. F. , Unnithan J. , Choueiri T. , Rini B. , Dreicer R. , Garcia J. , Wood L. , Elson P. , Bukowski R. 
Published: March 2020

15583 Background: Sunitinib and sorafenib are TKIs with inhibitory activity against a variety of kinases including VEGFR, PDGFR, and cKIT, as well as significant clinical activity in mRCC. Off target toxicity is frequently seen, and in pts treated with these TKIs the development of anemia ± macrocytosis was noted. Further studies were conducted to clarify the frequency and etiology of these findings. Methods: A retrospective review of mRCC patients treated with sunitinib or sorafenib for = 3 months was undertaken. Complete blood count data including RBC indices was recorded at baseline, 3 months, and at the end of treatment. Thyroid function tests (TFTs) were collected, and in selected patients, bone marrow examination was undertaken. Results: Ninety eight pts were evaluated (61 sunitinib-treated, 37 sorafenib-treated). In sunitinib-treated mRCC patients, median MCV levels increased significantly at 3 months compared to baseline (97.1 fL vs. 90.2 fL; p<0.001) and median Hgb levels decreased from 13.4 to 12.8 (p =0.31). In patients receiving sunitinib >12 months, MCV continued to increase throughout treatment. There was no association between increasing MCV and the development of hypothyroidism. In 10 patients discontinuing sunitinib, MCV returned to baseline within 2 to 4 months. The number of patient receiving sunitinib with an MCV > 100 at the beginning, 3 months, and end of treatment were 2, 14 and 40 respectively. Bone marrow examinations performed during sunitinib therapy (n=3) demonstrated hypocellularity (5–10%) with normal trilineage hematopoiesis and no evidence of dysplastic changes. In contrast, sorafenib- treated mRCC patients showed no effects at 3 months on MCV levels (90.7 fL vs. 90.6 fL) but an increase in hemoglobin level (14.0 g/dL vs. 13.2 g/dL p=0.02) . At the beginning of treatment 2 patients had MCV values more than 100, but at 3 months and 12 months none of the patients had MCV values more than 100. Conclusions: Macrocytosis commonly develops in sunitinib-treated, but not sorafenib- treated mRCC pts. The etiology of this finding is unclear, but studies suggest direct effects on bone marrow precursors. Sunitinib-induced macrocytosis appears reversible with drug discontinuation. [Table: see text]
Combination of bevacizumab (B) plus immunotherapy, with interleukin-2 (IL-2) and interferon-α (IFN-α) plus chemotherapy (BIC) in patients with metastatic renal cell cancer (mRCC): Dose-finding phase II trial
Authors: Buti S. , Lazzarelli S. , Simonelli C. , Venturini S. , Spazzapan S. , Lo Re G. , Mattioli R. , Dalla Chiesa M. , Brighenti M. , Passalacqua R. 
Published: March 2020

15586 Background: Treatment with IL-2 and IFN-a is considered as an effective immunotherapy (IT) for mRCC. Bevacizumab (B) proved to have efficacy with different mechanism as regards as IL-2 + IFN-a, and had at least an additive effect with chemotherapy (Ch) in many tumors. On this basis, it is reasonable to search for a synergism between B, IT and Ch. Methods: This is a multicenter dose- finding/phase II study aimed at to investigate: 1) safety, tolerability, dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of the BIC combination; 2) antitumor activity. Dose-finding study comprised 5 escalation dose levels of Ch: Gemcitabine (G) (initial dose 600 mg/m2 to 1,000 mg/m2) followed by 5FU bolus (initial dose 400 mg/m2 to 600 mg/m2) each one on days 1 and 8 every 28 days, associated with fixed doses of B (10mg/kg on days 1 and 15), IL-2 (1 MUI/m2 bid sc on days 8, 9, 15, 16 and 1 MUI/m2/day sc from days 10 to 12 and from 17 to 19) and IFN-a (3 MUI sc on days 10, 12, 17, 19). Three patients were enrolled at each dose level according to Fibonacci statistical method. Phase II study used the reached MTD and was conducted according to two stage Minimax Simon design. Treatment was repetead for a maximum of 6 cycles followed by a maintenance therapy with B and IT until progressive disease (PD). Results: 32 patients were enrolled (male 75%); median age 58 years (range: 28–75): of these, 23 was assessable for toxicity, 14 were pre-treated and 9 not; there was 1 case of DLT (2° level) due to a transitory grade 3 transaminases rising; phase II used the highest dose level of Ch. Grade 3–4 toxicity during all cycles included: neutropenia non febrile (11/23) and 1 febrile, fever in 5; grade 3 toxicity included: thrombocytopenia in 7, asthenia in 4, hypertension in 2, anemia in 2; no bleeding of grade 3–4. So far there are 20 assessable patients for response: 6 (30%) partial response, 8 (40%) stable disease and 6 (30%) PD for an overall disease control rate of 70%. Conclusion: This is the first study that explored the synergy between antiangiogenic therapy, IT and Ch in mRCC. The BIC combination is generally well tolerated and shows promising activity. The Phase II study is currently ongoing and accrual is still open. No significant financial relationships to disclose.
Phase I study of CNTO 95, a fully human monoclonal antibody to αv integrins, docetaxel, and prednisone in hormone refractory prostate cancer patients (HRPCP)
Authors: Chu F. M. , Picus J. , Mata M. , Kopacynski C. , Foster B. , Lang Z. , Beckman R. A. , Dreicer R. 
Published: March 2020

15595 Background: CNTO 95 has demonstrated preclinical antitumor activity through binding to multiple av integrins, resulting in growth inhibition indirectly through anti-angiogenic effects as well as directly by inhibiting tumor cell proliferation. The target, av integrins, has been demonstrated by immunohistochemistry in a large proportion of human prostate cancer tissues. Docetaxel and prednisone have become a standard of care for HRPCP. The primary objective of this study was to evaluate the safety of combining CNTO 95 with this standard. Methods: Patients received day 1 infusions of 75 mg/m2 docetaxel together with twice daily oral prednisone in every 3 week cycles, with weekly infusions of either 5 or 10 mg/kg of CNTO 95 for 7 weeks beginning with the second docetaxel cycle, then CNTO 95 on the days of docetaxel thereafter. Patients were monitored for safety and PSA. Radiologic tumor assessments were performed at least every 4 cycles. Results: Six patients have received docetaxel and prednisone with CNTO 95 at either 5 mg/kg (n=3) or 10 mg/kg (n=3). In the 5 mg/kg group, 1 received 8 cycles then withdrew consent because of fluctuating PSA levels; 1 received 9 cycles then had soft tissue disease progression; and 1 has completed 9 cycles and remains on study treatment. In the 10 mg/kg group, all patients remain on study and have received 7, 6, and 6 cycles of treatment, respectively. There were no unexpected toxicities and only one Grade 3 toxicity (febrile neutropenia) attributed to docetaxel. A 50% decline in PSA occurred in 1 patient treated in the 10 mg/kg group. Conclusions: The combination of standard dose docetaxel and prednisone with 10 mg/kg of CNTO 95 was well tolerated and 3 new patients are planned to be treated with these doses on this study. Further study is warranted. [Table: see text]
Preservation of erectile function after permanent radioactive seed implantation for treatment of prostate cancer
Authors: Steinmetz R. D. , Barrett W. L. 
Published: March 2020

15596 Purpose: Assess erectile function before and after prostate brachytherapy. Materials and Methods: A total 241 patients were treated with permanent I-125 prostate brachytherapy for T1 and T2 adenocarcinoma of the prostate. A retrospective chart review was undertaken to assess erectile function before and after treatment using the scoring system of, 1- complete inability to have erections, 2 - can sometimes have erections sufficient for intercourse with or without medication, and 3 - has normal erectile function. Pretreatment testosterone levels were reviewed for correlation with pretreatment erectile function. Results: The median age was 68. At presentation, the median age of patients with erectile scores of 1, 2 and 3 was 70, 67 and 67 respectively. The median time of follow-up was 48 months. Pretreatment erectile function assessment revealed scores of 1 in 28%, 2 in 27% and 3 in 45% of patients. Median pretreatment testosterone levels were 296 ng/dl in the patients with pretreatment score of 1 compared to 360 ng/dl in patients with a score of 2 and 370 ng/dl in patients with a score of 3. The normal testosterone range for this age group is 165 ng/dl to 830 ng/dl. After 12 months erectile function assessment revealed scores of 1 in 29%, 2 in 42% and 3 in 29% of patients. After 24 months erectile function assessment revealed scores of 1 in 30%, 2 in 41% and 3 in 29% of patients. After 36 months erectile function assessment revealed scores of 1 in 32%, 2 in 45% and 3 in 23% of patients. After 48 months erectile function assessment revealed scores of 1 in 39%, 2 in 36% and 3 in 25% of patients. After 48 months, the median age of patients with erectile scores of 1, 2 and 3 was 75, 69 and 66 respectively. After 60 months erectile function assessment revealed scores of 1 in 32%, 2 in 47% and 3 in 21% of patients. After 72 months erectile function assessment revealed scores of 1 in 24%, 2 in 52% and 3 in 24% of patients. 49% of patients were given sildenafil, vardenafil, or tadalafil to improve erectile function. Conclusion: The rate of potency preservation in this cohort declined in an expected manner after permanent brachytherapy for prostate cancer. No significant financial relationships to disclose.
The impact of varying rectal contours on rectal dose in prostate cancer patients treated with hypofractionated radiation
Authors: Joshua B. B. , Faria S. , Patrocinio H. , DeBlois F. , Duclos M. , David M. , Shenouda G. , Souhami L. 
Published: March 2020

15598 Background: In curative radiation treatment of prostate cancer,the advent of 3DCRT has made a reduction in the incidence of normal tissue toxicities while optimizing tumor control. To optimize 3DCRT, the ICRU has published standard definitions of target volumes and organs at risk such that the tumor can receive the optimal dose with as little as possible dose to the organs at risk. However, the definition of the rectum as an organ at risk in radiation treatment of the prostate varies widely among institutions and so does the report of toxicities. We studied the effect of varying rectal contouring on rectal dose obtained from DVHs in a homogenous group of prostate cancer patients treated with hypo fractionationed radiation. Methods: 71 patients with favorable risk prostate cancer treated with a total of 66Gy in 3Gy/day fractionation.18 MV photons in a 5-field technique was used. None of the patients received hormonal therapy. Their treatment plans were archived and the rectum was re-contoured by a single investigator. 4 different contours were drawn to compare the rectal dose: i) the whole rectum from the anal verge to the recto sigmoid junction (WR); ii) the rectum from 1cm below the PTV to 1cm above (RPTV); iii) the rectal wall (i.e. the inner and outer rectal wall) from the anal verge to the recto sigmoid junction (RW); iv) the rectal wall from 1cm below the PTV to 1cm above (RWPTV) Results: There were significant differences in the median volume, minimum, mean rectal doses and dose to 50% of the volume, (p=0.0001). The whole rectum (WR) is having the lowest and the rectal wall with 1cm above and below the PTV (RWPTV) having the highest in all the parameters. The only parameter not significantly different among the 4 contours is the maximum rectal dose. Conclusion: the varied rectal contouring across different institutions is a possible reason for the broadly different reports of rectal toxicity after prostate irradiation. Our results suggest significant differences in rectal doses with varied contouring. Contouring the rectal wall only and limiting the volume to 1cm above and below the PTV confers the highest mean rectal dose. Comparison of rectal toxicity between institutions can only be meaningful if a consensual volume definition of the organ at risk is agreed upon. No significant financial relationships to disclose.
Planned nerve preservation modifications to reduce positive surgical margins during robotic-assisted laparoscopic radical prostatectomy
Authors: Zorn K. , Gofrit O. N. , Lin S. , Steinberg G. D. , Zagaja G. , Shalhav A. L. 
Published: March 2020

15599 Background: Robotic-assisted laparoscopic radical prostatectomy (RLRP) is increasingly being utilized for the treatment of localized prostate cancer at many centers. The main objective of RLRP is cancer control and preservation of erectile function with reduced positive surgical margin (PSM) rates. We evaluated the effect of a side-specific nerve preservation (NP)protocol which was implemented in June 2006 to help further reduce PSM rates. Methods: Between June-November 2006, 150 consecutive RLRPs were performed using select ipsilateral, NP techniques (interfascial, extrafascial and wide resection) based on pre-operative risk factors (clinical stage, biopsy Gleason score (GS), percentage of core number positive and maximal core cancer percentage). Prior to June 2006, only interfascial and wide resection were performed. The NP protocol, included ipsilateral extrafascial dissection in all patients with GS=7 with non-palpable disease. All patients with GS≤6, non-palpable disease and whose biopsy pathology demonstrated <33% of ipsilateral cores positive for cancer were offered interfascial dissection. Wide resection was performed for patients with palpable disease, GS≥8 and ≥66% of all ipsilateral biopsy cores positive for cancer. Pathological outcomes were compared with the 245 consecutive RLRP cases performed prior to June 2006, where more liberal interfascial NP was performed. Results: Relative to the modified NP group, mean patient age (60 vs 59, p= 0.21), PSA (6.7 vs 6.8, p=0.77), clinical stage (p=0.93), biopsy Gleason score (p=0.51), pathologic Gleason score (p=0.32) and stage (p=0.65) were similar to the control group. Mean total number of positive cores involved with cancer were also comparable between groups (3.5 vs 3.3, p=0.31). Overall PSM rate was significantly lower in the modified NP group (12.6% vs 20.4%,p=0.04). Specific pT2-PSM rates were significantly lower (8.3% vs 15%, p=0.04) while only a trend was observed for pT3-PSM rates (34.5% vs 40.4%, p=0.60) in the modified NP group. Conclusions: Modifying ipsilateral nerve preservation for patients undergoing RLRP, based on specific pre-operative variables has significantly helped further reduce overall and pT2-specific PSM rates. No significant financial relationships to disclose.
Safety and activity of sorafenib in advanced renal cell cancer: A single institution experience
Authors: Bajetta E. , Procopio G. , Verzoni E. , Mancin M. , Pusceddu S. , Bajetta R. , Galassi M. , Gevorgyan A. 
Published: March 2020

15604 Background: Sorafenib is an oral multitargeted tyrosine kinase inhibitor of RAF-kinase and VEGFR2, with antiangiogenic and antitumor activity in pretreated advanced renal cell cancer (RCC). Methods: In our institution, from December 2005 to November 2006, 131 consecutive patients(pts) with advanced RCC received sorafenib 400mg/bid/continuously. Main patient characteristics were: clear-cell cancer 106 pts, papillary-cell 15 pts, cromophobe-cell 3pts, collecting duct carcinoma 3pts, other histotypes 4pts. Previous nephrectomy was performed in 122 pts with median relapse free survival of 23 months (range 3–180 mos). The most common site of disease was lung, whereas 94 pts had 2 or more secondary disease locations. According to Motzer’s prognostic score 85 pts were at low risk, 36 pts and 10 pts at intermediate and high risk respectively . 12 pts were treatment naïve for metastatic disease. 68 and 51pts received one or at least two systemic treatments respectively. Results: Currently, 106 pts are evaluable for safety and objective response. According to the RECIST criteria, the activity of sorafenib in terms of tumor shrinkage was observed in 32 pts(31%) with 10 partial response (9.5%) and 22 minor response (21%) respectively. Stable disease was seen in 42 pts (41%) and progressive disease in 28 pts (26%), 4 pts were not evaluable for response. Overall, 74 pts (72%) had disease growth control. Median duration of response was 8 months and median time to progression was 6.5 mos, median overall survival has not been reached yet. The most common treatment-emergent adverse effects seen in 78% of pts, were grade (G) 1/2 (NCI-CTC) and included hand foot syndrome, rash, diarrhea, fatigue, hypertension and mucositis. Dose modification due to G3–4 adverse event, such as skin toxicity and cardiovascular events, was performed in 35 pts(32%). Conclusion: sorafenib is effective in terms of tumor growth control in untreated as well as in pretreated patients and in different hystotypes of renal cell cancer. Particularly, in heavily pretreated patients the number and severity of drug related toxicity suggests the dose reduction as possible standard therapy. The Authors would like to thank (I.T.M.O) Italian Trials in Medical Oncology for editorial assistance. No significant financial relationships to disclose.
Background variables for the patients with invasive bladder cancer suitable for bladder-preserving therapy
Authors: Miyanaga N. , Akaza H. , Hinotsu S. , Joraku A. , Oikawa T. , Sekido N. , Kawai K. , Shimazui T. 
Published: March 2020

15610 Background: The present study was undertaken to identify the patients suitable for bladder preservation by analysis of our previous studies. Methods: The subjects of this study were all 72 patients with T2–3N0M0 bladder cancer who underwent bladder- preserving therapy in our institute. The therapy involved intra-arterial chemotherapy with MTX and CDDP and concomitant radiotherapy. Results: Of the evaluable 70 cases, complete response was confirmed in 57 cases (81.4%). The median follow-up was 45.3 months. The 5-year cause-specific survival rate was 81 % and the 5-year overall survival rate was 66%. Based on the results of univariate analysis, variables contributing to complete response were selected. In T2 cases, tumor size of 3 cm or less was scored 0 and tumor larger than 3 cm was scored 1, while single tumor was scored 0 and multiple tumors were scored 1. In T3 cases, tumor size of 3 cm or less was scored 0 and tumor larger than 3 cm was scored 1, while G2 was scored 0 and G3 scored 1. The CR rates were 93.8% and 92.6% for total scores of 0 and 1, respectively, and 62.9% for a total score of 2 (P = 0.003; score 0 or 1 vs 2). The overall survival rate was significantly higher in the former group (P = 0.003). Conclusion: Bladder-preserving therapy can be acceptable for cases of single T2N0M0 tumor with a size of =3 cm and for T3N0M0 cases with a tumor size of =3 cm. No significant financial relationships to disclose.
Secular trends in survival in prostate cancer (PC) (1992–2005) in a public hospital in Barcelona: Impact of PSA implementation and hormone-radiotherapy (HT+RT) treatment introduction—An observational study
Authors: Malmusi D. , Carles J. , Bellmunt J. , Macià F. , Llorente J. A. , Serrano S. , Foro P. , Gelabert A. , Albanell J. , Castells X. 
Published: March 2020

15615 Background: There are reports of declines in mortality in several series and countries following introduction of PSA test. With routinely collected data we explore changes over time in PC survival, its correlation with PSA implementation and with the introduction of HT+RT. Methods: From the Hospital del Mar Cancer Registry we selected patients with histological confirmation of PC diagnosed between 1992 and 2005. Clinical and pathological stage, grade, PSA at diagnosis, type of treatment and follow-up until 2005 were available, and patients were grouped in three-years periods. Results: Out of 1,185 registered, 897 patients were evaluable. Median age at diagnosis decreased from 72 in 1992–96 to 70 in 2003–05 (p<.001). Median PSA at diagnosis decreased from 35 μg/ml to 14 μg/ml after 1996. Patients being diagnosed as metastatic changed from 67% before 1997 to 29% in 1997–99. A trend towards lower pathological stage has been observed, although in stage II and III no significant changes in risk group distribution were observed throughout the study period (χ2 =.318). Since 1999 there is a progressive increase in HT+RT indication in stages II and III with a significant decrease in the indication of surgery. There is an improvement in overall relative survival at 5 years before and after 1999, from 67,3% (CI: 60,2–75,2) to 92,9% (CI: 87,3–98,9).The same tendency was found in patients with localized tumour with intermediate and high risk coincidentally with the implementation of HT+RT. Conclusions: An increase in survival of patients with PC has been observed, coinciding with a shift towards lower stages and PSA levels at presentation, suggesting an influence of early detection by PSA. The increase in survival among localized tumors since 1999 could be explained by secular variations in the treatment of PC, as the implementation of HT+RT in patients with intermediate and high risk localized PC. No significant financial relationships to disclose.