bluuebunny/crossref_metadata_2025 huggingface dataset:
Longitudinal evaluation of fine motor deficits in children with leukemia
Authors: Hockenberry M. J. , Krull K. , Moore I. M. , Pasvogel A. , Gregurich M. , Kaemingk K.
Published: April 2020

8559

Background: Fine motor assessments are important tools to use in screening children undergoing treatment for acute lymphoblastic leukemia (ALL) that may provide decisive data that can reveal subtle changes in neurodevelopment over time. Methods: Fine motor and visual-motor skills were assessed longitudinally in a group of 83 children receiving treatment for ALL. Children in this study had the first fine motor assessment at an average of 8 weeks into treatment and had already received several doses of Vincristine. Fine motor and visual-motor skills assessments were repeated at years 1 and 2 into therapy. The mean age at time of first assessment was 7.2 years and 58% were female. Results: Fine motor speed deficits were evident at the first assessment, and for many, continued to be problematic at Years 1 and 2. In addition to fine motor speed deficits, a significant decline in visual motor integration skills was noted from the baseline level (p = 0.019). Visual motor integration skills observed at Years 1 and 2 were predicted by the baseline performance on the Purdue Pegboard test. Our results indicate that the factors underlying these declines in higher-level skills begin within six months of the onset of chemotherapy. Conclusions: Early reductions in fine motor speed, possibly due to Vincristine, steroids and/or acute Methotrexate toxicity, may lead to reduced visual motor integration and construction abilities. The reduced fine motor skills, which predict eventual declines in visual motor integration, may be part of the underlying process for reduced perceptual abilities and nonverbal intellect often reported in long-term follow-up studies. For children with ALL, motor and sensory-perceptual examinations during treatment may identify those most at risk for significant long-term effects interfering with integration of visual spatial construction. These basic processing skills are necessary elements to the development of higher-level cognitive abilities, including nonverbal intelligence and academic achievement, particularly in arithmetic and written language. Early identification of reduced processing skills can provide an opportunity to identify at risk patients and intervene prior to reduction in these higher-level skills. Supported by NIH/NICHD RO-1 Funding: Grant number HD 37816

No significant financial relationships to disclose.
What is a clinically significant improvement in the intensity of fatigue among cancer patients?
Authors: Reddy S. G. , Pace E. , Zhang T. , Bruera E.
Published: April 2020

8560

Background: Fatigue is the most common symptom in cancer patients. The FACIT-F fatigue subscale and the ESAS Fatigue 0–10 are the most commonly used scales for research and clinical care, respectively. However, clinically significant improvement has not been well established. Methods: We reviewed the data from 3 RCTs of fatigue in 194 patients. In all cases patients completed the FACIT-F and ESAS at baseline and Day 8. All patients also provided a global benefit score [1=not beneficial, 7=greatly important] during Day 8 reflecting their global perception of fatigue improvement. All patients who reported their global perception as ≥ 4 [moderate improvement, consistent benefit] were considered to have a clinically significant improvement. We determined the median [25–75% quartiles] change in ESAS and FACIT-F as well as their screening performance when using the clinically significant difference to define responder status. Results: Mean age was 56 ± 12 years. 72 patients [37%] were female. Median baseline FACIT-F and ESAS scores were 18 ± 8 and 7.5 ± 1.7, respectively. Patients who reported a clinically significant improvement had a median [quartiles] change of 4 [3–6 ] in ESAS and 17 [9–25 ] in FACIT-F sub score resulting in a specificity of 72% for ESAS and 93% for FACIT-F, respectively. The sensitivity, positive predictive value and negative predictive value for ESAS were 66%, 56%, and 78%, and for FACIT-F were 52%, 81%, 76%, respectively. The correlation between global benefit score and change in ESAS was 0.57 [p<0.001], global benefit score and change in FACIT-F was 0.61 [p=0.001], and change in FACIT-F and change in ESAS was 0.62 [p≤0.001]. Conclusions: A difference in ≥ 4 in the ESAS and ≥ to 17 in the FACIT-F can be considered clinically significant in patients with cancer fatigue. The FACIT-F score showed higher specificity. Improvements in the FACIT-F score reported in clinical trials of fatigue are frequently not clinically significant. More research is needed to better characterize responder status in cancer fatigue.

No significant financial relationships to disclose.
A randomized trial of denosumab (AMG 162) versus intravenous (IV) bisphosphonates (BP) in cancer patients (pts) with bone metastases (BM) on established IV BP and evidence of elevated bone resorption
Authors: Suarez T. , Fizazi K. , Rahim Y. , Wilson J. , Fan M. , Jun S. , Lipton A.
Published: April 2020

8562

Background: Pts on established (≥ 8 weeks) IV BP who have elevated bone resorption markers, especially urinary N-telopeptide (uNTx), are at increased risk for skeletal related events (Coleman, J Clin Oncol 2005). Denosumab, a fully human monoclonal antibody, inhibits osteoclastic bone resorption by binding and neutralizing RANK ligand, a key mediator of osteoclast differentiation and function. Denosumab efficacy and safety were evaluated in a phase 2, randomized, open label, active-controlled study in advanced cancer pts with BM and elevated levels of uNTX despite established IV BP therapy. We report preliminary results from an interim analysis of 49 pts at week 13. Methods: Eligible pts (≥18 yrs old with solid tumor [except lung] or multiple myeloma [MM]; confirmed BM; screening uNTx > 50 nM BCE/mM creatinine [Cr]; on IV BP for ≥ 8 weeks before randomization) are stratified by baseline uNTx (50–100, >100) and tumor type. Pts are randomized to 1 of 3 arms: IV BP every 4 weeks (Q4W) or 180 mg denosumab given subcutaneously Q4W or Q12W. The primary endpoint is the proportion (%) of pts with uNTx < 50 nM BCE/mM Cr at week 13. Enrollment is ongoing (planned N = 135). Results: The mean (range) age of all pts in the analysis (33 denosumab; 16 BP) was 62.5 (39, 81) yrs; 96% had > 2 BM. The median time on prior IV BP (mostly zoledronic acid) was 5.1 months. Tumors included prostate (n = 24), breast (n = 20), other/MM (n = 5). The % of pts with uNTx < 50 nM BCE/mM Cr at week 13 was greater with denosumab (pooled arms) than IV BP: 76% (95% CI: 60.3, 91.2) vs 38% (95% CI: 18.5, 61.4; P = .015 Cochran-Mantel-Haenzel), respectively. No treatment-related serious adverse events (SAEs) were reported. Commonly reported AEs in the denosumab arms included nausea, peripheral edema, anemia, bone pain, and constipation. At data cutoff, 10 deaths (6/33 denosumab, 4/16 BP) had occurred on-study. Conclusions: These interim data suggest that denosumab normalizes uNTx more frequently than IV BP in pts with elevated uNTx despite 8 weeks of IV BP, across all tumor types. The AE profile of denosumab appeared similar to that of cancer pts undergoing treatment.

[Table: see text]
Long-term tolerability of fentanyl effervescent buccal tablets: Interim analysis in patients with cancer-related breakthrough pain
Authors: Slatkin N. , Charu V. , Niebler G. , Rauck R.
Published: April 2020

8567

Background: Fentanyl effervescent buccal tablets (FEBT) are designed to enhance the rate and efficiency of fentanyl absorption through the buccal mucosa. Results reported here represent a pre-specified interim analysis of an open-label safety and efficacy study of FEBT in opioid-tolerant patients with cancer-related breakthrough pain (BTP). Methods: Patients with cancer-related BTP receiving around-the-clock and supplemental opioids were eligible to enroll. Patients who had participated in a previous dose-titration study of FEBT enrolled directly into the 1-year phase; new patients entered a titration phase to determine an effective FEBT dose before entering the 1-year phase. An effective FEBT dose was defined as the dose needed to provide adequate analgesia for BTP. By October 3, 2005, 170 patients (aged 24 to 95 years) received FEBT (100–800 μg) and had documented safety data. Results: Of the 112 new patients, 70.5% identified an effective FEBT dose and were eligible for enrollment. In the long-term phase, patients received FEBT for a mean of 109.8 days; 8% at 100 μg, 15% at 200 μg, 23% at 400 μg, 25% at 600 μg, and 29% at 800 μg. The FEBT dose remained reasonably stable during the long-term phase, but 43 patients had a dose increase and 6 had a dose decrease at the discretion of the investigator. Only 2 patients required a change in the FEBT dose because of tolerability. The most common adverse events (AEs) are given in the table. The incidence of AEs did not correlate with the effective FEBT dose. The 42 patient deaths that occurred were all attributed to cancer-related pathology or the progression of cancer. Conclusions: Overall, FEBT was well tolerated in opioid-tolerant patients with cancer-related BTP.

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High prevalence of vitamin D deficiency in premenopausal women with early-stage breast cancer
Authors: Hershman D. L. , McMahon D. , Irani D. , Cucchiara G. , Crew K. , Raptis G. , Shane E.
Published: April 2020

8568

Background: The use of bisphosphonates in the treatment of breast cancer is increasing for patients with metastatic and early-stage disease. Vitamin D deficiency may be a risk factor for breast cancer development and is very common in the northeastern US. Vitamin D deficiency appears to increase the risk of hypocalcemia following IV bisphosphonate therapy. The purpose of this study is to evaluate the prevalence of vitamin D deficiency following the initial diagnosis of breast cancer. Methods: We analyzed fasting morning blood from premenopausal women, from the northeastern US, diagnosed with stage I/II breast cancer. Bloods were obtained following curative surgery, and prior to initiating therapy. Serum was archived, stored at -70o and analyzed in batches in a research laboratory for 25-hydroxyvitamin D (25-OHD; Diasorin RIA), albumin-corrected calcium, phosphate, parathyroid hormone (PTH), markers of bone turnover, FSH, LH, estradiol and sex hormone binding globulin (SHBG). Information on demographic, clinical and tumor characteristics were collected and bone mineral density (BMD) was measured (Hologic 4500). Data were analyzed using SAS version 9. Results: We analyzed sera from 36 premenopausal women, none of whom were taking calcium or vitamin D supplements. The mean age was 42 (range 27–54). The mean serum 25-OHD was 22.6 ng/dl, (SD 7.4) and similar among all racial/ethnic groups. Only 4 patients met contemporary criteria for optimal levels (>30 mg/ml); 18 patients had levels between 20–30 mg/ml, 14patients had “insufficient” levels (<20 mg/ml), and 3 patients had “deficient” levels (<12). Serum 25-OHD was inversely associated with serum PTH and free estradiol, and directly associated with SHBG. There were no associations between serum 25-OHD and serum calcium, phosphate, bone turnover markers, or BMD. Conclusions: Suboptimal vitamin D levels are surprisingly common among premenopausal women with early stage breast cancer. The associations between serum 25-OHD, SHBG and free estradiol, suggest that serum levels of vitamin D binding protein may be influencing 25-OHD measurements. Serum 25-OHD should be measured and low levels supplemented before initiating adjuvant bisphosphonate therapy, as vitamin D deficiency may increase the risk of hypocalcemia.

No significant financial relationships to disclose.
Direct decompressive surgery with post-operative radiotherapy (S + RT) versus radiotherapy (RT) alone for the treatment of metastatic epidural spinal cord compression (MESCC): A cost-utility analysis using Ontario health economic data
Authors: Chan K. K. , Furlan J. , Guillermo S. , Lam K. , Klinger C. , Fehlings M. G. , Patchell R. A. , Laporte A.
Published: April 2020

8570

Background: For selected patients with MESCC, S + RT has recently been shown to improve patients’ ability to ambulate and reduce opioid and corticosteroid use when compared with RT alone, with a trend towards survival benefit. (Patchell et al Lancet 2005) The economic impact of adopting this intervention has not been assessed previously. Methods: An analytic decision model was constructed based on the results from Patchell et al. (2005) The perspective of the public health care insurer of Ontario was adopted for the analysis. Costing was performed by using Ontario data for the following items: surgery, radiotherapy, hospitalization, home care services, palliative hospice, and medications. Utilities were obtained from the Harvard University Catalogue of preference score (HUC) and the Health Outcomes Data Repository Data - Health Utility list (HODaR). The primary analysis is a cost-utility analysis comparing surgery and radiotherapy (S+RT) with radiotherapy alone (RT). A probabilistic sensitivity analysis with Monte-Carlo simulation was performed. Results: When comparing S+ RT with RT alone, the incremental cost-effectiveness ratio (ICER) is CAD$ 43,796 per QALY gained. The cost-utility of S + RT is CAD$ 509,084 per QALY and that of RT alone is CAD$ 2,381,246 per QALY. S + RT costs approximately CAD$ 33 more when compared with RT alone per ambulatory day gained. The cost of surgery is partially offset by the decreased cost of hospice palliative care since more patients remain ambulatory and stay at home. Monte-Carlo simulation showed that there is a 25% chance that S + RT may dominate RT alone. The results are sensitive but generally robust to changes in assumptions about the costs of surgery, home care and palliative hospice care. Conclusions: S+RT is likely cost-effective when compared with RT alone for the treatment of MESCC in selected patients, and should be considered by health care policy makers.

No significant financial relationships to disclose.
Symptom prevalence of cancer patients dying with and without palliative sedation at a specialized unit for palliative care in a cancer center
Authors: Van Zuylen L. , Van der Wijk L. , Van Veluw H. , Van der Heide A. , Van der Rijt C. C.
Published: April 2020

8576

Background: Palliative sedation (PS) may be needed in dying cancer patients to achieve acceptable symptom control. Little is known about the differences between sedated and non-sedated patients. To determine characteristics of sedated and non-sedated patients, we performed a retrospective study in patients who died during admission to the palliative care unit (PCU) of the cancer center. Methods: From October 2001 until October 2005, 157 out of 753 admitted patients died at the PCU. The medical and nursing records were studied with respect to patient characteristics and the symptom profile at admission and during the last 72 hrs of life. Results: Of all deceased patients, 68 (43%) were sedated prior to death. The median duration of the sedation was 19 hrs (range 0.7–125). No differences between sedated and non-sedated patients were found in age (median 58 years, range 25–89) and time between admission and death (7 days, 1–38). The primary tumor sites were mostly lung (22.1%), GI tract (20.6%), and breast (16.2%) in the sedated patients, and breast (24.7%), lung (13.5%) and urogenital tract (11.2%) in the non-sedated patients. The symptoms at admission were mainly pain (82%), constipation (43%) and dyspnea (31%) and did not differ between both groups. Prior to the start of PS, sedated patients more often had delirium and dyspnea as compared to non-sedated patients at similar times before death. Conclusions: PS was needed to control symptoms for somewhat less than half of the patients dying at the PCU. Pain was a main reason for admission in both groups, but dyspnea and delirium were more common in sedated patients during admission.

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No significant financial relationships to disclose.
Validation of single item Linear Analogue Scale Assessments (LASAs) for assessing quality of life (QOL) in patients with newly diagnosed high-grade gliomas
Authors: Decker P. A. , Ballman K. V. , Locke D. E. , Brown P. D. , Jaeckle K. A. , Buckner J. C. , Rummans T. A. , Clark M. M. , Sloan J. A.
Published: April 2020

8583

Background: Patient QOL assessment requires balancing the detail provided by multi-item assessments with the reduced burden of single-item assessments. We investigated the psychometric properties of single-item LASA assessments used in 3 North Central Cancer Treatment Group (NCCTG) phase II trials for patients with newly diagnosed high-grade gliomas. Methods: Measures included QOL LASAs (overall, physical, emotional, spiritual, intellectual), Symptom Distress Scale (SDS), Profile of Mood States (POMS), and Functional Assessment for Cancer Therapy (FACT; overall, physical, emotional). Association of LASA measures with SDS, POMS, and FACT domains and with ECOG performance score (PS) and MMSE was assessed with Spearman’s correlation. Repeated measures ANOVA models compared the change over time of LASAs and SDS, POMS, and FACT. Cox regression modeled the association of baseline QOL and survival. Results: 205 patients completed the QOL assessments across 3 time points. LASA mean scores ranged from 60–78; SDS, POMS, and FACT ranged from 68–81. No significant changes across time for overall and emotional scores were observed. FACT physical decreased over time (p<0.001) as did LASA physical (p=0.08). LASA scales were strongly associated with corresponding scales on SDS, POMS, and FACT (0.44<rho<0.65; p<0.001). LASA was negatively associated with PS and positively with MMSE. Baseline scores for overall FACT (p=0.005) and LASA physical (p=0.015) were associated with better survival. Conclusions: The single-item LASA assessments have comparable psychometric properties as longer assessments for the same constructs. Correlations with PS and MMSE were as expected (convergent/concurrent validity). The discriminant validity and prognostic ability of LASA items were similar to the multi-item instruments. Collectively, the data suggest that the single item LASA scales are valid for assessing QOL in patients with newly diagnosed high grade gliomas and are an appropriate alternative when a shorter instrument is warranted.

No significant financial relationships to disclose.
L-carnitine supplementation improves fatigue, mood and sleep in cancer patients with fatigue and carnitine deficiency
Authors: Cruciani R. A. , Dvorkin E. , Homel P. , Culliney B. , Malamud S. , Shaiova L. , Lapin J. , Blum R. H. , Lesage P. , Portenoy R. K. , Esteban-Cruciani N. V.
Published: April 2020

8588

Background: Carnitine is a natural aminoacid derivative that plays a crucial role in cellular energy metabolism. To determine the dose and tolerability we conducted a phase II study with increasing doses of L-carnitine supplementation. In a preliminary analysis, we reported that L-carnitine could improve fatigue, mood and sleep. (Cruciani et al., 2004). Analysis of the full dataset has confirmed and extended these findings. Methods: Patients had active cancer, fatigue and a Karnofsky ≥50. Carnitine deficiency was defined as free carnitine <35 μm]/L for males and <25 for females (normal range 35–67 and 25–55 respectively), or a ratio of acyl/free carnitine >0.4. We utilized a standard maximum tolerated dose (MTD) design, with 3 patients assigned to each successive dose group, starting at 250 mg/day and increasing in each group by 500 mg/day to a maximum dose target of 3000 mg/day. Fatigue (measured by the BFI), depressed mood (CES-D), quality of sleep (ESS), and performance status (Karnofsky), as well as carnitine serum levels were assessed at baseline and after one week of L-carnitine supplementation. Results: Seven groups of three patients each received L-carnitine supplementation for a week with 250, 750, 1,250, 1,750, 2,250, 2,750 or 3,000 mg/day. Of the 27 patients accrued 21 completed the study. Of these, 17 (mean (SD) age = 63.0 (18), females=8) showed an increase in serum L-carnitine levels. The median (min, max) total carnitine increased from 31 (21, 68) to 51 (29, 111) (p < 0.001) and the free carnitine increased from 25.0 (17, 48) to 39 (25, 82) (p < 0.001). The median (min, max) BFI score at baseline was 63 (36, 81) versus 39 (8, 82) after one week (p<0.001). There was also a significant dose response for BFI (r = -0.61, p = 0.01). Median (min, max) CES-D at baseline was 31. (4, 48) and 18.0 (0, 40) after one-week (p = 0.001). Median (min, max) ESS at baseline was 13.7 (2, 22) and 10.3 (1, 18) after one week (p=0.003). Median Karnofsky score did not change (pre and post = 70). Side effects were not observed in any of the groups. Conclusions: This study suggests that L-carnitine is safe up to 3,000 mg/day. Supplementation was associated with improvements in fatigue and depression scores. Fatigue improved in a dose dependent manner.

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Development of the functional capacity screening tool (FCST): A brief instrument to identify functional capacity deficits in anemic cancer patients
Authors: Cella D. , Viswanathan H. , Hays R. D. , Mendoza T. , Stein K. , Pasta D. , Potter L. , Vadhan-Raj S. , Kallich J.
Published: April 2020

8593

Background: Existing fatigue measures are long and often difficult to incorporate in practice. The objective of this study was to develop a short tool (Functional Capacity Screening Tool [FCST]) to identify functional capacity deficits related to fatigue in anemic cancer patients (pts) using self-report and performance-based measures of functional capacity. Methods: Data were obtained from a multicenter, open-label, single-arm study of darbepoetin alfa therapy (3.0 μg/kg every 2 weeks) in cancer pts (n=1558) who were ≥ 18 years of age with nonmyeloid malignancies receiving cyclic chemotherapy and anemia (hemoglobin [Hb] ≤ 11 g/dL). The Modified Harvard Step Test (MHST) was used as a performance-based measure of functional capacity to assess adjusted VO2max. Pts who contributed data for the development of FCST completed the following: MHST, baseline and ≥ 1 follow-up Hb measurement, baseline and ≥ 1 follow-up Functional Assessment of Cancer Therapy-Fatigue (FACT-F), and fatigue assessed within 3 days of MHST. Items from FACT-F, Brief Fatigue Inventory (BFI), Fatigue Symptom Inventory (FSI) and Medical Outcomes Study physical functioning scale were tested for inclusion in the FCST. Individual item scores were transformed to a 100-point scale. Item selection was based on identifying best predictors of adjusted VO2max, Hb, and global FACT-F scores using linear regression and the r-square selection method. FCST scores were calculated by summating item scores and dividing by number of items. Results: Data from401 pts contributed to the development of the FCST. Eight items were identified for the FCST with a Cronbach’s coefficient alpha of 0.92. Construct validity was supported by correlations of FCST with FSI (r = 0.80, P < .0001) and BFI (r = 0.86, P < .0001). Correlations between FCST and energy (r = 0.75, P < .0001), productivity (r = 0.72, P < .0001), and Hb (r = 0.24, P < .0001) further supported construct validity. Conclusions: FCST holds promise as a short screening tool for identifying functional capacity deficits in cancer pts. This new instrument was reliable, easy to score, and completed quickly by pts, making it suitable for incorporation in clinical practice. Further validation is required in different cancer populations.

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A population-based study on the quality of life for cancer patients as reported in a tumor registry follow-up
Authors: Novotny P. J. , Sloan J. A. , Frost M. , Harris M. , Huntington J. , Chute C. , Clement-Brown K.
Published: April 2020

8594

Background: Between 1/96 and 3/00, 94,516 SF-36 or SF-12 Quality of Life (QOL) forms were sent to every patient on the Mayo Clinic tumor registry not seen at the clinic in the last year. This study is a descriptive summary of each patient’s first reported QOL score. Method: QOL scores were combined with tumor registry information about age, gender, tumor site, tumor stage, residence, and date of diagnosis. Responder versus non-responder characteristics were compared via Fisher’s exact tests and two-sample t-tests. Means and standard deviations were used to summarize the data. Patient reported scores and SF norms from a healthy population were compared using one sample t-tests. Results: Data were available on 28,166 patients (48,463 forms). Men were more likely to respond. More patients were male (56%) with a mean age of 66 and filled out their first SF form an average of 9 years after their initial diagnosis. Overall, mean physical and mental subscale scores were not clinically different from the age- and sex-adjusted SF normative data (Table). Within tumor sites, mental subscale scores were similar to the general population. Physical subscale scores were also approximately normal within each of the tumor sites. The exceptions were that patients with lung or musculoskeletal cancers tended to report lower physical scores than a healthy population. Conclusions: Patients responding to a tumor registry follow-up program reported QOL scores that were not clinically different from that of a healthy population. QOL deficits observed in patients with lung cancer and musculoskeletal cancers may indicate a need for targeted interventions specific for these cancer patient populations.

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No significant financial relationships to disclose.
Pegfilgrastim (N) induced bone pain (NIBP): Incidence, risk factors and management in a community practice
Authors: Kirshner J. J.
Published: April 2020

8598

Background: In the early clinical trials, the incidence of NIBP was 15–30%, with ‘severe‘ pain in less than 8% of patients (pts). The incidence in clinical practice may be higher and contribute to a significant decrease in quality of life (QOL) for pts undergoing chemotherapy(Ch). Methods: In our large oncology practice (HOACNY), pts were surveyed following their initial injection of N. Pain was graded on a scale of 1–10. Pts were divided into 3 groups: no pain (1), pain 1–5 (2) and pain 6–10(3). Pts recorded the day of onset, duration of pain and its location. Information was obtained as to how the pts treated their pain and how effective the treatment was.Data was collected re: age, sex, disease,and Ch and whether pts were already on analgesics/steroids. All pts received 10–20 mg of IV dexamethasone pre-Ch. N was administered 24–72 h post chemotherapy. Differences among the groups were analyzed using the t-test. Results: To date, surveys have been analyzed from 75 pts, with results tabulated below. Dose dense AC for adjuvant breast ca was the most common Ch (44%). There were no significant differences among the groups when analyzed by pt age, sex, disease, or Ch, although there was a higher % of lung ca pts in Gp 3 (treated with carboplatin/paclitaxel). On average, the onset of pain was within the first 2 days & lasted 2–3 days(Gp2) and an additional day (Gp 3). Gp 2 pts had more localized pain than Gp 3 pts & responded very well to APAP or NSAID’s. Gp 3 pts had more diffuse pain and 50% had minimal or no relief with OTC analgesics. Conclusions: NIBP is a significant problem in clinical practice, interfering with pt QOL. It is unpredictable and often severe & may be refractory to OTC analgesia. It may be more common in lung ca pts treated with carboplatin/paclitaxel. A prospective randomized trial is planned (URCC CCOP Research Base) to further define the problem and determine if daily ‘premedication‘ with NSAIDS could reduce or eliminate NIBP.

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Eltrombopag, a novel, oral platelet growth factor, increases platelet counts in thrombocytopenic patients and healthy subjects
Authors: Bussel J. , Saleh M. , Provan D. , Stone N. , Hamilton J. M. , Hassani H. , Mayer B. , Uhl J. , Jenkins J. , Glaspy J.
Published: April 2020

8602

Background: Eltrombopag (SB-497115) is a novel, first in class, orally bioavailable, thrombopoietin receptor agonist that induces differentiation and proliferation of megakaryocyte progenitors and has been shown to increase platelet counts in preclinical and clinical studies. Methods: In two randomized, placebo-controlled trials, eltrombopag was administered as oral tablets, once daily for 10 days to 73 healthy male subjects at doses of 5–75mg in an ascending dose cohort study, and to 103 (64 female/39 male) adult chronic immune thrombocytopenic purpura (ITP) patients, with a platelet count of <30×109/L, once daily for 6 weeks at doses of 30–75mg in a parallel dose cohort study. The primary efficacy endpoint in the Phase II ITP trial was the proportion of subjects with a platelet count >50×109/L after 6 weeks of dosing. Results: In healthy subjects, eltrombopag induced a dose dependent increase in the platelet counts. Mean maximal platelet count increases were 24.1 % at 30mg, 42.9 % at 50mg, and 50.4 % at 75mg. In 95 eligible ITP patients, platelet counts increased from <30 to >50×109/L in 16% (4/25) of subjects on placebo, and in the eltrombopag groups in 28% (7/25, p=ns) on 30mg, 67% (16/24, p<0.001) on 50mg and 86% (18/21, p<0.001) on 75mg eltrombopag. The median platelet counts in each treatment arm after 6 weeks of dosing were 16×109/L on placebo, 29×109/L on 30mg, 132×109L on 50mg, and 202×109/L on 75mg. The dose dependent effect was not significantly affected by the splenectomy status, background immunosuppressant use, or baseline platelet count (greater than or less than 15×109/L). Conclusions: The platelet count data from these clinical studies suggests that eltrombopag could be an effective therapy for the treatment of thrombocytopenia. Eltrombopag is being tested in further studies involving patients with ITP and chronic liver disease, and cancer patients receiving thrombocytopenic chemotherapy.

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Renal insufficiency in cancer patients: Prevalence and implications on anticancer drugs management. Results of the IRMA study
Authors: Launay-Vacher V. , Oudard S. , Janus N. , Le Tourneau C. , Rixe O. , Pourrat X. , Gligorov J. , Beuzeboc P. , Deray G. , Morere J.
Published: April 2020

8603

Background: Patients with abnormal renal function are at high-risk for drug-induced nephrotoxicity. Furthermore, near half anticancer drugs are predominantly excreted in urine and dosage adjustment in RI is therefore a crucial issue. In 2005, the IRMA study (Insuffisance Rénale et Médicaments Anticancéreux) thus investigated the prevalence of RI in cancer patients and the profile of anticancer drugs prescribed. Methods: Data were collected for cancer patients presenting at one of the 14 IRMA centers in February 1st-15th or October 1st-15th, 2004: type of tumour, sex, age, weight, serum creatinine (SCR), haemoglobinemia, anticancer drugs. Dialysis and myeloma patients were not included. The prevalence of SCR>110 μmol/L was assessed. GFR was estimated with the Cockcroft-Gault (CG) and the abbreviated MDRD (aMDRD) formulae and patients were classified according to their K/DOQI stage of RI (Table). Anticancer drugs necessitating dosage adjustment and those potentially nephrotoxic were identified. Results: 4,684 patients (Breast, 1,898; Colorectal, 573; Lung, 445; Ovarian, 270; Prostate, 222) were included: mean age 58.1 years, weight 65.8 kg, sex-ratio 0.55. The prevalence of elevated SCR was 7.2% and those of GFR <90 ml/min was 57.4% with CG and 52.9% with aMDRD. 53.4% of the 7181 prescriptions needed dosage adjustment and 79.9% of treated patients (n=3823) were receiving at least one drug needing dosage adjustment. 53.3% of prescriptions were potentially nephrotoxic and 80.1% of treated patients received at least one nephrotoxic drug. 46.8% had a serum haemoglobin lower than 12 g/dL and still 25.9% were lower than 11 g/dL. Conclusions: The results of the IRMA study showed that RI is highly frequent in cancer patients and that 80% of the patients receive potentially nephrotoxic drugs and/or for which dosage must be adjusted in RI. Furthermore in IRMA patients, anemia was still highly frequent.

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No significant financial relationships to disclose.
A prediction model for chemotherapy-associated thrombocytopenia in cancer patients
Authors: Kuderer N. M. , Francis C. W. , Crawford J. , Dale D. C. , Wolff D. A. , Culakova E. , Poniewierski M. S. , Lyman G. H.
Published: April 2020

8616

Background: Thrombocytopenia (TP) can lead to serious complications, however, little is known about the incidence and risk factors for chemotherapy-associated TP. A prospective, nationwide cohort study was undertaken to better define the impact of TP in cancer treatment. Methods: 2,842 patients with cancer of the breast, lung, colon, ovary or lymphoma initiating a new chemotherapy regimen have been prospectively enrolled at 115 randomly selected US community oncology practices between 2002 and 2005. Risk factors for chemotherapy-associated TP were identified, a multivariate logistic regression model based on pretreatment characteristics was developed, and test performance characteristics were estimated. Results: Over a median of 3 cycles of chemotherapy, minimum recorded platelet counts were: ≥150K in 53% of patients; 100–150K in 26%; 75–100K in 8%; 50–75K in 6% and <50K in 7%. Significant independent predictive factors for platelets <75K include type of cancer (P<.0001), type of chemotherapy including gemcitabine-based (P<.0001), anthracycline-based (P<.0001) and platinum-based (P<.0001) regimens, prior chemotherapy (P<.0001) or surgery (P=.005), age (P=.015), Caucasian ethnicity (P=.022), body surface area (P=.0001), planned relative dose intensity ≥85% (P=.082), diabetes (P=.018), pulmonary disease (P=.011), abnormal baseline platelets (P<.0001), hematocrit (P=0.030), alkaline phosphatase (P=.072) or albumin (P=.017). Model fit was good (Chi-square, P<.0001), R2 = 0.735 and c-statistic = 0.816 [95% CI: 0.792–0.840, P<.0001]. Model test performance characteristics [95% CI] at a ≥20% risk of TP include: sensitivity 56% [51–61]; specificity 88% [87–89]; likelihood ratio positive 4.63 [4.02–5.33]; likelihood ratio negative 0.50 [0.45–0.57]; and diagnostic odds ratio 9.22 [7.23–11.75]. Validation of the model is underway. Conclusions: This prediction model based on pretreatment factors identifies with high specificity patients at risk for clinically important chemotherapy-associated thrombocytopenia early in the treatment course. It may provide a valuable tool for guiding chemotherapy and new supportive care measures.

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Switching from methadone to a different opioid: What is the equianalgesic dose ratio?
Authors: Walker P. W. , Bruera E. , Pei B. , Kaur G. , Zhang K. , Jeanine H. , Curry E. , Palla S. , Mansell M.
Published: April 2020

8617

Background: Methadone (ME) is a highly effective opioid agonist used for difficult pain syndromes. However, the rotation from ME to another opioid may be difficult because of the absence of a uniformly accepted conversion ratio. Methods: We retrospectively reviewed consecutive medical records of Pts undergoing an opioid rotation from ME to an alternative opioid. For inclusion, Pts were required to have received ME for at least 3 days prior to the switch and reach a stable dose of the alternative opioid(s) during 7 days following. Stable dose was defined as a 30% or less change in opioid dose from one day to the next. For purposes of analysis, on the day before the switch, doses, were divided into ME doses and the oral morphine equivalent daily dose (MEDD), based on medication and route of all other opioids taken on that day, using standard equinalgesic tables. All doses after the switch were converted to the MEDD. For Pts receiving ME and a second opioid prior to the switch, the MEDD of the second opioid was subtracted from the MEDD calculated for the day when stable dose was reached. The remainder was used to calculate the equianalgesic raio with the previous ME dose. Results: Records on 39 Pts met inclusion criteria. Excluded from analysis were 5 Pts who were restarted on ME in < 8 days, 2 whose opioid dose markedly decreased of post switch, and 3 due to concerns about reliability of multiple routes used for fentanyl. Data from 29 Pts, 10 female, mean age 48 ±14.4 were evaluable. The ratio for: oral ME to MEDD was 1:4.7 (CL 3.0–6.5)(n=16), IV ME to MEDD was 1:13.5 (CL6.6–20.5)(n=13), p=0.06. ME dose is significantly correlated to stable MEDD after switching opioids for both ME IV and oral (Spearman=0.86,p=0.0001 and Spearman=0.72, p=0.0024, respectively. Mean day of achieving stable dose was on day 2.5 ±0.2 for IV ME and day 2.6±0.3 for oral ME. Conclusions: These dose ratios are new findings that will assist in switching Pts more safely to alternative opioids, when side effects or pain problems occur.An important difference in analgesic potency appears to exist between IV and oral ME. Further research with prospective studies is required.

No significant financial relationships to disclose.
Adherence to prescribed oral medications: Understanding the barriers to optimizing hormonal therapy in breast cancer (BC)
Authors: Kirk M. , Hudis C.
Published: April 2020

8621

Background: Several studies have demonstrated suboptimal adherence to oral anticancer agents. Understanding barriers to treatment adherence is increasingly important with the growing number of oral agents available to treat BC. Gaining insights into the attitudes and behaviors of patients (pts) with BC regarding their prescribed treatment is necessary to identify and address factors responsible for poor adherence with oral medications. Methods: To identify barriers to adherence with oral hormonal medications, a self-reported, 30-question internet survey was posted on www.y-me.org from June 30 through October 31, 2005. Results: Of the 328 survey respondents, 65.9% were diagnosed with early BC and 53.3% were postmenopausal. Of the 60% of pts with BC who had been prescribed an oral therapy, 44.6% were prescribed tamoxifen, 31.8% anastrozole, and 7.9% letrozole. 88.6% of patients indicated that their healthcare provider discussed the importance of taking oral medications as directed. Only 44.2% reported receiving instruction on the importance of taking oral medications as directed at every office visit. For 33.3%, this topic was reportedly discussed only once, prior to treatment. 83.6% of patients indicated they were taking their oral therapy as directed, but only 57.4% rated their ability to adhere to therapy (not missing a single dose) as excellent. For 35.5%, knowing that adherence may improve clinical outcome would help them take their oral medication as directed. For 24.1%, better management of treatment-related side effects would improve their adherence to therapy. Conclusions: To improve adherence, the results of this survey suggest that healthcare professionals should discuss and emphasize 1) the importance of taking oral medications as directed and 2) the impact of adherence on clinical outcomes. Greater attention to managing treatment-related side effects may further enhance adherence to therapy.

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Relative efficacy of various 5- hydroxytryptamine receptor antagonists in the prevention and control of acute nausea and vomiting associated with platinum-based chemotherapy
Authors: Hamadani M. , Padmanabhan R. , Chaudhary L. , Tfayli A.
Published: April 2020

8623

Background: The introduction of 5-Hydroxytryptamine-3 receptor (5-HT3) antagonists has represented a significant clinical advance in the prevention and treatment of chemotherapy-induced nausea and vomiting (CINV), particularly for patients receiving highly emetogenic platinum-based regimens. However no study to date has compared the relative efficacy of Dolasetron, Granisetron, Ondansetron and Palonosetron with Dexamethasone in the prevention and control of acute CINV in patients undergoing platinum-based therapy. Methods: Retrospective data were reviewed for 207 consecutive patients receiving Platinum-based chemotherapy in our infusion center between November 1999 and August 2005. Patients receiving 5-HT3 antagonists without Dexamethasone (n=11) were not eligible for the study. Further 15 patients were excluded because of no documentation of CINV. The remaining 181 patients constitute the subject of this study. Patient characteristics including age, sex, race, diagnosis, history of heavy alcohol intake, chemotherapy regimen administered, number of cycles, and performance status at the start of therapy were noted. Primary outcome measure was complete control of acute CINV. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. Results: The 181 patients received 572 cycles of platinum-based therapy. Dolasetron (n=157), Granisetron (n=81), Ondansetron (n=131) and Palonosetron (n=203) (each given with Dexamethasone) achieved complete control of vomiting in 89.8%, 95.5%, 92.3% and 88.1% (ρ=0.86) of cycles respectively. Respectively, complete nausea control was observed in 68.1%, 75.3%, 69.4% and 73.3% (ρ=0.35). DEX 20 mg was not superior to 10mg in complete control of nausea and vomiting (ρ=0.06 and ρ=0.67 respectively). Similarly complete control of nausea and vomiting (ρ=0.12 and ρ=0.10 respectively) was not significantly different in patients getting cisplatin compared to carboplatin based regimens. Conclusion: This study does not demonstrate a significant difference in the efficacy of the four 5-HT3 antagonists in controlling acute CINV. The higher dose of Dexamethasone confers no added benefit over the lower 10mg dose.

No significant financial relationships to disclose.
Final results of a randomized study comparing two dosing regimens of epoetin alfa in patients with chemotherapy-induced anemia: 80,000 U every two weeks vs 40,000 U weekly
Authors: Henry D. H. , Kamin M. , Wilhelm F. , Williams D. , Xie J. , Woodman R. C.
Published: April 2020

8624

Background: Epoetin alfa is typically administered weekly (QW) for the treatment of chemotherapy (CT)-induced anemia. Less frequent dosing can be more convenient for patients (pts) and healthcare providers. This is the first study to examine extended interval initial dosing with epoetin alfa 80,000 U every two weeks (Q2W) vs the standard 40,000 U QW regimen. Methods: This randomized, open-label, 13-week study enrolled pts with non-myeloid malignancies with baseline (BL) hemoglobin (Hb) ≤ 11 g/dL and CT planned for ≥ 12 weeks. Pts were assigned (1:1) to receive epoetin alfa 40,000 U QW or 80,000 U Q2W subcutaneously. Drug was held for Hb > 13 g/dL and dose was reduced for Hb > 12 g/dL or rate of rise > 1 g/dL in any 2-week period. For inadequate Hb response, 80,000 U Q2W pts were switched to 40,000 U QW and 40,000 U QW patients were increased to 60,000 U QW. The primary analysis was a comparison of the mean Hb change from BL to end of study (EOS). Results: 298 pts received ≥ 1 dose of drug (153 Q2W, 145 QW). BL characteristics were comparable between groups: 66% female, overall mean age 62 yrs, and BL Hb 10.0 g/dL. Most common tumor types were breast (25%), NSCLC (15%) and colorectal (14%). Efficacy was analyzed in 295 pts (151 Q2W, 144 QW) who had ≥ 1 post-BL Hb value. The mean Hb change from BL to EOS for Q2W was 1.27 ± 1.48 g/dL compared to 1.28 ± 1.60 g/dL for QW [difference 0, 1-sided 95% CI -0.25,–]. In the per protocol population, the difference in mean Hb change was similar. Mean Hb values over time were also similar between groups. Kaplan-Meier estimates of post-28 day transfusion rates were 11.2% in Q2W vs. 12.0% in QW. Fewer Q2W pts compared to QW pts required dose holds (21% vs 42%) or dose reductions (41% vs 59%). 13% of Q2W pts were switched to QW dosing and 37% of QW pts required a dose increase. The incidences of clinically relevant TVEs and deaths were similar in the Q2W vs QW groups (7.8% vs 7.6% and 6.5% vs 6.2%, respectively). Conclusions: Pts treated with epoetin alfa 80,000 U Q2W demonstrated similar Hb increases, transfusion rates, and safety outcomes compared to pts treated with 40,000 U QW. Epoetin alfa 80,000 U every other week is an effective regimen that may provide a more convenient dosing option for pts with CT-induced anemia.

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Patient wishes and physician inquiries regarding spiritual needs in an urban cancer center
Authors: Astrow A. B. , Wexler A. , Texeira K. , Sulmasy D. P.
Published: April 2020

8630

Background: Prior studies have shown much interest in spirituality among patients in the rural South, but little is known about the spiritual needs and views of urban cancer patients. Methods: In Jan-Feb 2005, consecutive outpatients were asked to complete a questionnaire at the St. Vincent’s Comprehensive Cancer Center in New York City. The instrument included the QUEST satisfaction scale, demographic and clinical information, and questions about spiritual and religious beliefs and needs. Tests of association included correlation, t-tests, and χ2. Multivariate models were estimated using logistic techniques. Results: Of the 891 eligible patients, 81 refused, 428 cancelled their appointments or left before being approached. 13 were excluded because of incomplete questionnaires. The 369 participants had a mean age of 57.5 years; 65% were women, 67% white, 65% college-educated, 32% had breast cancer, and 67% were privately insured. Forty-seven percent were Catholic, 19% Jewish, 16% Protestant, and 6% atheist or agnostic. Sixty-six percent reported being “spiritual but not religious,” and 29% attended religious services at least once per week. Nine percent reported that staff had inquired about their spiritual or religious beliefs (0.6% by an MD), and 6% reported inquiries about their spiritual needs (0.9% by an MD). But, 82% reported that their spiritual needs were being met, and being asked about neither religious beliefs (p = .37) nor spiritual needs (p = .72) was associated with satisfaction. Still, 52% thought it appropriate for physicians to inquire about their religious beliefs and 58% thought it appropriate for physicians to inquire about their spiritual needs. Patients who described themselves as “spiritual but not religious” were less likely to think it appropriate for an MD to inquire about their religious beliefs (OR = 0.48, CI = 0.28 to 0.84), while those who attended religious services at least weekly were more likely to think it appropriate (OR = 2.86, CI = 1.45 to 5.62). Conclusions: A majority of patients thought it appropriate to be asked about their spiritual and religious beliefs and needs, but less than that reported in other settings. Few had these needs addressed by staff, especially by MDs. More religious patients were more likely to think such inquiries appropriate.

No significant financial relationships to disclose.