Seisler, Drew K.

Background Lymphedema is an adverse effect of breast cancer treatment that causes swelling and pain in the arm and hand. We tested 2 lymphedema prevention interventions and their impact on health‐related quality of life (HRQOL) in a group‐randomized trial at 38 cooperative group sites within the United States. Methods Patients were recruited before breast surgery. Sites were randomly assigned to education‐only (EO) lymphedema prevention or education plus exercise and physical therapy (LEAP). Lymphedema was defined as a ≥10% difference in arm volume at any time from baseline to 18 months postsurgery. HRQOL was assessed using the Functional Assessment of Cancer Therapy–Breast plus 4 lymphedema items (FACT‐B+4). Longitudinal mixed model regression analysis, adjusting for key demographic and clinical variables, examined participants' HRQOL by intervention group and lymphedema status. Results A total of 547 patients (56% LEAP) were enrolled and completed HRQOL assessments. The results revealed no differences between the interventions in preventing lymphedema ( P = .37) or HRQOL (FACT‐B+4 total score; P = .8777). At 18 months, the presence of lymphedema was associated with HRQOL at borderline significance ( P = .0825). However, African American patients reported greater lymphedema symptoms ( P = .0002) and better emotional functioning ( P = .0335) than patients of other races or ethnicities. Lower HRQOL during the intervention was associated with younger age ( P ≤ .0001), Eastern Cooperative Oncology Group performance status >0 ( P = .0002), ≥1 positive lymph nodes ( P = .0009), having no education beyond high school ( P < .0001), having undergone chemotherapy ( P = .0242), and having had only axillary node dissection or sentinel node biopsy versus both ( P = .0007). Conclusion The tested interventions did not differ in preventing lymphedema or in HRQOL outcomes. African American women reported greater HRQOL impacts due to lymphedema symptoms than women of other races or ethnicities.

Background Lymphedema affects many women who are treated for breast cancer. We examined the effectiveness of an education‐only (EO) versus education plus sleeve compression/exercise intervention (lymphedema education and prevention [LEAP]) on lymphedema incidence and range of motion (ROM) in a group‐randomized trial across 38 cooperative group sites. Methods The treating institution was randomly assigned to either EO or LEAP by a study statistician. All patients at a treating institution participated in the same intervention (EO or LEAP) to minimize contamination bias. Participants completed surveys, arm volume measurements, and self‐reported ROM assessments before surgery and at 12 and 18 months after surgery. Lymphedema was defined as a ≥10% difference in limb volume at any time post‐surgery up to 18 months after surgery or diagnosis by a health provider. Cochran‐Mantel‐Haenszel tests were used to compare lymphedema‐free rates between groups, stratified by lymph node surgery type. Self‐reported ROM differences were compared between groups. Results A total of 554 participants (56% LEAP) were included in the analyses. At 18 months, lymphedema‐free rates were 58% (EO) versus 55% (LEAP) ( P = .37). ROM for both arms was greater in LEAP versus EO at 12 months; by 18 months, most women reported full ROM, regardless of group. In LEAP, only one‐third wore a sleeve ≥75% of the time; 50% performed lymphedema exercises at least weekly. Conclusion Lymphedema incidence did not differ by intervention group at 18 months. Poor adherence in the LEAP group may have contributed. However, physical therapy may speed recovery of ROM. Further research is needed to effectively reduce the incidence and severity of lymphedema in patients who have breast cancer.

e20605 Background: Intravenous (IV) fosaprepitant is a potent antiemetic, commonly used in patients receiving chemotherapy. The purpose of this study was to investigate the incidence of IV fosaprepitant-associated infusion site adverse events (ISAEs) among a cohort of breast cancer patients receiving doxorubicin and cyclophosphamide (AC) chemotherapy at Mayo Rochester. Methods: A retrospective review of electronic medical record (EMR) data was performed for all patients who were initiated on AC chemotherapy from January 2011 to April 2012. Data collected from the EMR included baseline demographics, antiemetic regimen, documentation of ISAEs and type of IV access (peripheral vs. central). Descriptive statistics (mean and standard deviation or percentages) were summarized overall and by type of IV access and initially administered antiemetic. Results: 148 patients were included, with a median age of 54 years (range 28-76). 98 patients initially received IV fosaprepitant; 44 oral aprepitant; 6 neither. 132 (89%) initially had peripheral IV access and 16 (11%) had central venous access. Overall, 33 patients (34%) experienced an IV fosaprepitant associated ISAE including: erythema (n=22), pain (n=26), swelling (n=12), infusion site hives (n=5), extravasation (n=4), deep venous thrombosis (n=3), superficial thrombosis (n=7), phlebitis/thrombophlebitis (n=5), venous discoloration (n=1), venous engorgement (n=1), venous hardening/induration (n=4) and local scarring (n=1). Only 1 patient (2%) experienced an oral aprepitant associated ISAE, which was infusion site pain. This patient had previously had a fosaprepitant associated ISAE at the same site. All experienced ISAEs occurred in patients with peripheral IV access. Conclusions: The incidence and severity of ISAEs associated with IV fosaprepitant administration among a group of patients receiving doxorubicin/cyclophosphamide chemotherapy is significant and is appreciably higher than what has been noted in other reports. The higher incidence observed is likely related to the predominance of peripheral venous access used in the studied cohort.

e17538 Background: Adherence to guideline-consistent chemotherapy-induced nausea and vomiting (CINV) prophylaxis is suboptimal. The primary aim of this study was to evaluate the magnitude of compliance to institutional guideline-directed antiemetic prophylaxis using a computerized physician order entry system at a single tertiary care institution. A nurse survey was also performed to evaluate how oncology practices, within a cooperative group, manage clinician orders for the prevention of CINV. Methods: The electronic medical records of 100 consecutive patients were evaluated. The primary endpoint was the incidence of compliance to provide all aspects of institutional guideline-directed antiemetic prophylaxis for acute (Day 1) and delayed (Days 2-4) CINV for patients receiving high, moderate, low, and minimally-emetogenic chemotherapy (HEC/MEC/LEC/MinEC). Noncompliance was declared if a recommended antiemetic was not prescribed per the guidelines or if additional antiemetics were prescribed. Descriptive analyses were performed on the convenience sample. Logistic regression was applied to determine the association of potential factors with noncompliance. Results: The incidence of compliance on Days 1-4 was 94%. Half of the noncompliant events occurred on Day 1 alone and involved the omission of pre-chemotherapy prochlorperazine in patients receiving LEC (3 of 6, 50%). There was a high-degree of compliance to institutional guidelines for delayed CINV (97%). Patients receiving doxorubicin/cyclophosphamide were numerically less likely to receive institutional guideline-directed antiemetic prophylaxis, compared to patients receiving other chemotherapy regimens (OR: 0.24 (0.04, 1.36), p-value: 0.05). No other factors were significantly predictive for compliance. The nurse survey demonstrated significant variability amongst the involved institutions, with regards to antiemetic prescribing practices. Conclusions: Computerized physician order entry is associated with impressive adherence to clinician prescribing practices, according to institutional guideline-directed antiemetic prophylaxis, for preventing acute and delayed CINV.

3501 Background: Cumulative neurotoxicity commonly leads to early discontinuation of oxaliplatin-based therapy. In a relatively small, prematurely-discontinued, randomized study, IV CaMg was associated with reduced oxaliplatin-induced sNT (Grothey, JCO, 2011). N08CB was designed to definitively test whether IV CaMg significantly decreases cumulative oxaliplatin-related sNT. Methods: 353 pts with colon cancer undergoing adjuvant therapy with FOLFOX were randomized to 3 arms: IV CaMg (1g calcium gluconate, 1g magnesium sulfate) before and after oxaliplatin vs PL before and after vs CaMg before and PL after. The primary endpoint was cumulative sNT repeatedly measured by the sensory subscale of the EORTC QLQ-CIPN20. Secondary endpoints, using CTCAE 4.0 and an oxaliplatin specific neurotoxicity scale, were also assessed. Acute neuropathy data were also collected for 5 days following each oxaliplatin dose. The area under the curve (AUC) of the sensory subscale during the treatment cycles was used as summary measures for comparison. The Wilcoxon rank-sum tests were conducted for each treatment versus placebo arm, at 2.5%, adjusting for multiplicity using Bonferroni’s approach. Results: CaMg did not reduce cumulative sNT. Primary and secondary analyses data are summarized in the Table. In addition, there were no significant differences between arms regarding oxaliplatin administered doses or chemotherapy discontinuation rates. Also, there were no substantial differences in acute neuropathy scores or side-effects between study arms. Conclusions: This study does not demonstrate any activity of IV CaMg as a neuroprotectant against oxaliplatin-induced neurotoxicity. Clinical trial information: NCT01099449. [Table: see text]

9075 Background: Chemotherapy-induced peripheral neuropathy (CIPN), a common dose-limiting side effect of chemotherapy, remains without known effective interventions. Preliminary data support that Scrambler therapy, a device which treats pain via non-invasive cutaneous electrostimulation, is beneficial for the treatment of CIPN. This pilot trial was performed to investigate the effect of Scrambler therapy for the treatment of CIPN. Methods: Eligible patients included those age ≥18 years, ECOG PS ≤2, life expectancy ≥3 months, with pain or CIPN symptoms of ≥1 month duration and tingling or pain ≥4/10 during the prior week. Patients were treated with Scrambler therapy to the affected area for up to 10 daily 30 minute sessions. Symptoms were monitored daily during therapy using a questionnaire to measure symptoms of neuropathy with a numerical analogue scale. Results: We report on the first 11 CIPN patients, enrolled between 7/18/2011 and 12/12/2011, 3 men and 8 women; mean age 57 years. Patients had history of exposure to various chemotherapeutic agents and the majority had symptoms >2 years. The table portrays data at baseline, at the end of the 10 planned days of therapy, and the percent changes from baseline to the end of treatment, regarding patient reported pain, tingling, and numbness over the preceding 24 hours. There were no adverse events. Persistent benefit out to 5 weeks was seen in some patients; maturing data will be available by May 2012. Descriptive summary statistics formed the basis of data analysis. Further patients are being entered on this trial. Conclusions: Scrambler therapy appears to be beneficial in the treatment of CIPN. A prospective placebo-controlled clinical trial should be performed to confirm these preliminary findings. [Table: see text]

Abstract Background: Contemporary approaches to non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) incorporate chemo-immunotherapy, biologic combinations, and immune modulating agents; toxicities in elderly pts (³65 years) receiving these therapies are not well studied. Further, clinical and biologic factors predicting these toxicities in pts receiving biologic therapy remain undefined. Methods: We reviewed data on NHL and/or CLL pts treated prospectively on 14 studies by the Alliance for Clinical Trials in Oncology from 2004-2014 (Table 1). Toxicity was assessed per the NCI CTCAE at the time of trial enrollment, and the probabilities of experiencing grade 3 and grade 4 hematologic (hem) and non-hematologic (non-hem) toxicities were modeled as a function of age (³65 years vs. < 65), time on study, treatment (biologics only vs. biologic + chemotherapy), gender, race, LDH, performance status (PS), stage, and an age-by-treatment interaction using logistic regression. Results: A total of 1199 pts (409 age ³ 65; 790 age < 65; 736=CLL and 463=NHL) were included. Among these patients, 493 received only biologic therapy (166 age ³ 65; 327 age < 65; 104 CLL; 389 NHL), and 706 received biologic + chemotherapy (243 age ³ 65; 463 age < 65; 632 CLL; 74 NHL). Among CLL pts (259 pts ³ 65), the effect of age on the probability of experiencing a grade 3 heme toxicity differed by treatment type (age-by-treatment interaction p = 0.047). Specifically, the adjusted odds ratio (OR) (age ³ 65 vs. < 65) for pts receiving only biologic therapy was 3.075 (95% CI: 1,15-8.25), and that for pts receiving biologic + chemotherapy was 1.044 (95% CI: 0.69 - 1.57). Similar results were seen in CLL pts for grade 4 heme toxicities (age-by-treatment interaction p = 0.033; biologic OR 6.937, 95% CI: 1.76-27.35; biologic + chemo OR 1.484, 95% CI: 1.04-2.13). No such interactions were found in CLL pts for grade 3 and 4 non-hem toxicities; however, older pts had significantly higher odds of experiencing a grade 3 non-hem toxicity than younger pts (adjusted OR 1.40; p = 0.047; 95% CI: 1.004-1.96). No age group differences were found in CLL pts for grade 4 non-hem toxicity. Similar analyses were performed for NHL pts (150 pts ³ 65), but no significant age group differences were found. Among CLL pts, women had significantly higher odds of experiencing a grade 3 heme toxicity than men (OR 2.01; p = 0.0007); no difference in grade 3 non-hem or any grade 4 toxicity was noted. Non-Caucasian CLL pts had higher odds of experiencing a grade 4 non-hem toxicity than Caucasians (OR 2.892; p = 0.0029), but no other toxicity differences were found. Worse PS was associated with increased toxicities (OR 1.871; p = 0.0009: grade 3 heme; OR 1.647; p = 0.0025: grade 3 non-hem; OR 1.410; p = 0.0448: grade 4 heme, and OR 1.931; p = 0.0252: grade 4 non-hem). CLL pts with advanced stage disease had higher odds of experiencing a heme toxicity (grade 3: OR 1.95; p = 0.0007, grade 4: OR 1.451; p = 0.0329), but no stage associations were found for non-hem toxicities. Among NHL pts, men had significantly higher odds of experiencing a grade 4 hematologic toxicity than women (OR 4.351; p = 0.0169), but no other toxicity differences were found. An increase in LDH was associated with significantly higher odds of experiencing grade 3 non-hem and grade 4 heme toxicities (grade 3 non-heme: OR 1.633; p = 0.021, grade 4 heme: OR 2.039, p = 0.0182), but no such effect was found for grade 3 heme or grade 4 non-hem. Worse PS was associated with higher odds of experiencing grade 3 toxicities (heme: OR 2.025; p = 0.0344, non-hem: OR 2.458; p = 0.0013), but no such differences were found for grade 4 toxicities. No significant stage or race effects were found in NHL patients. Conclusion: In pts ³65 years who have CLL or NHL, we identified several clinical and disease-related factors as potential predictors of developing grade 3 and/or 4 heme and non-hem toxicities (Table 2). A prognostic model is being constructed to predict toxicities in these under-studied pts to guide management and monitoring. Further, the impact of these toxicities on outcomes is being analyzed and will be presented at the meeting. Disclosures Hurria: Celgene: Other: Research; Optum Health Care SOlutions: Consultancy, Other: Conference panel, research; Boehringer Ingelheim Pharmaceuticals: Consultancy; Sanofi: Consultancy; Carevive: Consultancy; Novartis: Other: Research; GTx, Inc: Consultancy. Bartlett:Gilead: Consultancy. Cheson:Gilead: Research Funding; Acerta: Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Research Funding. Nabhan:Infinity: Consultancy; Abbvie: Consultancy; Cardinal Health: Consultancy; Seattle Genetics: Research Funding; Genentech: Consultancy, Research Funding; Astellas: Research Funding; Celgene Corporation: Consultancy, Research Funding.