bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I study of the VEGF receptor tyrosine kinase inhibitor vatalanib (PTK787/ZK 222584) and gemcitabine in patients with advanced pancreatic cancer
Authors: Kuo T. , Fitzgerald A. , Kaiser H. , Sikic B. I. , Fisher G. A. 
Published: March 2020

4122 Background: The VEGF pathway is the predominant mediator of angiogenesis in pancreatic cancer. Vatalanib (PTK787/ZK 222584) is a small molecule tyrosine kinase inhibitor of all known VEGF receptors. We initiated a phase I study of vatalanib and gemcitabine for advanced pancreatic cancer. Methods: Patients with newly diagnosed unresectable or metastatic pancreatic adenocarcinoma were enrolled. Previous adjuvant chemoradiotherapy with fluorouracil was allowed. Gemcitabine was given by fixed-dose rate infusion weekly x 3 in a 28-day cycle, and vatalanib was given orally daily. Dose-limiting toxicities (DLT) are defined as any grade 3/4 toxicity during the first cycle. The dose levels are as follows: Results: To date, 11 patients are evaluable for toxicity (5M/6F; median age 62 years, range 40–82 years; median KPS 90%). Thus far, 42 cycles have been given, with a median of four cycles per patient. Two patients have experienced DLT. The first patient (cohort 1) experienced grade 3 diarrhea and hypokalemia and grade 4 neutropenia occurring simultaneously and treated without sequelae. The second patient (cohort 3) developed grade 3 deep vein thrombosis. Beyond the first cycle, grade 3 toxicities included neutropenia (1), anemia (3), thrombocytopenia (1), hypertension (2), diarrhea (1), hypokalemia (1), thrombosis (1), and proteinuria (1). Three of eleven patients (27%) did not complete treatment to the first evaluation timepoint (2 cycles); two discontinued due to toxicity and one discontinued due to disease progression. Two of eleven patients (18%) had a partial response by RECIST. Six of eleven patients (55%) had stable disease as the best response ranging from 2–6 months. Conclusions: The combination of gemcitabine and vatalanib is generally well-tolerated with most grade 3/4 toxicities occurring late in the treatment course. Antitumor responses have been observed at initial dose levels and accrual to the final cohort with BID dosing of vatalanib continues. [Table: see text] No significant financial relationships to disclose.
Current status of targeted agents in advanced pancreatic cancer (APC): A pooled analysis of 2,361 patients (pts) enrolled in six phase III trials
Authors: Bria E. , Carlini P. , Gelibter A. , Ruggeri E. , Ceribelli A. , Pino M. , Terzoli E. , Cognetti F. , Giannarelli D. , Milella M. 
Published: March 2020

4126 Background: Molecular targeting of pathways that are deregulated in pancreatic cancer is a promising approach aimed at improving the dismal prognosis of APC pts. However, the clinical impact of novel “biological” drugs (ND) remains to be defined. Methods: All prospective phase III trials comparing single-agent Gemcitabine (G) with either a ND or a combination of ND and G (ND+G) were considered eligible. A pooled analysis was performed and event-based relative risk ratios (RR) with 95% CI were derived through both a fixed- and a random-effect model approach, exploring OS as the primary outcome and PFS and ORR as secondary outcomes. Heterogeneity between different trials was also taken into account. Results: Six trials involving 2361 pts were identified; ND tested included: FTI inhibitors (1 trial), MMP inhibitors (3 trials), EGFR inhibitors (1 trial), and anti-gastrin vaccine (1 trial). The analysis was conducted considering three different subgroups: 1) overall population (2361 patients, 6 trials), 2) ND+G vs G (1879 patients, 4 trials), and 3) ND vs G (482 patients, 2 trials). As shown in the table, no significant differences in either the primary outcome (OS) or the secondary outcome of PFS were observed in the overall population as well as in ND+G vs G trials, while a significant negative trend for ND was found in ND vs G trials with regard to both endpoints. Conversely the evaluation of the secondary endpoint of ORR significantly favored G in the overall population as well as in ND vs G trials, while a not significant negative trend for ND was observed in ND+G vs G trials. Conclusions: G remains the treatment of choice in APC pts. The ND tested, either alone or combined with G, do not seem to add any benefit over G. A better understanding of pancreatic cancer biology and further clinical evaluation of new agents and is needed to improve prognosis in APC pts. [Table: see text] No significant financial relationships to disclose.
Improvement of survival in VA patients with gall bladder cancer given chemotherapy
Authors: Atiq M. , Safa M. M. , Komrokji R. S. , Jazieh A. R. , Muhleman A. F. , Nahleh Z. A. , Pancoast J. 
Published: March 2020

4132 Background: Gallbladder carcinoma, though rare, has very poor prognosis. Most of patients with gall bladder carcinoma present with either unresectable disease or metastasis. Median survival in gall bladder carcinoma has been documented to be 6 months in SEER data. There is no data available on the outcome of Veterans’ Affair (VA) patients with gall bladder carcinoma. Impact of chemotherapy in adjuvant and metastatic setting is not well-studied. Methods: We used the VA Central Cancer Registry (VACCR) to analyze VA patients with Gall Bladder cancer diagnosed between 1995 and 2005. The reference date for data collection and reporting is January 1, 1995. This site aggregates the data collected by the medical centers’ cancer registries. Data was entered and analyzed using bio-statistical software SPSS. Results: There were a total of 232 patients. Of these, 185 (79.7%) were whites and 37 (15.9%) were blacks. The mean age was 71 years. Pathology was adenocarcinoma in 198 (85.3%), non-specified carcinoma in 29 (12.5%) and small cell carcinoma in 5 (2.2%) cases. Overall median survival was 5.27 months. Surgery was performed in 119 patients (51%). Only 19 (16%) patients received adjuvant chemotherapy. The baseline characteristics were similar between patients who received adjuvant chemotherapy and no adjuvant chemotherapy. Also, the median survival was similar (8.3 months vs. 8.7 months) (P-value 0.37). In patients who did not undergo surgery, the median survival for patients who received chemotherapy was 8.0 months vs 1.7 months for patients who did not receive chemotherapy (p-value 0.013). Eighty-nine (38.5%) patients were diagnosed with stage IV disease. Amongst these patients chemotherapy improved the median survival (2 months vs. 6.97 months; p-value 0.04). In a Cox regression model stage, surgical margins, surgery, chemotherapy were independent predictors of patient survival. Conclusions: Gall bladder carcinoma in VA patients has similar survival compared to other reports. Our data is one of the largest retrospective cohorts in gall bladder cancer and suggests that chemotherapy improves survival in advanced gall bladder cancer patients. No significant financial relationships to disclose.
SWOG S0202: A phase II trial of gemcitabine and capecitabine in patients (pts) with unresectable or metastatic gallbladder cancer or cholangiocarcinoma
Authors: Iqbal S. , McCoy S. , Lenz H. J. , Rivkin S. E. , Atkins J. N. , Blanke C. D. 
Published: March 2020

4134 Background: Pts with gallbladder cancer or cholangiocarcinoma usually present with advanced disease and limited treatment options. Based on data demonstrating effectiveness of gemcitabine in pancreatic carcinoma and the common embryologic origin of the exocrine pancreas and gallbladder, this trial was pursued. The primary objective of this study was to assess the response rate (confirmed complete and partial responses). Secondary objectives included overall survival and toxicities for gemcitabine and capecitabine. Methods: A two-stage design was used to detect a difference in the null hypothesis of 5% response probability and the alternative 20% response probability. If at least one response occurred after the first 20 pts, another 20 were to be accrued. The combination of gemcitabine 1,000 mg/m2 IV over 100 minutes days 1, 8 and capecitabine 650 mg/m2 BID PO days 1–14, was administered every 21 days. Results: The study accrued 57 pts from September 2003 until April 2005. Three patients were ineligible, and two others received no treatment. Characteristics of analyzable pts: 35 (73%) cholangiocarcinoma, 17 (32%) gallbladder cancer; PS 0 (18 pts), 1 (26 pts), 2 (8 pts); 26 (50%) male; median age 58.8 years (29.5–85.6). Among 51 pts evaluated for toxicity, 6 experienced grade 4 toxicities: 1 thrombosis/embolism and muscle pain, 1 fatigue and 4 neutropenia, one of whom also had grade 4 leukopenia and grade 4 anemia. Among 52 pts, there were 5 confirmed partial responses for a confirmed response probability of 10% (95% CI 3% to 21%). Four pts had an unconfirmed partial response for an overall response probability of 18% (95% CI 8% to 30%). Fourteen patients (27%) stable disease. The 6 month overall survival was 56% (95% CI 42%–70%) and median survival was 7.0 months. Conclusions: Gemcitabine and capecitabine is a well tolerated regimen with activity in pts with advanced gallbladder cancer and cholangiocarcinoma. Correlative analyses are ongoing. [Table: see text]
Correlation of Ki67, topo IIa, MRP1, p53 and p-gp with chemo-responsiveness and survival in patients with hepatocellular carcinoma (HCC)
Authors: Yeo W. , Wong W. L. , Wong N. , To K. F. , Mo F. K. , Chan A. T. , Lai P. B. , Koh J. , Johnson P. J. 
Published: March 2020

4139 Background: HCC is a common cause of cancer morbidity and mortality. For patients (pts) who are not candidate of curative surgery, chemotherapy (CT) is one of the main treatments but response has been poor due to drug resistance. In this study, using the pre-CT tumor biopsies of HCC pts who were entered into our recently reported phase III prospective randomized CT study (J Natl Cancer Inst 2005; 97(7): 536–539), we aimed to correlate selected biomarkers with CT responsiveness and survival. Methods: 188 HCC pts were entered into the CT study. They were separately consented for the present correlative study. CT response was based on WHO criteria. For the purpose of this study, pts were categorized into CT-‘responsive’ group (those who obtained clinical benefits and achieved CR, PR or SD) and CT-‘non-responsive’ group (those who developed PD). Immunohistochemical staining for Ki67, topo IIa, MRP1, p53 and p-gp were performed on the pre-CT tumor biopsies; findings of which were analyzed with conventional clinical variables to identify factors that influenced CT response and survival. Results: 149 pts had pre-CT tumor biopsies available and were thus included in the present analysis, 1 pt was not assessable for response; there were 75 pts in the CT-‘responsive’ group (23 PR and 52 SD) and 73 pts in the CT-‘non-responsive’ group. The overall median survival was 7.9 months. Using multivariate analysis, predictors of response to CT were Ki67 positivity (p = 0.0427; OR = 0.475), MRP1 positivity (p = 0.0323; OR = 0.429), age (p = 0.0027; OR = 1.056) and albumin level (p = 0.0130; OR = 1.108). Predictors of survival included Ki67 positivity (p = 0.0097; HR = 1.662), topo IIa positivity (p = 0.0358; HR = 1.566), total bilirubilin level (p = 0.0006; HR = 1.039) and ALT level (p = 0.0092; HR = 1.005). Conclusions: In addition to conventional factors, Ki67 and MRP1 positivity are predictors of response to CT, while Ki67 and topo IIa positivity are predictors of survival. The present study demonstrates that immunohistochemical staining of biomarkers can be instrumental in highlighting genes in the drug-resistant phenomenon of HCC. Acknowledgements: This study has been supported by the Direct Grant of Chinese University of Hong Kong, project no. 2041124. No significant financial relationships to disclose.
Pemetrexed (A)/platinum for patients with advanced malignant peritoneal mesothelioma (AbM)—The Bielefeld experience
Authors: Karthaus M. , Frieler F. , Vasquez N. , Grader K. , Pfeil N. , Plahl A. , Tagizadeh K. , Trapp M. , Metzner D. 
Published: March 2020

4151 Background: AbM is a very rare and aggressive neoplasm of the peritoneum. Treatment data of AbM are commonly case reports. A is approved for pleural mesothelioma (MPM) with rare data however regarding AbM. Methods: We evaluated efficacy and safety data of A (500 mg/m2) +DDP (75 mg/m2) or carboplatin (AUC 5) in AbM prospectively. Ctx was given d1 and repeated on d22 for 6 cycles or disease progression. Folic acid 400 μg po/d and vitamin B12 1000 μg i.m. qw 9 wks was administered to prevent AE . Study endpoints were best response (CR/PR), time to progression (TTP), survival and safety. Results: 89 consecutive mesothelioma pts were observed from 12/2002 until 12/2005 in a German single center institution. Four pts (1 AbM, 1 MPM, 2 MPM+AbM) were excluded due to renal impairment (n = 1) or death prior to Ctx (n = 3). AbM was diagnosed in 22 pts (16 epitholoid, 1 sarcomatoid, 5 other), while 5 additional pts had mesothelioma on both sites of the diaphragma. Efficacy data are available in 19 pts with AbM and 5 pts with AbM + MPM. Initial combination was with DDP in 21 pts treated with AbM. DDP was given in 3 and carboplatin combination in 2 pts with MPM + AbM. A was administered a median of 6 cycles in AbM (range 1–33). Toxicity (WHO > III/IV) was nausea (n = 4) and neutropenia (n = 4). Up to 12/05 death has been reported in 8 out of 22 pts with AbM, and in 3 of 5 pts with AbM + MPM. Mean survival was 13,65 months (range 1 to 35+ months) in AbM. Benefit for AbM was 77% with objective RR in 36%. Mean TTP was 11,54 months (range 0 to 35+) in AbM vs 15,4 months with MPM + AbM with a mean survival of 13,65 months (range 0 to 35+) and 22,3 months (range 0 to 35+) in the latter group. Conclusions: Pemetrexed with platinum is well tolerated and has substantial activity for malignant peritoneal mesothelioma. Further trials are warranted to prove this hopeful concept of pemetrexed based therapy for advanced AbM. [Table: see text] No significant financial relationships to disclose.
A retrospective review of anal squamous cell carcinoma in HIV positive and HIV negative patients
Authors: Grandhi J. , Philip P. A. , Washington T. , Shields A. F. , Vaishampayan U. , Heilburn L. K. , Venkatramanamoorthy R. , El-Rayes B. F. 
Published: March 2020

4153 Background: The incidence of invasive anal cancer is 120 times higher in the HIV infected patients than in the general population. The outcome of anal cancer in HIV infected patients has not been evaluated in prospective trials and the published literature is limited to small retrospective case series. The aim of this study is to describe the outcome, tolerability, event free survival, and overall survival in patients with squamous cell carcinoma of anal canal (SCCAC) with and without HIV infection treated at Karmanos Cancer Institute/Wayne State University from 1991 to 2005. Methods: We performed a retrospective chart review. Patients were identified using the SEER database. We collected data regarding HIV status, demographics (age, gender, race), stage at diagnosis, treatment, response to treatment, toxicity and survival. Results: Forty patients with SCCAC were identified, of which 13 were HIV positive and 27 were HIV negative. The HIV-positive and HIV-negative groups differed by mean age (44 vs. 55 years), male gender (100 vs. 37 percent), and African American race (92 vs. 59 percent). There were no differences in stage at diagnosis, type of chemotherapy received. HIV positive population received reduced chemotherapy (67 vs. 8 percent), and RT (22 vs. 7 percent) dosage. The major toxicities observed in HIV positive and negative patients were mucositis (23% vs. 29%), neutropenia (8% vs. 33%) and skin toxicity (46% vs. 55%) secondary to radiotherapy. Only 61 percent of HIV-positive patients were disease free vs. 60 percent of HIV-negative patients. Conclusions: We found that HIV positive patients received lower doses of chemo-radiotherapy. Patients with HIV tolerated the lower dose chemoradiotherapy and had a similar toxicity profile to the HIV negative patients. No major difference in the risk of recurrence between HIV positive and negative patients was observed. No significant financial relationships to disclose.
Annual zoledronic acid to prevent gonadotropin-releasing hormone agonist-induced bone loss in men with prostate cancer: A randomized placebo-controlled trial
Authors: Michaelson M. D. , Lee H. , Kaufman D. S. , Kantoff P. W. , Finkelstein J. , Smith M. R. 
Published: March 2020

4515 Background: Gonadotropin-releasing hormone (GnRH) agonists decrease bone mineral density (BMD) and increase fracture risk in men with prostate cancer. Zoledronic acid (4 mg IV every 3 months) increases BMD in GnRH agonist treated men. Intermittent zoledronic acid (4 mg IV once annually) increases BMD in postmenopausal women with osteoporosis but the efficacy of the annual treatment schedule in hypogonadal men is unknown. Methods: In a 12-month open-label study, men with nonmetastatic prostate cancer (n = 44) who were receiving a GnRH agonist were assigned randomly to zoledronic acid (4 mg IV × 1) or placebo. BMD of the posteroanterior lumbar spine and total hip were measured by dual energy x-ray absorptiometry at baseline and month 12. Serum N-telopeptide, a marker of osteoclast activity, was measured every 3 months. Results: Mean (± SE) BMD of the posteroanterior lumbar spine increased by 4.0 ± 0.9 in men treated with zoledronic acid and decreased by 3.1 ± 0.9 percent in men who received placebo (P < 0.001 for between-group comparison). BMD of the total hip decreased by 0.7 ± 0.6 percent in men treated with zoledronic acid and decreased by 1.9 ± 0.7 percent in men who received placebo (P = 0.005). Compared to placebo, zoledronic acid significantly decreased serum N-telopeptide throughout the 12-month study (P < 0.05). Conclusions: In men receiving a GnRH agonist for prostate cancer, a single treatment of zoledronic acid significantly increased bone mineral density of the total hip and spine at 12 months. Annual zoledronic acid may provide a convenient and effective strategy to prevent bone loss in hypogonadal men. This study was supported in part by Novartis Oncology and by the Prostate Cancer Foundation. [Table: see text]
Association of pain and quality of life (QOL) response with PSA response and survival of patients (pts) with metastatic hormone refractory prostate cancer (mHRPC) treated with docetaxel or mitoxantrone in the TAX-327 study
Authors: Berthold D. R. , Pond G. , De Wit R. , Eisenberger M. A. , Tannock I. F. 
Published: March 2020

4516 Background: The TAX-327 study compared 3 weekly docetaxel (D3), weekly docetaxel (D1) or mitoxantrone (M), each with prednisone (P) for 1006 pts with mHRPC. Survival and symptom control were superior following D3+P as compared to M+P (Tannock et al, NEJM 2004;351;1502–12). Here we investigate associations between pain and QOL response with PSA response and survival. Methods: Pts were evaluated for pain, PSA and QOL at baseline and 3 weekly during treatment. Pain response (pts with initial pain) was defined by ≥ 2-point reduction in Present Pain Intensity (PPI) with no increase in analgesic score (AS) or ≥ 50% in AS with no increase in PPI. PSA response required ≥ 50% reduction in PSA from baseline. QOL response required ≥ 16-point reduction in FACT-P score (range: 0–156). Responses were confirmed ≥ 3 weeks later. Results: There were414 pts assessable for both pain and PSA response: PSA response was seen in 52.4% of 124 pts with pain response and 28.3% of 290 pts without pain response (p < 0.001). There were 704 pts evaluable for both QOL and PSA response: PSA response occurred in 56.5% of 147 pts with QOL response and 37.5% of 557 pts without QOL response (p < 0.001). The table shows associations of pain or QOL response and survival. Landmark analysis will be presented at the meeting. After adjustment for PSA and QOL response, pain response was an independent predictor of survival (HR = 0.47, p = 0.003). Conclusions: Pain and QOL response were associated with PSA response and pain response was an independent predictor of survival. [Table: see text] [Table: see text]
Prognostic factors for relapse in stage I seminoma managed by surveillance or adjuvant carboplatin: A multivariate analysis on 588 cases
Authors: Aparicio J. , Garcia-Puche J. , Lomas M. , Carabantes F. , Vazquez S. , Crespo C. , Climent M. , Murias A. , Oltra A. , Barrajon E. 
Published: March 2020

4552 Background: The availability of reliable prognostic factors for relapse in stage I seminoma would allow a better patient stratification for individually tailored therapies. We performed a pooled analysis of patients included in two consecutive risk-adapted protocols. Methods: Between 1994 and 2004, 588 cases were prospectively registered. Median patient age was 33 years, median tumor size was 45 mm, serum BHCG levels were elevated preoperatively in 14.6%, and rete testis invasion was present in 26.9%. Three hundred and four patients (51.7%) with risk factors received two courses of adjuvant carboplatin, whereas 284 (48.3%) without these criteria were managed by surveillance. After a median follow-up of 48 months (range, 12–144), 43 relapses (7.3%) have occurred. Five-year disease-free survival was 92.3%. Univariate (log rank) and multivariate (Cox regression) analyses of prognostic factors for relapse were performed. Results: Relapses were less frequent after carboplatin treatment (3% vs 12%, p < 0.0001). Statistically significant, independent predictors of relapse were: 1) rete testis invasion and age (<30 years) in the whole series; 2) rete testis invasion for patients treated with adjuvant chemotherapy; and 3) tumor invasion beyond the albuginea and microvessel neoplastic invasion (defining 1997 AJCC pT2–4 staging) for patients managed by surveillance. In contrast, tumor size, histologic subtype (anaplastic), and serum preoperative BHCG levels were not associated with prognosis. Conclusions: Invasion of the rete testis and age (<30 years) represent high-risk factors for patients with clinical stage I testis seminoma, independently of the treatment selected. These two features, in combination with pathologic T2–4 staging, could improve patient selection for risk-adapted therapies. No significant financial relationships to disclose.