bluuebunny/crossref_metadata_2025 huggingface dataset:
Gabapentin for hot flashes in men: NCCTG trial N00CB
Authors: Loprinzi C. L. , Khoyratty B. S. , Dueck A. , Barton D. L. , Jafar S. , Rowland K. M. , Atherton P. J. , Marsa G. W. , Krook J. , Kottschade L.
Published: March 2020

9005

Background: Hot flashes can be a major problem in men with prostate cancer; effective non-hormonal options are needed. Methods: A four-arm, double-blinded, placebo-controlled randomized trial was developed to evaluate gabapentin for hot flashes. Men with bothersome hot flashes (at least 14/week) related to androgen deprivation therapy were randomized to receive either a placebo or gabapentin doses of 300 mg qd, 300 mg bid or 300 mg tid; men were treated for 4 weeks. Hot flashes numbers and scores (hot flash number times mean severity) were measured using a validated daily hot flashes diary. A one-week baseline period preceded initiation of study tablets. The primary endpoint was the average intrapatient difference in hot flash score between baseline and treatment termination. With the planned sample size of 50 evaluable patients per arm, the study provided 80% power to detect a difference in change from baseline at 4 weeks between each gabapentin arm and the placebo arm of 1.3 hot flashes per day or 3.3 points in hot flash score. Results: 223 patients were randomized between 12/21/2001 and 11/10/2006. The study arms were well balanced. The following table illustrates the percentage of baseline hot flash scores and frequencies during the fourth treatment week, compared to the baseline week for 179 eligible patients, utilizing the data available at time of this abstract preparation. Patients receiving 900 mg/d dose of gabapentin also reported significantly less hot flash distress and more hot flash control satisfaction than did the placebo group. The gabapentin was remarkably well tolerated, without any statistically significantly worse patient-reported side effects on the gabapentin arms. Conclusion: Gabapentin at the 900 mg/d dose can reduce hot flashes, in men receiving androgen deprivation therapy for prostate cancer.

No significant financial relationships to disclose.

[Table: see text]
How durable are behavioral changes? Results from FRESH START: A randomized controlled trial to improve diet and exercise behaviors in breast and prostate cancer survivors
Authors: Demark-Wahnefried W. , Clipp E. C. , Lipkus I. M. , Lobach D. , Peterson B. , Snyder D. C. , Sloane R. , Kraus W. E.
Published: March 2020

9019

Background: A healthy diet and regular exercise may improve the health, well-being and ultimate survival of cancer survivors. Last year, results of the FRESH START trial (n=543) were presented at ASCO; significant improvements in diet and exercise behaviors of breast and prostate cancer survivors were observed with two 10-month mailed print interventions - one that was sequentially- tailored and another using non-tailored print materials in the public domain (attention control). While both arms achieved significant improvements, those receiving the tailored intervention reported significantly greater changes (all p-values <.05). The durability of these changes, however, is not known. Methods: At 2-year follow-up, and after a 12-month wash-out, telephone surveys that were conducted at baseline and post-intervention (Diet History Questionnaire and 7-Day Physical Activity Recall) were repeated. Results: Ordinary Least Square analysis suggest that changes from baseline largely remain significant at 2-year follow-up for both interventions (see table ). Moreover, significant differences between arms are observed for dietary fat restriction and the practice of more lifestyle behaviors at goal level [i.e., consumption of ≥ 5 servings/day of fruits & vegetables (F&V), < 30% kcal from fat, and >150 min/week of exercise], with the tailored intervention arm achieving levels superior to those achieved in the attention control arm. Conclusions: Tailored and untailored interventions delivered over a 10-month period to cancer survivors exert durable effects on several lifestyle behaviors. However, the effects of the tailored intervention were initially more powerful and largely sustained over time (especially, with regard dietary fat restriction).

No significant financial relationships to disclose.

[Table: see text]
Does NSCLC patient-rated performance status predict survival more accurately than physician ratings?
Authors: Dajczman E. , Kasymjanova G. , Swinton N. , St-Pierre D. , Swanson T. , Kreisman H. , Agulnik J. S. , Cohen V. , MacDonald N. , Small D.
Published: March 2020

9022

Background: The Eastern Cooperative Oncology Group (ECOG) score is a well known predictor of survival, which impacts on treatment decisions. Patient (pt) rated activity level, using the Patient Generated Subjective Global Assessment (PG-SGA) scale, is identical in criteria to the ECOG scale used by physicians. We compared the patient rated activity level (Pt-PS) to physician rated PS (MD-PS), at baseline, and evaluated survival with respect to the 2 PS ratings. Methods: Pts with newly diagnosed advanced NSCLC (stages 3–4) completed a PG-SGA self rated questionnaire, which was then compared to the physician-generated ECOG score recorded prior to any treatment using a Wilcoxon signed rank test. Pts were treated with standard chemotherapy. Survival analysis was performed using a Kaplan Meier analysis and Cox regression. Results: 92 pts (M: F-48:44) with a mean age of 65 years (39–83) were included. 67 (73%) presented with stage 4 disease. 62 (67%) had an MD-PS of 0–1, whereas only 51 (55%) had a Pt-PS of 0 -1. MD-PS 3–4 was seen in 9 (10%), compared to 28 (30%) by Pt-PS. Pt-PS was significantly different from MD-PS in 48% of scores (p=0.003). When scores were not congruent, 29/44 (66%) pts evaluated themselves as having a worse PS than the physician. Survival analysis demonstrated that stage and functional status irrespective of method of reporting was predictive of survival (p=0.01 for MD-PS and p=0.001 for Pt-PS). However, when comparing median survival by method of performance status evaluation, Pt-PS was associated with superior stratification of survival than MD-PS ( table 1 ). Conclusions: Pt-PS and MD-PS are not congruent almost 50% of the time. Pt-PS allows for better stratification of survival and should be further evaluated in prospective trials.

No significant financial relationships to disclose.

[Table: see text]
Open-label safety and efficacy pilot trial of intraperitoneal bevacizumab as palliative treatment in refractory malignant ascites
Authors: El-Shami K. , Elsaid A. , El-Kerm Y.
Published: March 2020

9043

Background: One of the most burdensome complications of advanced cancer is the development of malignant ascites, impacting quality of life (QoL), gastrointestinal function, survival, and overall management costs. Recent studies have shown that malignant effusions arise in part from increased production and activity of vascular endothelial growth factors (VEGFs). VEGFs increase vascular permeability and establish an ideal environment for accumulation of malignant effusions. Methods: A pilot trial evaluating safety and efficacy of intraperitoneal administration of bevacizumab at 5 mg/kg monthly for as long as no disease progression or unacceptable toxicities are encountered. Patients with cytologically documented malignant ascites from any primary tumor refractory to standard therapy of diuretics, repeated paracentesis, and/or intraperitoneal chemotherapy were eligible. Patients were either off systemic therapy or had not had any changes in their systemic therapy for at least 4 weeks at the time of enrollment. Results: Between July 2006 and November 2006, 9 patients with refractory malignant ascites from colon cancer (3 pts), breast cancer (3 pts), uterine cancer (2 pts) and ovarian cancer (1 pt). Prior therapy included systemic chemotherapy and large volume paracentesis. Patients with ovarian and uterine cancer also received intraperitoneal cisplatin. All patients had rapid re-accumulation within 2 weeks of paracentesis before treatment. Patients were given intraperitoneal bevacizumab at 5 mg/kg monthly. Complications included grade I nausea in one patient, grade I abdominal pain in one patient, and partial small bowel obstruction in one patient that was managed conservatively. Malignant ascites resolved without reaccumulation or repeat paracentresis in 9/9 after a single intraperitoneal dose of bevacizumab over a median observation period of over two months. No objective tumor responses were observed. QoL assessment, pharmacokinetic studies of intraperitoneal Bevacizumab and pharmacodynamic studies on serum and ascites fluid VEGF are ongoing and will be reported. Conclusions: Intraperitoneal bevacizumab is a relatively safe and highly efficacious way to palliate the symptoms of refractory malignant ascites.

No significant financial relationships to disclose.
Doxorubicin, cardiac risk factors and cardiac toxicity in elderly patients with diffuse b-cell non-Hodgkin's lymphoma
Authors: Hershman D. L. , Eisenberger A. , Wang J. , Jacobson J. , Grann V. , McBride R. , Tsai W. , Neugut A.
Published: March 2020

9050

Background: Anthracyclines are known to cause acute and chronic cardiotoxicity. In a population-based sample of elderly patients with diffuse large B-cell lymphoma (DLBCL), we studied the cardiac effects of doxorubicin (DOX)-containing regimens and of pre-existing diabetes (DM), hypertension (HTN), and heart disease (HD). Methods: Patients aged =65 years diagnosed with DLBCL 1/1/1992–12/31/2000 in the SEER/Medicare database were grouped by treatment: no chemotherapy, doxorubicin-based chemotherapy, or other chemotherapy. We developed multivariable logistic regression models of the associations of DOX-based chemotherapy with demographic and clinical variables and pre-diagnosis DM, HTN, and HD. We then developed Cox proportional hazards regression models of the association between treatment and subsequent congestive heart failure (CHF) taking the predictors of treatment into account. Results: Of 6,413 patients with DLBCL, 2,536 (39%) received doxorubicin-based chemotherapy. DOX use was associated with later year of diagnosis, female gender, younger age, and being married. Black race (HR 0.50, 95% CI 0.33–0.75), comorbidities, preexisting CHF, HD, and DM (HR 0.73, 95% CI 0.62–0.86) were associated with decreased DOX use. The post-treatment HR for CHF following DOX treatment vs. no chemotherapy was 1.39 (95% CI 1.15–1.67); CHF risk increased with duration of DOX use. It was also associated with increasing age, comorbidities, black race, DM, HTN, and HD. There was a significant interaction between race and DOX (P=0.01); For black patients treated with DOX the HR for CHF was 3.4, as compared to a HR of 1.3 for white patients. Conclusions: Among patients with DLBCL, black race, CRFs and pre-existing HD are all associated with both a reduced likelihood of receiving anthracyclines, and an increased risk of CHF. We have previously found a powerful effect of DOX on survival in this patient population; thus, for most patients, the benefits of treatment would appear to outweigh the risks of cardiac toxicity. However, as the number of long-term survivors grows, the need for research on the side effects of treatment, on host factors that may increase the risk of adverse effects, and on ways to minimize such risks will also grow.

No significant financial relationships to disclose.
A double-blind, randomized, placebo-controlled study of fentanyl buccal tablet (FBT) in opioid-tolerant patients with chronic cancer pain and breakthrough pain
Authors: Slatkin N. , Xie F. , Segal T. , Messina J.
Published: March 2020

9057

Background: Episodes of cancer-related breakthrough pain (BTP) often peak in intensity in minutes. Pain relief with traditional, short-acting oral opioids is often not achieved for =30 min. Fentanyl buccal tablet (FBT) has a rapid onset of analgesia. This double- blind, randomized, placebo-controlled study evaluated the efficacy and safety of FBT in opioid-tolerant patients with cancer and BTP. Methods: After open-label titration to establish a successful dose of FBT, patients were randomized to prespecified, double-blinded sequences of 10 tablets (7 FBT, 3 placebo). Pain intensity (PI) was assessed from 5 to 120 min post dose. The primary efficacy measure was the sum of PI differences (PIDs) for the first 60 min (SPID60); secondary measures included PIDs, =33% and =50% improvements in PI, and global medication performance (GMP). Use of supplemental BTP medication and adverse events (AEs) were reported. Results: 129 patients were enrolled; 87/125 treated (70%) identified an effective FBT dose and entered the double-blind phase. SPID60 significantly favored FBT vs placebo (mean±SEM, 9.7±0.63 vs 4.9±0.50; p<0.0001). PID differed significantly vs placebo at 10 min (mean±SEM, 0.9±0.09 vs 0.5±0.09; p<0.0001) and at all time points through 2 hr (p<0.0001). Improvements in PI of =33% and =50% from baseline occurred in a larger proportion of episodes following FBT vs placebo from 10 min (16% vs 10% and 7% vs 4%, respectively; p<0.05) through 2 hr (74% vs 38% and 66% vs 28%; p<0.0001). Ratings of GMP were superior for FBT vs placebo at 60 and 120 min (p<0.0001). Supplemental opioids were required for approximately 3 times more BTP episodes following placebo compared with FBT. AEs were typical for opioids, e.g. nausea (13%), dizziness (11%), fatigue (8%), and constipation (6%). Application site-related AEs occurred in 12 patients (10%). A total of 11/125 (9%) patients had =1 serious AE; these were considered not/unlikely to be related to study drug. Conclusions: FBT was effective and well tolerated in the management of BTP in opioid-tolerant patients with cancer-related pain, with an early onset of analgesia and a sustained duration of effect.

No significant financial relationships to disclose.
Secondary causes of cancer-related anorexia: Recognition in daily practice by a novel checklist, a pilot study
Authors: Omlin A. G. , Strasser F.
Published: March 2020

9058

Background: Secondary - potentially reversible - causes of cancer-related anorexia, a common and devastating complication of advanced cancer, remain poorly recognised in daily practice. To explore the frequency of SecAn and evaluate the practice- guiding-potential (PGP) of a novel clinical assessment checklist (CL-SecAn). Methods: The 11 item CL-SecAn is based on literature review and multiprofessional clinical expert opinions. Patients rate the answers to the questions “I feel anorectic because of [i.e. stomatitis]” by an 1–4 categorical scale (no, little, moderate, a lot). Consecutive patients of an interdisciplinary palliative-oncological outpatient “nutrition & fatigue” clinic (NF-clinic) and of a multicenter cross-sectional advanced cancer pain study completed the CL-SecAn. Charts of the NF-clinic were retrospectively reviewed for onset or change of therapeutic interventions (Tx-SecAn) focused on identified causes of SecAn. Patients with (rating 3 or 4) or without (1 or 2) one of the 11 SecAn causes were compared to estimate PGP. In addition, matched (age, sex, tumor, cachexia) “regular” out-patients are compared to NF-clinic patients for Tx-SecAn. Results: SecAn was present (defined as =3/4) in 63 of 113 (56%) patients (53 NF-clinic, 60 study; f:m 45:68; age 64 [median, range 25, 88]; 30% gastrointestinal, 20% lung, 13% prostate, 10% urogenital, and 17% other cancer, 10% lymphoma). SecAn causes were: stomatitis 4%, dysgeusia 19%, dysphagia 8%, epigastric pain 9%, abdominal pain 14%, constipation19%, diarrhea 5%, defecation after a meal 2%, pain 12%, dyspnoea 3% and fatigue 13%. In 36 (32%) patients more than one cause was present. Tx-SecAn for dysgeusia was applied in 7 of 15 patients (46%) with and 3 of 38 (8%) without Sec-An Dysgeusia. For constipation, Tx-SecAn was modified in 70% with and 27% without Sec-An constipation. The other 9 Sec-An were analysed accordingly. The case-control study is currently ongoing. Conclusions: SecAn causes seem to be common in advanced cancer patients. The CL-SecAn carries a Practice-Guiding-Potential, at least for some of the 11 SecAn causes, its potential might be underrecognized in frequently treated syndromes, such as constipation. Future research will investigate further the impact of CL-SecAn.

No significant financial relationships to disclose.
Attitudes on terminal sedation, physician assisted suicide and euthanasia in oncology personnel, oncological patients and relatives
Authors: Maier V. , Kunitz A. , Thuss-Patience P. C.
Published: March 2020

9068

Background: This survey was performed to elucidate and compare the attitudes on end of life management of participants actively affected by/involved in oncology either as a doctor, nurse, patient or a relative. Methods: In this questionnaire based survey performed in Berlin, Germany, approved by the local ethics committee, 4 groups of participants (oncology doctors (D), oncology nurses (N), oncology patients (P) and relatives (R)) were asked about their attitudes on the management of terminally ill oncological patients. Participants were asked to mark their maximal ethically accepted management of a specific case from a series of 10 destinct management options (opt). These options were destilled into 4 groups ranging from sole pain control (SYM)(opt 1) at the bottom of the scale, through to terminal sedation (SED)(opt 2–4), physician assisted suicide (SUI)(opt 5–7) and finally active euthanasia (EUT)(opt 8–10) at the top of the scale. Each participant marked his attitude by putting himself in the role of the treating physician, in the role of the patient described in the case and in the role of a legislative body. Results: 435 questionnaires distributed, 185 returned (42.5%). Participants: D: 58 N: 61 P: 30 R: 36. All participants answering 1) in the role of a treating physician, 2) in the role of a terminally ill patient, 3) in the role of a legislative body. Table shows attitudes of a) all participants and of the 4 subgroups of participants b) doctors, c) nurses, d) relatives, e) patients. Conclusions: Only a minority of participants would themselves perform or assist in active life terminating measurements (SUI+EUT)(23%), more participants would wish for themselves active measurements (SUI+EUT)(30%) and significantly more participants are for legislation to allow active measurements (SUI+EUT)(47%). Medical personnel (doctors equally as nurses) are significantly more reluctant to assist/perform or wish for themselves active measurements (SUI+EUT) than relatives and patients.

[Table: see text]

No significant financial relationships to disclose.
Cytokine levels in patients (pts) with colorectal cancer and breast cancer and their relationship to fatigue and cognitive function
Authors: Vardy J. L. , Booth C. , Pond G. R. , Zhang H. , Galica J. , Dhillon H. , Clarke S. J. , Tannock I. F.
Published: March 2020

9070

Background: Cytokines have been associated with fatigue and cognitive dysfunction. Here we evaluated plasma cytokine levels in pts with colorectal cancer (CRC) and breast cancer (BC) who were free of evident disease, and in healthy volunteers. Methods: Serum levels of 10 cytokines were measured using a LiquiChip assay on 251 subjects. CRC pts (n=136, ages 23–75) were evaluated at baseline (mean 8 weeks post-surgery [n=107] or before surgery [n=29]), with repeat measures at 6 months (56 post chemotherapy [CT], 14 without CT) and 12 months (32 post CT, 7 without CT). BC pts (n=51, ages 29–60) were within 5 years of diagnosis (33 after adjuvant CT). Healthy volunteers (n=64) had ages 20–62. Cancer pts completed questionnaires for fatigue & QOL (FACT-F), anxiety/depression (GHQ), and perceived cognitive function (FACT-COG); they had neuropsychological assessment. Results: Cytokines were elevated in all cancer groups compared to healthy controls (p-values <0.001; selected data in table ). Values were highest after surgery but remained significantly higher than healthy controls at 6–60 months after diagnosis, with a trend to being higher in cancer patients who had not received CT. There was a trend to elevated cytokines being associated with greater fatigue and cognitive impairment in both CRC and BC, but no association with QOL or anxiety & depression. Conclusions: Cytokine levels were elevated in all cancer groups compared to healthy volunteers and remained elevated up to 5 years post diagnosis; they may be associated with cognitive dysfunction and fatigue.

[Table: see text]

No significant financial relationships to disclose.
Methylnaltrexone treatment of opioid-induced constipation in cancer patients
Authors: Karver S. B. , Slatkin N. E. , Thomas J. , Israel R. J.
Published: March 2020

9081

Background: Constipation is a common and distressing side effect of opioid treatment particularly in patients with cancer. Two phase 3 trials (Studies 301 and 302) reported that subcutaneous (SC) methylnaltrexone was well tolerated and effective in inducing laxation in patients with advanced illness with opioid-induced constipation (OIC) while maintaining central analgesia. Aims: To evaluate improvement in constipation in cancer patients treated with methylnaltrexone in the above studies. Methods: In Study 301, 124 cancer patients received a single dose of methylnaltrexone (SC 0.15mg/kg, 0.30mg/kg) or placebo. In Study 302, 78 cancer patients received either 0.15mg/kg SC QOD methylnaltrexone for 2 weeks (total of 7 doses) or placebo. Patients had a life expectancy of 1–6 months, no laxation within 48 hours, and were maintained on stable opioids and baseline laxatives. The primary efficacy endpoints were laxation within 4 hours after a single or first dose of study drug and laxation within 4 hours for at least 2 of the first 4 doses (Study 302). The secondary endpoints were laxation within 24 hours, pain scores, and opioid withdrawal symptoms. Results: A majority of the methylnaltrexone-treated cancer patients had a laxation within the first 4 hours of study drug administration ( Table ). There were no clinically significant changes in pain scores or opioid withdrawal symptoms. Conclusions: Our results demonstrate that in cancer patients with advanced illness and OIC, methylnaltrexone significantly improved constipation, without loss of pain control or opioid withdrawal.

[Table: see text]

No significant financial relationships to disclose.
Cetuximab-related hypersensitivity reactions associated with pre-existing cetuximab-specific IgE antibody
Authors: Chung C. H. , Chan E. , Berlin J. , Gilbert J. , Yarbrough W. , Satinover S. , Murphy B. , Slebos R. J. , Hatley T. , Platts- Mills T.
Published: March 2020

9097

Background: Cetuximab is a chimeric (mouse/human) IgG1 monoclonal antibody against the epidermal growth factor receptor and is approved for use in patients (pts) with colorectal cancer and head and neck squamous cell carcinoma. Hypersensitivity reactions caused by cetuximab (C-HSR) have been reported; however, the mechanism underlying these reactions is unknown. We hypothesize that C-HSR are mediated by pre-existing cetuximab-specific IgE antibodies (C-IgE). Methods: A total of 140 serum samples were obtained under IRB approved protocols and retrospectively analyzed across 2 cohorts: 1) 71 pretreatment sera from cetuximab-treated pts collected from multiple centers (47 pts with no HSR and 24 pts with any grade HSR; samples were biased for HSR pts), and 2) 69 sera from healthy volunteers in the Nashville TN area. The samples were analyzed for total-, cetuximab-specific and mouse-specific IgE levels using a modified ImmunoCAP assay (Phadia US Inc.). Severe HSR was defined as grade 3/4 reactions during the first infusion by NCI CTC version 3.0 Allergic reaction/hypersensitivity criteria by a reviewer blinded to the immunoCAP assay results. Results: Of the 71 cetuximab-treated pts from cohort 1, 21 experienced severe HSR by retrospective evaluation. All C-IgE(+) pts (15/15) experienced severe HSR and were immediately discontinued from therapy. Of the remaining 6 severe HSR pts with C-IgE(-), 4 pts were re-challenged and completed their cetuximab infusion without any further reaction, suggestive of a non-IgE mediated mechanism, while 2 pts were not re-challenged. Also, the C- IgE(+) pts tended to have higher levels of total IgE compared to the C-IgE(-) pts. All 47 non-HSR pts were C-IgE(-). Mouse-specific IgE was not detected in any sera from the pts. Analysis of sera from healthy volunteers from the cohort 2 revealed that 15/69 (21.7%) were C-IgE(+), suggestive of pre-existing C-IgE; however, the association with C-HSR could not be made. Conclusion: Our data suggest that C-IgE antibodies are present prior to treatment and appears highly predictive of severe HSR during the first infusion; however, IgE-mediated reactions may not account for all cases of HSR. Prospective validation of the association between C-IgE and cetuximab-induced HSR is warranted.

[Table: see text]
Cognitive function and fatigue in cancer patients after chemotherapy: A longitudinal cohort study in patients with colorectal cancer (CRC)
Authors: Vardy J. L. , Rourke S. , Pond G. R. , Galica J. , Park A. , Dhillon H. , Clarke S. J. , Tannock I. F.
Published: March 2020

9099

Background: There is growing evidence that fatigue and cognitive dysfunction can affect cancer survivors. Here we evaluated these symptoms in patients with CRC in a longitudinal prospective study. Methods: Patients with localized CRC were evaluated for cognitive function and fatigue at baseline (mean 8 weeks post-surgery or before neoadjuvant therapy), 6 & 12 months. Group A (Stage III/high risk II) received chemotherapy (CT) and group B (Stage I/II) received no CT. Pts had neuropsychological (NP) assessment with traditional tests and CANTAB, a computerized NP battery. They completed concurrent questionnaires for fatigue & QOL (FACT-F), anxiety/depression (GHQ), and perception of cognitive function (FACT-COG). Blood tests evaluated cytokine levels, blood clotting factors, sex hormones and apolipoprotein genotyping as potential causal factors. Primary endpoints were cognitive function (traditional NP tests) and fatigue. Associations between test results, demographic and disease-related factors were sought. Results: Baseline data are available for 182 pts: 127 group A, and 55 group B, with follow-up at 6 and 12 months for 71 and 39 pts. Mean age was 57 years and 62% were male. At baseline (pre CT): 30% had cognitive impairment on traditional NP tests & 20% on CANTAB; 25% reported moderate fatigue and 10% extreme fatigue. At 6 months there was no significant difference on objective NP testing between the groups or in perceived cognitive impairment (median FACT- COG 82 vs 88, p=0.34). CT pts had more fatigue (median FACT-F 75 vs 91, p<0.001). At 12 months CT pts tend to have more cognitive impairment on traditional NP tests (26% vs 0%, p=.09), more perceived cognitive impairment (13.5% vs 0%, p=.57) & greater fatigue (16% vs 0%). Cytokine levels were elevated in all groups at all time points compared to healthy volunteers. There was a trend to higher cytokine levels with greater fatigue and worse cognitive impairment. Fatigue, QOL and anxiety and depression were highly correlated. Conclusions: Cognitive impairment is present in some pts prior to CT and there is a trend for CT pts to have worse cognitive impairment at 12 but not at 6 months. Fatigue is associated with CT. Cytokine levels remained elevated in all groups compared to healthy volunteers.

No significant financial relationships to disclose.
Mitigating functional performance decrement in cancer patients undergoing treatment
Authors: Anton P. M. , Dennehy C. A.
Published: March 2020

9105

Background: It is well-documented that treatment side-effects cause physical and psychosocial de-conditioning in cancer patient. Decrease in functional performance (FP), as measured by activities of daily living (ADL), is a major contributor to a decline in patient quality of life (QOL). Relatively little information is available on the effects of a specific exercise regimen targeting muscle groups/energy systems involved in FP. Methods: 30 male and female cancer patients receiving treatment were randomly assigned to either the experimental (EX) or control (C) groups. EX participated in two exercise sessions per week for 17 weeks. Sessions included a combination of aerobic, resistance, flexibility, and balance training. C did not participate in any structured exercise. Data were collected post-diagnosis (1), post- surgery (2), at 9 weeks post-diagnosis (3), and at 17 weeks post-diagnosis (4). Measurements included resting heart rate (RHR), fatigue, physical activity level (PA), QOL, and the FP tasks of: treadmill walking (TRED), stair climb/descent (STAIR), lifting/carrying (CARRY), sit to stand (STAND), and balance (REACH). Results: Factor analysis yielded four variables: FP1 = [(0.5 × TRED) - (0.5 × RHR)]; FP2 = [(STAIR) + (CARRY) + (STAND)]/3]; FP3 = [(0.333 × QOL) + (0.333 × PA) - (0.333 × FT)]; FP4 = REACH. Repeated-measures ANOVA with within-subjects contrasts detected significant differences between groups. No significant differences existed at 1 or from 1 to 2. Significant differences were found on all variables from 1 to 4, 1 to 3 and 3 to 4 (p < 0.001) (significant improvement for experimental group vs. significant decline for control group). Mean changes for the experimental vs. control groups from 1 to 4 are as follows: FP1 (+65.5 vs. -29.5); FP2 (-5.3 vs. +3.6); FP3 (+1.8 vs. -3.4); FP4 (+1.7 vs. -0.81). Conclusions: Specifically-designed exercise interventions promote positive adaptations that elicit significant improvement in ADL, QOL, and decrease fatigue. Prescriptive exercise is a viable therapy during treatment for mitigating side effects and avoiding de-conditioning.

No significant financial relationships to disclose.
Effects of intravenous (IV) iron supplementation on responses to every-3-week (Q3W) darbepoetin alfa (DA) by baseline hemoglobin in patients (pts) with chemotherapy-induced anemia (CIA)
Authors: Pinter T. , Mossman T. , Suto T. , Vansteenkiste J.
Published: March 2020

9106

Background: Pts with CIA receiving erythropoiesis-stimulating agents (ESAs) may benefit from IV iron supplementation. This randomized, multicenter, open-label, 16-week, phase IIIb study evaluated the safety and efficacy of darbepoetin alfa in pts with CIA who also received IV iron versus oral iron/no iron. This exploratory analysis presents the clinical outcomes by subgroups based on baseline (BL) hemoglobin (Hb). Methods: Eligible pts were of legal age, had a non-myeloid malignancy, and had CIA (BL Hb < 11g/dL). All pts received DA 500 mcg administered Q3W using the Aranesp (darbepoetin alfa) prefilled SureClick autoinjector. Patients were randomly allocated 1:1 to receive either DA plus 200 mg IV iron (200 mg Q3W with DA Q3W or two 100 mg doses within 3 weeks) or DA plus oral iron/no iron. Randomization was stratified by tumor type and BL Hb category (< 10 or = 10 g/dL). The primary endpoint was the percentage of pts achieving a hematopoietic response (Hb = 12 g/dL or an increase = 2 g/dL). Results: A total of 396 pts were randomized and received = 1 dose of DA (IV iron arm = 200; oral iron/no iron arm = 196). Mean (SD) age was 61.0 (11.5) years; 61% (n = 240) were women; 28% (n = 111) had lung or gynecological tumors; and 45% (n = 178) had BL Hb < 10 g/dL. Pt demographics were similar between arms. Clinical outcomes are shown in the table by BL Hb. Conclusions: DA 500 mcg Q3W with IV iron supplementation appeared to improve clinical outcomes in this study, especially in pts with BL Hb < 10 g/dL; more pts achieved a hematopoietic response, fewer received transfusions, and more achieved the target Hb (= 11 g/dL) compared with those receiving oral iron/no iron. Also, in both treatment arms, pts with BL Hb = 10 g/dL demonstrated better clinical outcomes than pts with BL Hb < 10 g/dL. Benefits associated with initiating ESA treatment on time, ie before pts Hb falls < 10 g/dL, have been suggested previously (Lyman and Glaspy, Cancer 2006).

[Table: see text]

No significant financial relationships to disclose.
Levetiracetam for the treatment of hot flashes: A pilot study
Authors: Thompson S. L. , Bardia A. , Tan A. , Barton D. , Kottschade L. , Sloan J. , Christensen B. , Smith D. , Loprinzi C.
Published: March 2020

9116

Background: Hot flashes affect 75 % to 90 % of women transitioning to menopause and are a major cause of morbidity among breast cancer survivors. Levetiracetam, a popular anticonvulsant, is a centrally active agent that anecdotally appeared to reduce hot flashes in clinical practice. This phase II trial sought to evaluate the efficacy of levetiracetam in reducing hot flashes among women with a history of breast cancer or women who did not wish to take estrogen therapy for fear of an increased risk of breast cancer. Methods: Women who were experiencing bothersome hot flashes (≥ 14 times per week, for ≥ 1 month) were eligible. A single arm pilot study design based on previous work was used with a planned sample size of 30 patients. The patients did not receive any study medication during the first week (baseline week). At the beginning of the second week, patients were started on levetiracetam (500 mg), and were to increase the dose by 500 mg each week to a goal of 1,000 mg twice daily. Hot flash diaries were completed daily. The primary endpoint was hot flash score (frequency times average severity). The change from week 1 (baseline) to week 5, the last treatment week, was analyzed by paired t-test and related Wilcoxon procedures. Results: A total of 30 women were enrolled onto this study in eight months. All patients were eligible. 19 women completed all 4 weeks of the study treatment and provided complete data. After treatment with levetiracetam for 4 weeks, mean hot flash scores were reduced by 57% (95% CI 39%-75%), while mean hot flash frequencies were reduced by 53% (95% CI 38%-68%), reductions being greater than what would be expected with a placebo. There were significant improvements, compared to baseline week data, in sweating, hot flash distress, and satisfaction with hot flash control. Eight subjects stopped the study drug due to treatment related adverse events (grade I/II), with the most frequently reported being somnolence, fatigue and dizziness. Conclusions: While levetiracetam appears to be a promising therapy for the treatment of hot flashes, further study is needed to better substantiate the toxicity and efficacy of this drug before it can be more definitively recommended for use in clinical practice.

No significant financial relationships to disclose.
Renal insufficiency in bone metastasis cancer patients: Prevalence and implications on anticancer drugs management, subgroup analysis of the IRMA study
Authors: Janus N. , Le Tourneau C. , Launay-Vacher V. , Gligorov J. , Rixe O. , Pourrat X. , Beuzeboc P. , Morere J. , Deray G. , Oudard S.
Published: March 2020

9121

Background: The IRMA study reported the high prevalence of renal insufficiency (RI) in 4684 solid tumour patients, with a glomerular filtration rate (GFR) <90 ml/min for 50–60%. Furthermore, 80.1% were receiving nephrotoxic anticancer drugs and 79.9% drugs necessitating dosage adjustment. We present the results for IRMA patients with bone metastasis (BM). Methods: Subgroup analysis of IRMA patients with BM. Data collected: sex, age, weight, serum creatinine (SCR), bone metastasis (BM) and anticancer drugs. The prevalence of SCR>110 μmol/L was assessed. GFR was estimated with Cockcroft-Gault (CG) and abbreviated MDRD (aMDRD) formulae. Drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Chi-square test was used to compare the prevalence of RI between patients with BM and patients without, for all patients and for breast cancer (BC) ones. Results: 1,000 patients (BC 577) with BM were included: median age 60, mean 59.8, weight 66 kg, 659 women. The prevalence of SCR>110 μmol/L was 8.3%. That of GFR<90 ml/min was 57.9% with CG and 54.7% with aMDRD. 83.4% of treated patients received at least one drug needing dosage adjustment (or no data) and 69% received at least one nephrotoxic drug. The prevalence of RI was not statistically different between patients with or without BM. However, the prevalence of RI was significantly higher in BC patients with BM as compared to BC patients without BM (62.1 versus 56.7 %, p=0.04). Conclusions: RI is highly frequent in cancer patients with BM. Appropriate evaluation of renal function necessitates CG or aMDRD calculation. In those patients, and especially in breast cancer patients with BM, anticancer drugs should be cautiously selected regarding their potential renal toxicity and need for dosage adjustment.

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No significant financial relationships to disclose.
Risk assessment model for first-cycle chemotherapy-induced neutropenia (CIN) among lung cancer (LC) patients: DELFOS study
Authors: Rifà J. , González Larriba J. L. , Casas Fernández de Tejerina A. , López Pousa A. , Febrer L. , Carrato A.
Published: March 2020

9132

Background: CIN is common in LC patients (pts) who receive myelosuppressive chemotherapy and contributes to therapy induced morbidity and mortality therefore having strong impact both on health and on health care systems. The objective of the present research study is to determine a predictive model for first-cycle CIN in pts with LC in Spain. This will help to establish appropriate protocols in routine patient care, hence improving clinical decision making. Methods: Data were obtained from the DELFOS Study, a multicentre non-interventional prospective-cohort study in Spain. This study has completed enrolment and data are available for this planned analysis. To obtain the predictive logistic regression model (LRM), the hierarchical principle was followed as a way to enable results replication. The model was implemented for CIN defined as neutropenia grade = 3 (with or without body temperature = 38 C°). A receiver operating characteristics (ROC) Curve was used to determine the model's sensitivity and specificity. Results: A total of 210 pts with LC (86 % male; mean age: 63 yrs (SD: 10); ECOG = 2;) were included in 65 Spanish medical oncology health centres. A selection process of potentially relevant factors was performed among socio-demographic, clinical and biochemical parameters collected. The LRM obtained predicted the CIN at first-cycle (pChi-sq < 0.0005) through the following factors: baseline platelet count (BPC), baseline haemoglobin (Hb) and type of chemotherapy treatment. In that sense, lower BPC was associated with higher risk of CIN (p<0.0005; OR=1.01; 95%CI (1.005, 1.016)) and the same happened with lower baseline Hb (p=0.017; OR=1.4; 95%CI (1.06, 1.8)). Pts in Platinum-based Chemotherapy showed higher risk of CIN compared to those in combination of Platinum and Taxane-based Chemotherapy (p=0.027; OR=5.5; 95%CI (1.2, 24.9). Inherent sensitivity and specificity of the equation were, respectively, 70.4% and 73.2%. Conclusions: A statistically significant risk predictive model for first-cycle CIN in pts with LC in Spain was implemented. Three predictive factors were identified. Baseline platelet count and baseline Hb were inversely associated with toxicity. Toxicity increased for pts with Platinum-based Chemotherapy regimens.

No significant financial relationships to disclose.
A phase II randomized, placebo-controlled, double-blind study of the efficacy and safety of RC-1291 (RC) for the treatment of cancer cachexia
Authors: Garcia J. , Boccia R. V. , Graham C. , Kumor K. , Polvino W.
Published: March 2020

9133

Background: Cancer cachexia is closely correlated with poor outcome and poor survival. RC is an oral ghrelin mimetic with orexigenic and anabolic activity. Methods: A phase II trial enrolled 81 patients with cancer, performance scores of 0–2, and weight loss of 5% or more within 6 months prior to enrollment at 17 sites in the US. Patients were randomized to treatment with two placebo (PL) or two 25 mg RC capsules taken once daily for 12 weeks. Outcome measures included lean body mass (LBM), total body mass (TBM) by DEXA (central reading), scale weight, handgrip strength (HS) and QOL measures. Biochemical markers included IGF-1 and IGFBP-3. In the per protocol analysis (32 RC, 28 PL) more than 20 cancer types were represented; the most common were lung (n=13) and colorectal cancer (n=15). The two treatment groups were balanced at baseline except for (RC vs PL, respectively): gender (66 % male vs 57 %), TBM (60.9 kg vs 65.3 kg), and HS (53.8 kg vs 56.6 kg). The analyses (repeated measures ANOVA without imputation) included all available data from the patients. Results: TBM and LBM (primary endpoint at 8 wks) were significantly increased vs. PL at wks 4 and 8 and at wks 4, respectively. The magnitude of the increase vs. baseline was stable from wk 4 through wk 12 during RC treatment for both TBM and LBM. HS was increased at significantly at wk 8. IGF-1 and IGFBP-3 significantly increased at wks 4, 8, and 12. No significant differences were found on the QOL or scale weight measures. RC was well tolerated. Patients having any AEs were 96% vs 87% and SAEs were 32% and 26% for RC and PL, respectively. The percent of patients and types of AEs were similar; possible exceptions included cardiac events and infections (11% vs 3% and 30% vs 42%, RC vs PL, respectively). Conclusions: In this randomized, double-blind, placebo-controlled trial, RC treatment led to improvements in LBM, TBM and HS. RC-1291 is a promising potential therapeutic agent for the treatment of cancer cachexia.

No significant financial relationships to disclose.
Update on the development of the international neuroblastoma risk group (INRG) classification schema
Authors: Cohn S. L. , London W. B. , Monclair T. , Matthay K. K. , Ambros P. F. , Pearson A. D.
Published: March 2020

9503

Background: Modern treatment strategies for neuroblastoma (NB) are tailored according to patient risk. However, it is not currently possible to compare the results of clinical studies conducted around the globe because the criteria used to define risk are not uniform. A committee of international investigators with expertise in NB have worked during the past 2 years to develop a uniform International NB Risk Group (INRG) Classification System for pre-treatment stratification. Methods: Investigators from North America and Australia (COG); Europe (SIOPEN and Germany), and Japan collated data on 8,800 children with NB diagnosed between 1990 and 2002. Survival tree regression analyses tested 13 potential prognostic factors. Tumor differentiation, MKI, and diagnostic category were evaluated individually in lieu of the International NB Pathology Classification (INPC) system to determine if these histologic features had prognostic value independent from age. To stage patients at the time of diagnosis prior to surgery, a new staging system was developed (INRGSS) based on the presence or absence of image-defined risk factors (IDRFs) and metastases. Results: Since statistical analyses demonstrated support for an optimal age cut- off between 14–19 months, 18 months was selected. In addition to age, stage, MYCN amplification, tumor differentiation, ploidy, and genetic aberrations of 11q were found to be the most highly prognostically significant factors. These clinical and biological factors were combined to define 15 INRG pre-treatment groups. Patients with low- (3 groups), intermediate- (4 groups), high- (4 groups), or ultra-high-risk NB (4 groups) had EFS of ≥85%, >70–85%, >50–70%, or <50%, respectively. Conclusion: International collaborative studies in NB will be greatly facilitated by the INRG classification system which will allow comparisons of different risk-based therapeutic approaches in homogeneous patient cohorts.

No significant financial relationships to disclose.
Response and toxicity to a dose-intensive multi-agent chemotherapy induction regimen for high risk neuroblastoma (HR-NB): A Children's Oncology Group (COG A3973) study
Authors: Kreissman S. G. , Villablanca J. G. , Diller L. , London W. B. , Maris J. M. , Park J. R. , Reynolds C. P. , von Allmen D. , Cohn S. L. , Matthay K. K.
Published: March 2020

9505

Background: Myeloablative consolidation improves outcome for HR-NB pts, especially for pts in CR prior to consolidation. We assessed the toxicity and CR+VGPR rate of a dose-intensive multi-agent chemotherapy induction based upon the N7 regimen (JCO 22:4888, 2004) prior to myeloablative consolidation and peripheral blood autologous stem cell transplant (ASCT). Methods: Between 2/2001 and 3/2006, 489 eligible newly diagnosed HR- NB pts received the following induction consisting of 6 cycles of chemotherapy q 21 days. Cycles 1, 2, 4 & 6: cyclophosphamide 4.2 g/m2, doxorubicin 75 mg/m2, and vincristine 2 mg/m2 and Cycles 3 &5: cisplatin 200 mg/m2 and etoposide 600 mg/m2. Surgical resection of primary occurred after cycle 5. Following induction pts received purged or unpurged ASCT (as randomized), radiation, and then 13-cis-retinoic acid (13-cis-RA). Response was assessed after cycles 2 & 6 using the International Neuroblastoma Response Criteria and analyzed as intent-to-treat. Results: Median age was 3.1 yrs, 44% of 392 tumors tested had MYCN amplification. Fourteen pts (3%) died during induction (5 infection, 4 bleed into tumor, 4 compromised organ function from tumor, 1 unrelated to tumor/therapy). Patients experienced the following grade 3 & 4 toxicities at least once during induction: neutropenia 70%, thrombocytopenia 71%, hearing loss 6%, cardiac function 2% and renal function 3%. Documented infection occurred in 24% of cycles (90% bacterial, 3% viral, 7% fungal). Responses among the 489 pts at end of induction were CR 24%, VGPR 28%, PR 26%, SD 7%, and PD15%, with morphologically detectable bone marrow (BM) disease cleared in 87% and no disease remaining by MIBG scan in 55% of pts MIBG positive at baseline. Conclusions: Despite increased dose intensity of this regimen, toxicity was not excessive compared to prior HR-NB regimens. In a multi-center setting, the A3973 induction chemotherapy achieved morphologic BM clearance in 87% of pts prior to consolidation. The CR/VGPR rate of 52% is similar to that of prior less intensive regimens. The impact of this induction response on survival within the context of ASCT and 13-cis-RA on COG A3973 will be determined with longer follow-up.

No significant financial relationships to disclose.