bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase II trial of the multi-kinase inhibitor sorafenib versus interferon (IFN) in treatment-naïve patients with metastatic renal cell carcinoma (mRCC)
Authors: Escudier B. , Szczylik C. , Demkow T. , Staehler M. , Rolland F. , Negrier S. , Hutson T. E. , Scheuring U. J. , Schwartz B. , Bukowski R. M. 
Published: March 2020

4501 Background: Sorafenib, an oral multi-kinase inhibitor that targets tumor growth and vascularization, significantly prolonged PFS in a Phase III trial with previously treated mRCC patients. This randomized Phase II trial investigated the efficacy and tolerability of sorafenib compared with IFN in first-line therapy of patients with clear-cell RCC. Methods: Untreated patients with mRCC were stratified by MSKCC prognostic score and randomized to receive continuous oral sorafenib 400 mg bid or IFN 9 million units tiw, with an option of dose escalation (600 mg bid sorafenib) or crossover from IFN to sorafenib upon disease progression. The study assessed PFS at 99 events as primary objective, best response (RECIST), overall survival, health-related quality of life, and adverse events (AEs). Results: Baseline characteristics of 188 patients (sorafenib n=97; IFN n = 91) were: median age 62.0 years; MSKCC score: 57% low, 41% intermediate, 1% high; prior nephrectomy: 82%; ECOG 0:1, 55.3%:44.7%. As of January 6, 2006, PFS events have been reported for 64 (34%) patients. Preliminary data showed drug-related AEs of any severity (sorafenib vs IFN) in 50.5% vs 51.6% of patients (≥grade 3: 8.2% vs 11.0%), including diarrhea (24.7% vs 5.5%), fatigue (14.4% vs 20.9%), fever (2.1% vs 18.7%), hypertension (13.4% vs 0%), nausea (5.2% vs 13.2%), flu-like syndrome (1.0% vs 6.6%), hand-foot skin reaction (6.2% vs 0%), and rash/desquamation (4.1% vs 0%). Drug-related metabolic/laboratory abnormalities at grade 3 (no grade 4) comprised hypophosphatemia (21.7% vs. 0%), lipase elevation (5.6% vs. 11.1%), anemia (0% vs. 5.3%) and hypoalbuminemia (0% vs. 3.6%). Five patients receiving IFN withdrew from treatment due to AEs, whereas only one patient withdrew from sorafenib. Conclusions: Sorafenib was generally well tolerated in RCC patients in the first-line setting, with relatively infrequent drug-related AEs ≥grade 3. Full PFS data will be presented at the meeting. [Table: see text]
Bony metastatic disease responses to sorafenib (BAY 43–9006) independent of PSA in patients with metastatic androgen independent prostate cancer
Authors: Dahut W. L. , Scripture C. D. , Posadas E. M. , Wu S. , Arlen P. M. , Gulley J. L. , Wright J. , Chen C. C. , Jones E. , Figg W. D. 
Published: March 2020

4506 Background: Sorafenib is a novel bis-aryl urea, multi-kinase inhibitor, approved for the treatment of advanced renal cell carcinoma. It inhibits b- and c-Raf kinase, PDGFR, c-kit, VEGFR, Flt-3 and p38 and demonstrates anti-proliferative and anti-angiogenic activity. Studies have shown a role for anti-angiogenic therapy for androgen-independent prostate cancer (AIPC). Evidence suggests that the Ras-Raf-MAPK-ERK signaling pathway is dysregulated in AIPC and might be targeted by sorafenib. Methods: 22 patients (pts) with progressive metastatic AIPC enrolled in an open-label, single arm phase II study. The primary objective was to determine if sorafenib is associated with a 50% 4 month probability of progression free survival as determined by clinical, radiographic, and PSA criteria. Sorafenib was given continuously at a dose of 400 mg orally twice daily in 28-day cycles. Clinical assessment and PSA measurement occurred every cycle with radiographic measurements every 2 cycles. Results: Baseline patient characteristics included a median (range) age of 64 (51–78), Gleason 8 (6–9), PSA 226.4 ug/l (2–1905), Alk Phos 108 u/l (48–259), Hb 12.7 g/dl (10.2–15.1). 60% of patients had received one prior chemotherapy regimen. Of the 19 pts with progressive disease, 10 progressed only by PSA criteria in the absence of evidence of clinical and radiographic progression. Two pts were found to have dramatic disappearance of bone metastatic lesions as demonstrated by bone scan, even though they met PSA progression criteria at the time the scans were obtained. Toxicities likely related to treatment include: one grade 3 hypertension and hand-foot syndrome; grade 1/2 toxicities: fatigue, anorexia, hypertension, skin rash, nausea, and diarrhea. Conclusion: Sorafenib in AIPC is relatively well tolerated with 2 patients demonstrating evidence of improved bony metastatic lesions. Interpretation of this study is complicated by discordant radiographic and PSA responses. PSA may not be an adequate biomarker for monitoring sorafenib activity. Further study of sorafenib in metastatic AIPC using clinical and radiographic endpoints is warranted. No significant financial relationships to disclose.
Long-term outcomes after local treatments for prostate cancer by functional categories: Late changes, different results
Authors: Chen R. C. , Clark J. A. , Mitchell S. P. , Talcott J. A. 
Published: March 2020

4507 Background: Although patient-reported treatment outcomes have gained wide acceptance, numerical changes in validated instruments are difficult to interpret by patients and physicians. Using functional categories derived from numerical scales, we report 24- and 36-month outcomes after treatments for localized prostate cancer, presented by patients’ baseline (pre-treatment) functional status, to provide more useful prognostic information and to identify further changes in the third year after treatment. Methods: Using validated symptom indices, we prospectively measured sexual, urinary, and bowel functions of 438 men at baseline, and at fixed intervals post treatment. We translated numerical scores into functional categories: good (normal), intermediate, and poor (severe dysfunction). Results: Abnormal baseline function and surgery in men with normal function uniformly produced poor sexual function ( table ), and more external beam radiotherapy (EBRT) and brachytherapy (BT) patients deteriorated between 24 and 36 months. For those with normal urinary continence, NNSRP (non-nerve sparing radical prostatectomy) produced poor outcomes (26%) more frequently than NSRP (9%) at 24 months and 36 months, despite improvement in some NNSRP patients. Severe incontinence was rare after EBRT (1%) and BT (3%), though slightly more frequent in EBRT patients by 36 months. For patients with normal bowel function, EBRT and BT caused worse outcomes than RP; no change occurred after 24 months. Conclusions: Abnormal baseline sexual function and surgery produced uniformly poor sexual function outcomes and poor function increased significantly between 24 and 36 months after radiation therapy. Significant changes in functional category occurred despite unchanged average numerical scores, indicating that stable numerical indices may conceal significant functional changes. [Table: see text] No significant financial relationships to disclose.
One course of adjuvant PEB chemotherapy versus retroperitoneal lymph node dissection in patients with stage I non-seminomatous germ-cell tumors (NSGCT): Results of the German Prospective Multicenter Trial (Association of Urological Oncology [AUO]/German Testicular Cancer Study Group [GTCSG] Trial 01–94)
Authors: Albers P. , Siener R. , Krege S. , Schmelz H. , Dieckmann K. , Heidenreich A. , Kwasny P. , Pechoel M. , Lehmann J. , Fimmers R. , Hartmann M. 
Published: March 2020

4512 Background: The incidence of relapse was analyzed in patients with clinical stage I (CS I) NSGCT after either retroperitoneal lymph node dissection (RPLND) or one course of adjuvant cisplatin, etoposide, and bleomycin (PEB) chemotherapy. Methods: Between September 1996 and February 2005, 382 patients with stage I NSGCT were included in the German Prospective Multicenter Trial. After orchiectomy, patients were randomized to either RPLND (191 patients) or one cycle of cisplatin 20 mg/sqm d1–5, etoposide 100 mg/sqm d1–5, and bleomycin 30 mg d1, 8, 15 (PEB, 191 patients). Pathological stage II after RPLND (18% of CS I) was followed by adjuvant chemotherapy (2 × PEB). The primary endpoint was relapse rate. The trial was powered to show an advantage for chemotherapy (planned sample size 360 patients, alpha 5%, power 80%) after a median follow-up of 3 years. Results: Thirty-six patients were excluded due to violation of the inclusion criteria. Of the remaining 346 eligible cases, 172 patients were treated by RPLND and 174 patients received one course of PEB. Median time of follow-up was 47 months, with 323 patients (93%) followed-up for at least 1 year. Of the evaluable patients 331 (96%) have remained disease-free. Thirteen (8%) patients experienced relapse after RPLND and 2 (1%) after one course of adjuvant PEB (p = 0.0028). All patients with relapse have been successfully treated. Five patients developed pulmonary metastases, 3 patients relapsed with retroperitoneal metastases, 3 patients showed marker elevations, and 2 patients had an inguino-scrotal relapse after RPLND. The patients with one cycle of PEB relapsed with a tumor marker elevation and a mature teratoma retroperitoneal metastases, respectively. Conclusions: This randomized trial revealed only two relapses among 174 patients treated with one course of PEB. The low risk of recurrence supports one course of PEB over RPLND for the treatment of patients with clinical stage I NSGCT. No significant financial relationships to disclose.
Randomized phase III trial of sorafenib in advanced renal cell carcinoma (RCC): Impact of crossover on survival
Authors: Eisen T. , Bukowski R. M. , Staehler M. , Szczylik C. , Oudard S. , Stadler W. M. , Schwartz B. , Simantov R. , Shan M. , Escudier B. 
Published: March 2020

4524 Background: Sorafenib was approved for advanced RCC in the USA December 2005. A Phase III randomized double-blind, placebo-controlled trial demonstrated an estimated 39% improvement in survival for patients receiving sorafenib versus placebo (HR= 0.72, p = 0.018) (ECCO 2005). These data supported independently reviewed doubling of PFS to 24 weeks in RCC patients receiving sorafenib compared with placebo (12 weeks) (p < 0.000001) (ASCO 2005). Based on the statistical significance and magnitude of PFS benefit, patients were unblinded and placebo patients allowed to crossover to sorafenib in April 2005. A prospectively planned interim OS analysis reflecting impact of crossover of placebo patients is presented. Methods: OS data up to November 30, 2005, were analyzed in this interim analysis using a stratified log-rank test comparing the two treatment groups. In order to examine the effect of crossover on OS, a secondary analysis was performed censoring data from patients randomized to placebo at June 30, 2005. Results: A total of 903 patients were randomized (451 to sorafenib, 452 to placebo) and >200 placebo patients crossed over to sorafenib. Baseline characteristics were similar between treatment arms. There were 367 deaths. The median OS was 19.3 months for sorafenib versus 15.9 months for placebo (HR = 0.77; 95% CI 0.63, 0.95; p = 0.015); although this did not attain the level of significance specified for the interim analysis (α = 0.009), a continued favorable trend in survival benefit was observed. With censoring of crossover data, the median OS was 19.3 months for sorafenib versus 14.3 months for placebo (HR = 0.74, 95% CI 0.58, 0.93; p = 0.010). Conclusion: Sorafenib is the first novel, oral approved treatment for advanced RCC in more than a decade. Previous information on the effect of crossover on OS in randomized oncology studies is limited. The lower HR observed after censoring placebo patients crossed over to sorafenib suggests a continued beneficial effect of sorafenib. Final results await more mature data. [Table: see text]
A comparison of quality of life and symptoms in kidney cancer patients receiving sorafenib versus placebo
Authors: Dhanda R. , Gondek K. , Song J. , Cella D. , Bukowski R. M. , Escudier B. 
Published: March 2020

4534 Background: Results from the Phase III TARGETs study showed that sorafenib significantly prolonged progression-free survival compared with placebo in patients with advanced renal cell carcinoma. Overall survival was longer with sorafenib than placebo with a hazard ratio of 0.72. The impact of sorafenib treatment on health-related quality of life (HRQL) and symptoms was also evaluated. Methods: HRQL was measured by the Functional Assessment of Cancer Therapy-General (FACT-G). Symptoms were measured by the FACT-Kidney Cancer Symptom Index (FKSI), in which patients used a Likert scale (0–4) to respond to each of 15 items. FACT-G and FKSI were administered at baseline, at Day 1 of each cycle, and at end-of-treatment visit. Statistical analyses used a random coefficient model over five cycles, using MSKCC risk and treatment as factors and baseline score and relative days as covariates, adjusted for multiple comparisons with Bonferroni correction. Results: A total of 903 patients were randomized. The FACT-G completion rates at baseline, and Cycles 2, 3, 4, and 5 were; 96%, 91%, 95%, 99%, and 100%, respectively. The FKSI completion rates were; 94%, 89%, 94%, 97%, and 100%, respectively. The completion rate within each patient reported outcome (PRO) measure, across all visits, was 93%. At baseline, there was no between-treatment difference in score for either FACT-G or FKSI. There was no treatment difference after adjusting for multiple comparisons in mean FACT-G total score (p = 0.96) or its domains (physical well-being [p = 0.92]; emotional well-being [p = 0.46]); social well-being [p = 0.75]; functional well-being [p = 0.94]), and no difference in total score of FKSI over time. FKSI single-item analysis showed that sorafenib-treated patients had significantly less symptoms vs placebo (e.g. cough [p < 0.0001], fevers [p = 0.0015], ‘worry that condition will worsen’ [p = 0.0004], shortness of breath [p ≤ 0.0312], and ‘ability to enjoy life’ [p = 0.0119]). Only ‘concern about treatment side-effects’ favored placebo patients (p < 0.0001). Conclusions: Sorafenib demonstrates clinical benefit without adversely impacting overall HRQL, and has a positive impact on individual symptoms. [Table: see text]
Is intravenous (iv) IL2 superior to subcutaneous (sc) IL2 in good prognosis patients (pts) with metastatic renal cell carcinoma (MRCC) receiving a combination of IL2 and alpha interferon (IFN)? Results of the prospective randomized PERCY Duo trial
Authors: Negrier S. , Perol D. , Ravaud A. , Bay J. O. , Oudard S. , Fargeot P. , Delva R. , Deplanque G. , Gravis G. , Escudier B. 
Published: March 2020

4536 Background: Pts with a single metastatic site are more likely to benefit from an IL2 and IFN combination (Negrier NEJM 1998). The French Immunotherapy Intergroup designed a multicenter trial to assess the potential benefit of iv over sc IL2 in IL2+IFN combination in this subgroup. Methods: Untreated pts, Karnofsky score ≥ 90 and a single metastatic site were randomized into this 2 arm trial. Pts received continuous IL2 infusion (18 million IU/m2/d) (arm A), or sc IL2 injections (9 or 18 million IU) twice daily (arm B). IFN was given sc (6 million IU) 3d/week in both arms. Tumor responses (OMS criteria) were assessed at weeks 12 and 27. The primary endpoint was overall survival (OS), with an expected difference of 15% at 4 yrs in favor of iv IL2. The planned sample size was 220 to have 80% power at 5% significance level with a one-sided test. One intent-to-treat analysis was performed and survivals were compared using log-rank tests. Results: From January 00 to January 05, 80 and 75 pts were randomized to arms A and B respectively. Enrollment was stopped early due to low accrual; analysis was performed at 40-month median follow up. Patient characteristics were well balanced between groups. Median age was 55, 82% pts were male, 68% had lung metastases, and 37% had more than 1 year from renal tumor to metastases. No toxic death occurred, gr 3/4 vomiting, rise in creatinine level, hypotension and neurologic toxicity were significantly higher in arm A. Response rates were 17.9 vs 21.3%, in arms A and B, respectively. Progression-free survivals were not significantly different (P: 0.285). The difference in OS was not significant: median 37.7 months [95%CI: 28.2–58.4] with iv IL2 vs. 26.3 [95%CI: 24.5–34.2] with sc IL2 (P: 0.127). Conclusions: Iv IL2 combined with IFN confers no significant advantage over a sc IL2 combination in selected pts with good prognosis MRCC. Since some toxicities were significantly more frequent with iv IL2, the use of this combination cannot be recommended. Because of premature stop, the trend in favor of iv IL2 should encourage further studies before final conclusions can be drawn. [Table: see text]
Stage one seminoma: Evidence based guidelines for follow up
Authors: Martin J. M. , Panzarella T. , Zwahlen D. R. , Chung P. W. , Warde P. 
Published: March 2020

4546 Background: Several management strategies are used following ochiectomy for stage one seminoma (SOS) of the testis. The aim of this systematic review (SR) is to provide evidence based guidelines for the follow-up (FU) schedule for each strategy regarding investigations required, frequency of assessment and overall duration. Methods: A SR of all prospective studies in SOS published since 1980 in MEDLINE, EMBASE and the Cochrane database was performed in November 2005. Data was extracted regarding the time, location and method of detection of first relapses, duration of FU, relapse free rates, and numbers of patients at risk. Five strategies were identified: Surveillance (S), Extended-field Radiotherapy (EFRT), Para-aortic Radiotherapy (PART) and either one (C1) or two (C2) cycles of Carboplatin chemotherapy. For each strategy Kaplan-Meier relapse free estimates were used to calculate weighted mean cumulative hazards of relapse over time. These were used to calculate yearly weighted mean relapse hazards. Weights used were based on numbers of patients at risk in each trial. Results: Fifteen prospective studies with a total of 5277 patients were identified. Actuarial relapse data was available in 4185 (79.3%) patients and 4850 (91.9%) had the location of relapse documented. Method of relapse detection was infrequently reported. The median time to relapse with all strategies was 12–16 months. Annual hazard ratios for relapse decreased with increasing length of FU and relapse location depended on the strategy used ( Table ). Conclusions: 1. The investigations performed need to reflect locations at risk of relapse. This should include computerised tomography (CT) of the abdomen and pelvis for Survillance and adjuvant Carboplatin, with CT of the pelvis only for Para-aortic RT. 2. Long term FU data on patients treated with Carboplatin is not available, and further FU is necessary. 3. Frequency of FU should reflect the annual hazard of relapse. We suggest 3 times per year when the risk is >5%, 2 times per year when the risk is 1–5%, and annually until the risk is <0.3%. [Table: see text] No significant financial relationships to disclose.
Salvage chemotherapy with high dose carboplatin + etoposide (HDCE) and peripheral blood stem cell transplant (PBSCT) in patients with germ cell tumors (GCT)
Authors: Einhorn L. H. , Williams S. , Abonour R. 
Published: March 2020

4549 Background: We began studies with HDCE for patients (pts.) with recurrent GCTs 20 years ago. During the past decade, better supportive care and use of PBSCT allowed outpatient therapy and more rapid hematopoietic recovery between the 2 courses of HDCE. Methods: Retrospective review of 184 consecutive pts. treated with HDCE at Indiana University from 2–96 to 12–04. Late relapse (> 2 years from prior therapy) and primary mediastinal non-seminomatous germ cell tumor pts. were not offered HDCE. Cytoreduction with 0–2 courses of vinblastine + ifosfamide + cisplatin preceded HDCE. C dosage was 700 mg/M2 × 3 and E 750 mg/M2 × 3. A second course was given after hematologic recovery. Results: Toxicity was as previously described (JCO 18:3346, 2000). There were 3 drug- related mortalities. An additional 3 patients developed AML (2 fatal), and 1 glioma following CNS XRT for metastases. 11 pts. did not receive second course (8 due to progression or HDCE mortality). Median time to second course HDCE was 28 days (range 20 to 42). 116 of 184 pts. are alive and continuously (cont) NED (63%) with median followup 42 months (range 11 to 118). 113 (97%) of these are 12+ months NED. 5 additional pts. are currently NED with further therapy. Results are tabulated below. Conclusions: HDCE has a high cure rate with acceptable toxicity as salvage therapy for GCT pts. [Table: see text] [Table: see text]
Predicting recurrence following post-chemotherapy retroperitoneal lymph node dissection for residual fibrosis or teratoma
Authors: Carver B. S. , Shayegan B. , Motzer R. J. , Bajorin D. , Kondagunta G. V. , Bosl G. J. , Sheinfeld J. 
Published: March 2020

4551 Background: The current recommendation for the management of patients with the histologic finding of fibrosis or teratoma at PC-RPLND is surveillance. We evaluated men at our institution who underwent PC-RPLND for metastatic non-seminomatous germ cell tumor (NSGCT) to determine predictors of disease recurrence. Methods: From 1989 through 2003, a total of 532 men underwent PC-RPLND for metastatic NSGCT at our institution. Of these, 473 (89%) had either fibrosis or teratoma present in the RPLND specimen. Following IRB approval, clinical and pathologic data were obtained from our prospective surgical database. A Cox regression model was constructed to evaluate variables that may predict for recurrence of viable NSGCT following PC-RPLND and a prognostic index was developed. Freedom from disease recurrence was analyzed using the Kaplan Meier method. Results: Of the 473 patients with fibrosis or teratoma, all patients underwent complete resection of all residual retroperitoneal masses, however 35 (7%) did not undergo a full PC-RPLND. With a median follow-up of 41 months, 47 (10%) patients relapsed with viable NSGCT. The 2- and 5- year probability of freedom from recurrent viable GCT for the entire cohort was 90% and 89%, respectively. In our multivariable model only post-chemotherapy nodal size > 5cm (p = 0.008), clinical stage III (p = 0.002), and absence of a full PC-RPLND (p = 0.002) were independent predictors for recurrence with viable NSGCT. Based on these three adverse predictors, a prognostic index was developed with favorable patients having no risk factors, intermediate prognosis patients with one risk factor, and poor prognosis patients having 2 or more risk factors. Favorable, intermediate, and poor prognosis patients had a 2-year progression free probability of 97% (95% CI 95–99%), 90% (95% CI 85–95%), and 66% (95% CI 54–78%), respectively (p < 0.001). Conclusions: This data suggests that patients who have a high risk of reucrrence with viable GCT should undergo more frequent follow-up during the first 2-years with serum tumor markers and imaging. Additionally, this data suggests that an incomlete RPLND is not sufficient surgery for men with metastatic NSGCT. These men should undergo a bilateral RPLND. No significant financial relationships to disclose.