bluuebunny/crossref_metadata_2025_split huggingface dataset:
A phase I/II study of telomerase peptide vaccination in combination with chemotherapy in patients with stage IV malignant melanoma
Authors: Aamdal S. , Dueland S. , Engebraaten O. , Owre K. , Dyrhaug M. , Trachsel S. , Gaudernack G. 
Published: April 2020

8031 Background: A phase I/II feasibility study was conducted to investigate the safety, tolerability and immunological response to vaccination with the telomerase peptide GV1001 (hTERT: 611–626) in combination with temozolomide (T). Methods: Twenty-five patients with malignant melanoma (15 stage M1c,10 stage M1b) received T day 1–5 every four weeks for 1–9 cycles. During the first cycle (4 weeks) they received i.d. injections of 560 μg GV1001 with local GM-CSF in week 2,3 and 4, followed by injections in week 6 and 7 in the second cycle and week 11 in the third cycle. The treatment period was 12 weeks (3 cycles). Booster vaccinations with 560 μg GV1001 were offered every third month. Monitoring of blood samples, clinical examination were performed regularly with radiological staging every 12th week. Immune responses were measured as DTH and in vitro T-cell proliferation. Results: The treatment was generally well tolerated with only grade 1–2 toxicity in most patients. Of 14 patients, 4 developed grade 3 toxicity and one grade 4 toxicity (neutropenia). Immune responses against GV1001 were detected in 17/21 patients (81%) at 12 weeks. Patients receiving up to 9 cycles of T exhibited stable proliferative responses to GV1001 throughout the treatment period. None of the patients had DTH response at trial entry and no DTH responses were observed in patients receiving T. This was not due to a shift in the cytokine profile since cloned GV1001-specific CD4+ T cells displayed a Th1 cytokine profile. Upon evaluation in week 12, 6 patients had SD, 10 PD. One patient had a PR with shrinkage or disappearance of multiple lung metastases. A patient continuing on vaccine alone developed significant DTH response when T therapy was stopped. Conclusions: Telomerase vaccination of patients receiving concomitant T treatment is feasible. The unexpected high proportion of patients showing an immune response indicates that regulatory T-cells may have been removed by T treatment. The chemotherapy may also have influenced effector cells required for development of skin reactions. In spite of lacking DTH response however, the majority of the patients demonstrated significant immune response indicating different regulation of DTH and T-cell response. No significant financial relationships to disclose.
Randomized phase II study of low (100mg) versus intermediate (400mg) doses of thalidomide (Thal) plus DTIC in metastatic melanoma (MM)
Authors: Von Moos R. , Dummer R. , Inauen R. , Ruhstaller T. , Meier S. , Skalsky J. , Hitz F. , Korte W. , Cerny T. , Gillessen S. 
Published: April 2020

8048 Background: Single agent DTIC is the standard therapy for MM. In an effort to improve the response rate (DTIC 7–13%), Thal, a molecule with antiangiogenic effect was added in two different dosages to DTIC. Methods: Eligibility: Stage IV MM, ECOG performance status 0–2, no prior treatment with DTIC or Thal. Design: Randomized multicenter phase II Bryant and Day 2-stage optimal design with 20 patients (pats) per arm. Treatment regimens: DTIC 200mg/m2 d1–5 q3w plus Thal (100 versus 400mg per day). Responses were assessed every two cycles. Endpoints: Toxicity, feasibility, response rate (RR) and time to treatment failure (TTF). Results: 26 pats (12 male/ 14 female) at a median age of 58 years (range 24–82) with stage IV melanoma (M1a-2, M1b-2, M1c-22) were enrolled between 2001–2005 and received a median of 4 cycles (1–6). All the pats were evaluated for toxicity, 25 (96%) were assessable for objective response (WHO criteria). The overall response rate of the evaluable patients was 27% (100mg, RR 25%; 400mg, RR 33%), one patient (4%) had a complete response, 6 pats (23%) had a partial response, 11 pats had stable disease (42%), and 7 pats (27%) progressed. The median TTF was 5.2 months. Using NCI 2.0 Common Toxicity Criteria, grade 3 haematological toxicity was 12% (anemia-1, leucopenia-1, thrombocytopenia-1). Cumulative non-haematological toxicity grade 3/4 was 35% including fatigue in 5 pats (all on 400mg Thal arm), thromboembolic events in 2 (1 each treatment arm) and bleeding in 2 (1 cerebral). Polyneuropathy and constipation were a minor problem (no grade 3/4). The 400mg Thal arm was stopped according to the protocol because of intolerable fatigue in 5 out of 6 patients. Two of the first 14 pats suffered from pulmonary embolism. Thromboprophylaxis with low molecular weight heparin (LMWH) was mandatory after an amendment . Thereafter no thromboembolic events were seen but one fatal cerebral bleeding occurred in one patient. Conclusions: 400mg Thal in combination with DTIC was not feasible due to toxicity. 100mg Thal was well tolerated and showed significant clinical activity. Using our low dose Thal regimen prophylactic LMWH is necessary to prevent severe thromboembolic events. No significant financial relationships to disclose.
Effects of depression on quality of life in Medicare beneficiaries with prostate cancer
Authors: Chang C. , Knight S. J. , Bennett C. L. 
Published: April 2020

8510 Background: Depression is very common in the elderly and is particularly costly because of associated mortality, excess disability, and interactions with other physical health problems. We aimed to examine the impact of depression on quality of life in the older prostate cancer patients receiving Medicare benefits. Methods: Data came from the 2003 Cohort VI Baseline Medicare Health Outcomes Survey. Among the 109,115 individuals, only those who were under treatment for prostate cancer and completed the survey themselves were included in this study (n=2,191). Quality of life was assessed using the SF-36 questionnaire and the physical and mental health component scores (higher scores indicating better health) were analyzed. Results: Eighty-eight percent were whites, 75% were married, 76% had at least high school education, 45% were aged 65 to 74, and 55% were aged 75 and older. Those who reported having been depressed in the past two weeks (n=453; 21%) had significantly lower physical health (34.06 vs. 40.24; p < .001) and mental health (41.14 vs. 54.41; p < .001) than those who did not. Similar patterns were observed for those who endorsed questions indicating “depression much of the time in the past year” and “depression most of the time in the past 2 years”. Conclusions: Depression is prevalent among older men diagnosed with prostate cancer, and those who acknowledge being depressed in the past 2 weeks to 2 years have significantly worse mental and physical health. Attention to depression, in addition to prostate cancer specific issues, should be considered among prostate cancer patients who report mental or physical health problems. Early detection and treatment of depression in this population could potentially alleviate their suffering and improve their quality of life. No significant financial relationships to disclose.
Patients’ characteristics and outcomes of palliative care inpatient consults at a comprehensive cancer center
Authors: El Osta B. , Braiteh F. S. , Reddy S. , El Osta H. , Bruera E. 
Published: April 2020

8524 Background: There is limited information about the characteristics and outcomes of inpatient palliative care consults in cancer centers. Two mobile teams (MT) each with a physician, fellow, and a nurse, provide consultation to hospitalized patients (pts) with complex symptoms. Methods: We analyzed the pts characteristics and outcomes during a two-month period. The charts were reviewed for demographics, cancer data, reason for consultation, symptoms, interventions, and outcomes. Results: Sixty-one pts were analyzed. Pain was the main reason for a consult request in 46 pts (75%), delirium in 10 (16%), anxiety in 4 (7%) and constipation in 5 (8 %). Some pts had more than one reason. 56(92%) pts had metastatic disease, diagnosis for ≤1 year in 26 (42%) and ≤2 years in 44 (72%) (Median =17 months). The Edmonton Symptom Assessment Scale (ESAS), 0–10, is summarized in the table. We uncovered new issues at consultation, such as 20 pts (38%) screened positive for alcoholism with CAGE questionnaire and the 34 pts (56%) had clinical delirium. Features of opioids toxicity such as constipation (N=43;70%), confusion (N=35;57%) (Mean MMSE = 23 ± 5), hallucinations (N=21;34%), myoclonus (N=16;26%) and miosis (N=18;29%) were frequently identified. The MT interventions included imaging studies (23%), enema (43%), laxatives (49%), neuroleptics (54%), metoclopramide (39%), corticosteroids (25%). Half (N=30;50%) of the pts had opioid rotation and/or had counseling (N=27;46%). One out of two pts (N=30;49%) required transfer to the palliative care unit. Conclusions: Most pts had previously undiagnosed opioid toxicity, delirium, and other symptoms. Opioid toxicity occurred secondary to rapid opioid escalation, possibly linked to chemical coping, and psychosocial distress. The outcome of these pts improved by opioid rotation, adding laxatives, metoclopramide, neuroleptics, and steroids. [Table: see text] No significant financial relationships to disclose.
Effect of the number of bone lesions on efficacy of zoledronic acid for prevention of skeletal-related events (SREs) in patients with bone metastases from solid tumors
Authors: Shirina N. , Coleman R. E. , Chen Y. M. 
Published: April 2020

8529 Background: It has been postulated that greater numbers of bone metastases and thus greater tumor burden may lead to increased skeletal morbidity. To assess the effect that the number of baseline bone metastases may have on the efficacy of zoledronic acid in patients with solid tumors, we conducted a retrospective analysis of 3 large, randomized, controlled trials. Methods: Data were evaluated from the intent-to-treat population with breast cancer (n = 739), prostate cancer (n = 397), or lung cancer and other solid tumors (n = 480) who were treated with zoledronic acid 4 mg, pamidronate 90 mg, or placebo and had information available on number of baseline bone lesions. Patients were stratified into 2 groups: those with ≤ 3 bone lesions or > 3 lesions. Results: In general, patients with > 3 lesions had a higher skeletal morbidity rate (SMR) compared with patients with ≤ 3 lesions (Table 1), and zoledronic acid reduced SREs regardless of the number of bone lesions, but the benefit of zoledronic acid appeared greater in patients with > 3 lesions. In patients with lung cancer and other solid tumors who had > 3 bone lesions, zoledronic acid significantly reduced the mean SMR (P = .008) and significantly prolonged time to first SRE (median, 171 vs 84 day; P = .005) compared with placebo. In prostate cancer patients with > 3 bone lesions, zoledronic acid also significantly reduced the mean SMR compared with placebo (Table 1). In breast cancer patients with > 3 bone lesions, the mean SMRs were similar for zoledronic acid and pamidronate groups (Table 1). Conclusions: Patients with a greater number of bone lesions are at higher risk for skeletal complications and receive greater clinical benefit from treatment with zoledronic acid. [Table: see text] [Table: see text]
Activity limitation and clustering of symptoms in breast cancer patients
Authors: Sawhney R. , Sehl M. E. , Sanati H. , Satariano W. A. , Naeim A. 
Published: April 2020

8540 Background: While previous cancer symptom research has been focused on individual symptoms, more recent studies have attempted to identify symptom clusters in breast cancer patients. However, there has been no large study that has examined both clustering of symptoms and activity limitation in breast cancer patients. Methods: Data were taken from a survey study of 1,011 patients found to have histologically confirmed breast cancer, identified by the Metropolitan Detroit Cancer Surveillance System. Patients were surveyed at both 3 and 12 months after diagnosis. Survey data on 1,054 control participants were also obtained for matching variables. Participants were asked whether or not they had each of 21 symptoms, and whether or not they attributed any activity limitation to each symptom. Results: Of 21 symptoms examined, prevalence of symptoms listed in Table 1 was significantly higher in cancer patients than in controls (p<0.05) at baseline. Though the prevalence of each symptom decreased significantly at follow up, each symptom remained significantly more prevalent than in the control group, with the exception of depression. Activity limitation attributed to 4 of the 5 symptoms listed in Table 1 was significantly higher than that of controls, and this difference persisted at follow up. Symptoms tended to cluster together amongst breast cancer patients. For example, at baseline, 73% of patients with depression also reported fatigue, and 30% of patients with pains in chest area also reported both fatigue and depression. These associations persisted at follow up. Symptoms were significantly correlated with each other at baseline (p<0.00005), with correlation coefficients ranging from 0.13 to 0.26, with most correlations remaining significant at follow up. Conclusion: In a large survey of breast cancer patients, symptoms were found to be associated with significant activity limitation, and tended to cluster together. This correlation persists at 12 months after diagnosis, even after treatment is complete. [Table: see text] No significant financial relationships to disclose.
Comorbidity and choice of adjuvant endocrine therapy in breast cancer patients (pts) older than 70 years
Authors: Monfardini S. , Brunello A. , Molino A. , Sacco C. , Simoncini E. , Gasparini G. , Bella M. A. , Crivellari D. , Vamvakas L. , Basso U. 
Published: April 2020

8546 Background: Tamoxifen (Tam) and aromatase inhibitors (AI) have different profiles of toxicity which may influence the therapeutic choice in the presence of associated diseases, but few data are available concerning the prevalence of such comorbidities. Methods: A retrospective analysis on 434 consecutive pts (≥70 years) radically operated for breast cancer was conducted in 26 italian centers to determine how comorbidity influenced the choice of endocrine therapy during the year 2004. Results: Out of 434 pts, 367 with estrogen receptor positivity (median age 75, range 70–93) were treated with endocrine therapy alone (330 pts) or combined with chemotherapy (37 pts). The mean number of comorbidities was 1.8; 99 pts (26.2%) had ≥3 associated diseases. Tam was given to 194 pts (52,8%), AI to 173 pts (47,2%): Anastrozole (149 pts) Letrozole (22 pts) or Exemestane (2 pts). In 126/367 pts (34%) AI were prescribed instead of Tam because of the contraindications listed in the table below. AI were the preferred choice in 46/367 (12,5 %) pts in the absence of contraindications to Tam. Whereas the prevalence of osteoporosis is more than 30% in women after 70 years in Italy, a reduction of bone density had been instrumentally documented only in 10 pts (2.7%) of this survey, and AI were prescribed in 6 of them. Conclusions: Tam was still the preferred option in elderly women with early breast cancer, but was contraindicated in more than one third of pts. These data suggest that osteoporosis is being probably underdiagnosed in patients over 70 years. In view of a possible treatment with bisphosphonates, screening bone mineralometry should become standard before starting therapy with AI. [Table: see text] No significant financial relationships to disclose.
Randomized pharmacokinetic evaluation of subcutaneous versus intravenous administration of granisetron in cancer patients treated with platinum-based chemotherapy
Authors: Perez-Gracia J. , Sadaba B. , Lopez-Picazo J. , Azanza Perea J. , Cabello J. , Campanero Martinez M. , Martin Algarra S. , Gil-Aldea I. , Garcia-Foncillas J. , Gurpide A. 
Published: April 2020

8557 Background: 5-HT3 antagonists are one of the mainstays of antiemetic treatment and they can be used either intravenously or orally. Nevertheless sometimes neither intravenous (IV) nor oral administration is possible, such as in patients unable to admit oral intake managed in an outpatient setting. Our objective was to assess if pharmacokinetics of subcutaneous (SC) granisetron were comparable to IV delivery, using Area Under the Curve between 0 and 12 hours (AUC 0–12 h) as our main endpoint. Methods: Patients receiving platinum-based chemotherapy were randomized to receive granisetron 3 mg by either SC or IV administration during the first cycle and by the other route during the second one. Blood samples were drawn at 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8 and 12 hours after granisetron. Drug levels were determined by HPLC with fluorescence detection after liquid-liquid extraction of the samples, with a quantitation limit of 1 ng/ml. Clinical assessment of emesis in both cycles was performed. Results were analyzed using Student’s t-test and Wilcoxon test for paired samples. Assuming a 20% difference in AUC 0–12 h between both routes, 25 patients were required to obtain statistical significance (α=0.05, β=0.10). The protocol was approved by the Ethics Committee and all patients signed informed consent. Results: From May to November 2005, 30 patients were included and 25 of them were evaluable. SC granisetron resulted in a 27% increase in AUC 0–12 h (95% CI: 7–74) and higher levels at 12 hours (see table). Cmax was higher and was reached faster by IV route. Emetic symptoms were equivalent with both alternatives. Conclusion: SC administration of granisetron achieves higher AUC 0–12 h than IV administration, resulting in increased exposition to the drug. This is the first study that shows that SC granisetron is a valid alternative to IV or oral use. This new route of administration might be specially relevant for outpatient management of emesis in cancer patients. [Table: see text] No significant financial relationships to disclose.
Effects of adjuvant chemotherapy on the protein C anticoagulant pathway in patients with early stage breast cancer
Authors: Mukherjee S. D. , Levine M. , Beaudin S. , Shin L. , Caruso S. , Liaw P. 
Published: April 2020

8563 Background: Although chemotherapy treatment is associated with an increased risk of thrombosis, the pathogenic mechanisms are poorly understood. We have previously shown that treatment of endothelial cells with adriamycin and epirubicin impairs the protein C anticoagulant pathway by downregulating EPCR (endothelial protein C receptor), an endothelial receptor required for the conversion of protein C to the anticoagulant enzyme activated protein C (APC). In this study, we examined the effects of adriamycin- and epirubicin-containing chemotherapy on the protein C anticoagulant pathway in early stage breast cancer patients. Methods: We collected blood samples from 20 patients patients with early stage breast cancer undergoing adjuvant CEF (cyclophosphamide, epirubicin and 5-fluorouracil) or CMF (cyclophosphamide, methotrexate and 5-fluorouracil) chemotherapy on days 1, 2 and 8 for the first 2 cycles of treatment. Markers of protein C generation (protein C, thrombin-antithrombin (TAT) complexes, and APC) were measured on these days. Results: Plasma protein C levels were significantly lower at cycle 2 day 8 (0.88 ± 0.14 U/ml) compared to pre-chemotherapy levels (1.07 ± 0.23 U/ml) (p=0.0036). Plasma TAT levels were significantly higher at cycle 2 day 8 (2.87 ± 0.79 μg/L) compared to pre-chemotherapy levels (2.01 ± 1.24 μg/L) (p=0.02). Based on the APC levels, the patients appear to fall into two categories in terms of their ability to generate APC. The first group (n=16) has elevated APC levels that parallel the elevated TAT levels, whereas the second group (n=4) has low APC levels despite elevated TAT levels. Conclusions: Impaired ability to generate APC in a subpopulation of patients may reflect chemotherapy-induced impairment of the protein C pathway through the downregulation of EPCR. This pilot study provides new mechanistic insights into the prothrombotic effects of chemotherapy agents. No significant financial relationships to disclose.
Prevalence of anemia in cancer patients not receiving antineoplastic treatment (ANT): Data from the European Cancer Anaemia Survey (ECAS)
Authors: Gascon P. , Barrett-Lee P. J. 
Published: April 2020

8565 Background: Cancer-associated anemia occurs frequently in patients receiving ANT. Patients not receiving ANT may also have low hemoglobin (Hb) levels that may compromise optimal disease management and patient outcomes. Methods: Patients enrolled in ECAS (Ludwig et al, Eur J Cancer 2004;40:2293–2306) and not receiving ANT (chemotherapy, radiotherapy, or hormonal treatment) at enrollment were evaluated for prevalence of anemia (Hb <12.0 g/dL), effect of anemia on performance according to WHO score (0 to 4), and anemia treatment. Disease status at enrollment was catagorized as newly diagnosed (ND), persistent/recurrent (P/R), or in remission. Results: Of 15,367 enrolled patients, 7947 (53%) were not receiving ANT: 60% ND; 28% P/R disease; 12% in remission. Anemia was present in 32% of patients, with Hb levels 10.0–11.9 g/dL in 24%, and <10.0 g/dL in 8%. Anemia rates were P/R, 38%; ND, 30%; in remission, 25%. Poor performance scores correlated positively with lower Hb levels; for patients with Hb <8.0 g/dL, 8.0–9.9 g/dL, 10.0–11.9 g/dL, and ≥12.0 g/dL, worse WHO scores of 2–4 were recorded for 43%, 41%, 25%, and 15%, respectively. During ECAS 1168 patients with data after enrollment never received ANT, and 40% were anemic at some time (at enrollment and/or at follow-up). Hb nadirs were approximately evenly distributed: 11.0–11.9 g/dL, 37%; 10.0–10.9 g/dL, 29%, and <9.0–9.9 g/dL, 34%. Anemia was infrequently treated with only 31.4% of patients receiving anemia treatment at any time. Anemia treatments administered and mean Hb at initiation were 14% epoetin alone ± transfusion ± iron (9.8 g/dL); 9% transfusion ± iron (8.4 g/dL); 8% iron (11.7 g/dL). Conclusions: Almost one-third of cancer patients who are not actively receiving ANT are anemic, including 25% of patients considered to be in remission. Anemia has a negative effect on performance, with worse WHO scores related to lower Hb levels. Anemia appears to be undertreated, with less than one-third of anemic patients receiving anemia treatment, and then only when Hb nadirs are <10.0 g/dL. To insure optimal management of cancer patients, all should be screened for anemia and receive the most effective anemia treatment. [Table: see text]