A phase II study of combination daunorubicin, cytarabine (Ara-c), and nilotinib (TAsigna) (DATA) in patients newly diagnosed with acute myeloid leukemia with KIT expression.

Acute myeloid leukemia (AML) is a challenging cancer in terms of achieving and maintaining long-duration remissions. Many novel therapies have been added to the standard regimen (combining cytarabine and anthracycline "7 + 3") to achieve such goals. Nilotinib is an oral multikinase inhibitor that is active against KIT tyrosine kinase, an important stem cell target. In this trial, we combined nilotinib with 7 + 3 induction (daunorubicin 60 mg/m2), high-dose cytarabine consolidation, and subsequently, if the patient was a candidate, for 2 years' maintenance therapy in patients with AML and KIT (CD117) expression. Patients were allowed to proceed to allogeneic hematopoietic cell transplantation (HCT) if deemed necessary. Our primary goal was increased complete remission rate with this combination. Thirty-four patients (with a median age 58.5 years) were enrolled on a single-arm phase II bi-institutional study; 21 (62%) patients achieved remission. The complete remission rate was 78% in evaluable patients. Thirteen of 34 (38%) patients had allogeneic HCT, all thirteen of which are still alive (100%). Common (>20%) grade 3 non-hematological toxicities included febrile neutropenia, hypophosphatemia, elevated liver enzymes, and hypertension. Only one patient (3%) died in induction due to liver failure, which was thought secondary to daunorubicin. Our current study reveals good outcomes in patients who received HCT and may warrant a larger study to confirm our findings in that specific population.

A feasibility study of virtual group therapy to improve quality of life of cancer caregivers.

BACKGROUND: Cancer caregiving can negatively impact the quality of life (QOL) of the caregiver. In-person interventions for improving coping skills have been shown to be effective in improving QOL for caregivers. OBJECTIVES: This pilot project explored the feasibility and acceptability of a virtual group therapy intervention to improve short-term cancer caregiver QOL. METHODS: Caregivers of cancer patients were enrolled in a structured multidisciplinary intervention of eight virtual group therapy sessions provided over four weeks between September 9, 2013 and November 17, 2014. Group sessions were led by trained facilitators and included components of physical therapy, occupational therapy, psychosocial education, cognitive-behavioral intervention, supportive discussion, spiritual reflection, and mindfulness therapy. Feasibility was based on acceptable number of recruited participants per session; acceptability was defined using attendance and 80% QOL completion rates. QOL domains and symptom burden were assessed using validated single items. RESULTS: The 20 cancer caregivers who enrolled were mostly older (80% were ≥ 65 years), female (76.5%), married to the patient (88.2%), Caucasian (100%), and highly educated (100%). 60% attended one to five sessions, 15% attended six to eight sessions, and 25% attended no sessions. Thirty percent completed pre- and post- intervention ratings of QOL items. SIGNIFICANCE OF RESULTS: Findings suggested that a virtual group therapy intervention is feasible for the cancer caregivers in this study. Although not statistically significant, the caregivers reported higher QOL and less symptom burden in multiple domains after participating in the virtual group therapy intervention.

Phase 1 study of pomalidomide and dexamethasone for relapsed/refractory primary CNS or vitreoretinal lymphoma.

The combination of pomalidomide (POM) and dexamethasone (DEX) was evaluated for relapsed/refractory primary central nervous system lymphoma (PCNSL) and primary vitreoretinal lymphoma (PVRL) to determine the maximal tolerated dose (MTD) of POM as the primary objective, and overall response rate (ORR), progression-free survival (PFS), and safety profile as secondary objectives. A cohorts-of-3 study design was used with a dose-escalation schedule consisting of POM (3, 5, 7, or 10 mg) orally daily for 21 days every 28 days and DEX 40 mg orally every week. After 2 cycles, POM was continued alone until disease progression, intolerance, or subject withdrawal. Following MTD determination, the MTD cohort was expanded. Twenty-five of 29 patients with the median of 3 prior treatments were eligible for assessment as per international PCNSL collaborative group criteria. The MTD of POM was 5 mg daily for 21 days every 28 days. Whole-study ORR was 48% (12 of 25; 95% confidence interval [CI], 27.8%, 68.7%) with 6 complete response (CR), 2 complete response, unconfirmed (CRu), and 4 partial response (PR). MTD cohort ORR was 50% (8 of 16; 95% CI, 24.7%, 75.4%) with 5 CR, 1 CRu, and 2 PR. Median PFS was 5.3 months (whole study) and 9 months (for responders). One patient had pseudoprogression. Grade 3/4 hematologic toxicities included neutropenia (21%), anemia (8%), and thrombocytopenia (8%). Grade 3/4 nonhematologic toxicities included lung infection (12%), sepsis (4%), fatigue (8%), syncope (4%), dyspnea (4%), hypoxia (4%), respiratory failure (8%), and rash (4%). POM/DEX treatment is feasible with significant therapeutic activity against relapsed/refractory PCNSL and PVRL. This trial was registered at www.clinicaltrials.gov as #NCT01722305.

A randomized phase II trial evaluating two non-pharmacologic interventions in cancer survivors for the treatment of sleep-wake disturbances: NCCTG N07C4 (Alliance).

PURPOSE: Sleep disturbance is a prevalent problem for cancer survivors and effective behavioral treatments are not widely used for this population. This study evaluated home-based sleep interventions based on cognitive behavioral therapy for insomnia (CBT-I). METHODS: This phase II randomized controlled trial evaluated two manualized interventions over 7 weeks. The intervention group received sleep hygiene information, stimulus control, sleep restriction, and a bedtime imagery audio recording. The control group was similar, but without sleep restriction and used audio recordings of bedtime short stories instead of imagery. Eligibility included adult cancer survivors who had trouble falling asleep or falling back to sleep on 3 of 7 days. Patients with diagnoses of sleep or mental health disorders were excluded. The primary endpoint was change in time to fall asleep or falling back to sleep after awakening, from baseline to week 7. Two-sample T tests evaluated differences between arms for this endpoint. RESULTS: Ninety-three of 168 planned participants were enrolled from 20 institutions. The study closed early for poor accrual. Baseline time to sleep was 45 min and 52 min for the intervention and control group, respectively. At 7 weeks, both groups improved, the intervention group to 26 min and control group to 30 min, a non-significant difference between groups (p = 0.85). Secondary outcomes improved in both groups with no significant differences between arms. CONCLUSIONS: Improvement in sleep outcomes in both arms was consistent with other CBT-I interventions delivered through alternative approaches to provider-delivered therapy. More research on optimal scalable delivery of CBT-I is needed. CLINICAL RELEVANCE: This study supports the effectiveness of CBT-I based behavioral interventions for sleep but also the need for better delivery methods to improve uptake and effect size. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00993928.

Effects of a multidisciplinary quality of life intervention on sleep quality in patients with advanced cancer receiving radiation therapy.

OBJECTIVES: Sleep disturbances are prevalent in cancer patients, especially those with advanced disease. There are few published intervention studies that address sleep issues in advanced cancer patients during the course of treatment. This study assesses the impact of a multidisciplinary quality of life (QOL) intervention on subjective sleep difficulties in patients with advanced cancer. METHOD: This randomized trial investigated the comparative effects of a multidisciplinary QOL intervention (n = 54) vs. standard care (n = 63) on sleep quality in patients with advanced cancer receiving radiation therapy as a secondary endpoint. The intervention group attended six intervention sessions, while the standard care group received informational material only. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS), administered at baseline and weeks 4 (post-intervention), 27, and 52. RESULTS: The intervention group had a statistically significant improvement in the PSQI total score and two components of sleep quality and daytime dysfunction than the control group at week 4. At week 27, although both groups showed improvements in sleep measures from baseline, there were no statistically significant differences between groups in any of the PSQI total and component scores, or ESS. At week 52, the intervention group used less sleep medication than control patients compared to baseline (p = 0.04) and had a lower ESS score (7.6 vs. 9.3, p = 0.03). SIGNIFICANCE OF RESULTS: A multidisciplinary intervention to improve QOL can also improve sleep quality of advanced cancer patients undergoing radiation therapy. Those patients who completed the intervention also reported the use of less sleep medication.

Evaluating the efficacy of vaginal dehydroepiandosterone for vaginal symptoms in postmenopausal cancer survivors: NCCTG N10C1 (Alliance).

BACKGROUND: Women with estrogen deficiencies can suffer from vaginal symptoms that negatively impact sexual health. This study evaluated vaginal dehydroepiandrosterone (DHEA) for alleviation of vaginal symptoms. METHODS: This three-arm randomized, controlled trial evaluated DHEA 3.25 mg and DHEA 6.5 mg, each compared to a plain moisturizer (PM) over 12 weeks, to improve the severity of vaginal dryness or dyspareunia, measured with an ordinal scale, and overall sexual health using the Female Sexual Function Index (FSFI). Postmenopausal women with a history of breast or gynecologic cancer who had completed primary treatment, had no evidence of disease, and reported at least moderate vaginal symptoms were eligible. The mean change from baseline to week 12 in the severity of vaginal dryness or dyspareunia for each DHEA dose was compared to PM and analyzed by two independent t tests using a Bonferroni correction. RESULTS: Four hundred sixty-four women were randomized. All arms reported improvement in either dryness or dyspareunia. Neither DHEA dose was statistically significantly different from PM at 12 weeks (6.25 mg, p = .08; 3.25 mg, p = 0.48), although a significant difference at 8 weeks for 6.5 mg DHEA was observed (p = 0.005). Women on the 6.5 mg arm of DHEA reported significantly better sexual health on the FSFI (p < 0.001). There were no significant differences in provider-graded toxicities and few significant differences in self-reported side effects. CONCLUSION: PM and DHEA improved vaginal symptoms at 12 weeks. However, vaginal DHEA, 6.5 mg, significantly improved sexual health. Vaginal DHEA warrants further investigation in women with a history of cancer.

Systemic and local effects of vaginal dehydroepiandrosterone (DHEA): NCCTG N10C1 (Alliance).

BACKGROUND: Dehydroepiandrosterone (DHEA) is helpful for treating vaginal symptoms. This secondary analysis evaluated the impact of vaginal DHEA on hormone concentrations, bone turnover, and vaginal cytology in women with a cancer history. METHODS: Postmenopausal women, diagnosed with breast or gynecologic cancer, were eligible if they reported at least moderate vaginal symptoms. Participants could be on tamoxifen or aromatase inhibitors (AIs). Women were randomized to 3.25 versus 6.5 mg/day of DHEA versus a plain moisturizer (PM) control. Sex steroid hormone levels, biomarkers of bone formation, vaginal pH, and maturation index were collected at baseline and 12 weeks. Analysis included independent t tests and Wilcoxon rank tests, comparing each DHEA arm with the control. RESULTS: Three hundred forty-five women contributed evaluable blood and 46 contributed evaluable cytology and pH values. Circulating DHEA-S and testosterone levels were significantly increased in those on vaginal DHEA in a dose-dependent manner compared to PM. Estradiol was significantly increased in those on 6.5 mg/day DHEA but not in those on 3.25 mg/day DHEA (p < 0.05 and p = 0.05, respectively), and not in those on AIs. Biomarkers of bone formation were unchanged in all arms. Maturation of vaginal cells was 100% (3.25 mg/day), 86% (6.5 mg/day), and 64% (PM); pH decreased more in DHEA arms. CONCLUSION: DHEA resulted in increased hormone concentrations, though still in the lowest half or quartile of the postmenopausal range, and provided more favorable effects on vaginal cytology, compared to PM. Estrogen concentrations in women on AIs were not changed. Further research on the benefit of vaginal DHEA is warranted in hormone-dependent cancers.

Electronic patient-reported outcomes and toxicities during radiotherapy for head-and-neck cancer.

PURPOSE: To characterize quality of life (QOL) using real-time, electronic patient-reported outcomes (ePROs) and to evaluate adverse events (AEs) and supportive care during head-and-neck radiotherapy (RT) and concurrent chemoradiotherapy (CCRT). METHODS: Sixty-five patients undergoing head-and-neck RT completed electronic, real-time, 12-item linear analog self-assessments (LASA) at baseline, before biweekly appointments, and at the last week of RT. Changes in QOL domains between time points were calculated. Clinical data were collected from the institutional medical record. AEs were recorded at the same time points as the LASA and graded. RESULTS: During head-and-neck RT, most patients had clinically meaningful decreases in all QOL domains except level of support, financial concerns, and legal concerns. QOL domains with the most prevalent, clinically meaningful decreases were fatigue (75.4% of patients; 95% CI, 62.9-84.9%), social activity (70.8%; 95% CI, 58.0-81.1%), and overall QOL (70.8%; 95% CI, 58.0-81.1%). All patients had grade 2 AEs; 35.4% had grade 3 (50.0%, CCRT; 12.0%, RT; P = .002). Weight loss averaged 5.5 kg (6.9 kg, CCRT; 2.8 kg, RT; P < .001). Intravenous hydration was needed in 52.3% (77.5%, CCRT; 12.0%, RT; P < .001); feeding tube placement 40.0% (57.5%, CCRT; 12.0%, RT; P = .001); emergency department visits without hospitalization, 10.8%; and emergent hospitalization, 27.7% (37.5%, CCRT; 12.0%, RT; P = .04). CONCLUSIONS: Head-and-neck RT, particularly CCRT, negatively impacts patients' overall QOL, social activity, and fatigue, with frequent grade 3 AEs, weight loss, intravenous hydration, feeding tube placement, ED visits, and hospitalization. Real-time ePROs allow providers to monitor QOL at multiple time points during RT, potentially allowing early intervention to improve QOL and mitigate AEs.

Longitudinal adverse event assessment in oncology clinical trials: the Toxicity over Time (ToxT) analysis of Alliance trials NCCTG N9741 and 979254.

BACKGROUND: Traditional methods of reporting adverse events in clinical trials are inadequate for modern cancer treatments with chronic administration. Conventional analysis and display of maximum grade adverse events do not capture toxicity profiles that evolve over time or longer lasting, lower grade toxic effects; we aimed to address this shortcoming in this study. METHODS: We developed an analytic approach and standardised, comprehensive format, the Toxicity over Time (ToxT) approach, which combines graphs and adverse event tabular displays with multiple longitudinal statistical techniques into a readily applicable method to study toxic effects. Plots visualising summary statistics or individual patient data over discrete timepoints were combined with statistical methods including the following longitudinal techniques: repeated measures models that describe the changes in adverse events across all cycles of treatment; time-to-event analyses of first and worst grade toxicity; and area under the curve (AUC) analyses summarising adverse event profiles over the entire course of a study, including chronic low-grade events. We applied ToxT analysis to adverse event data from two completed North Central Cancer Treatment Group (NCCTG/Alliance) trials: N9741 (NCT00003594), in which different combinations of oxaliplatin, 5-fluorouracil, and irinotecan were investigated for metastatic colorectal cancer, and 979254, in which survivors of breast cancer were given venlafaxine or placebo for control of hot flashes. FINDINGS: In trial NCCTG 979254 there was a higher incidence of late-occurring dry mouth in patients who were given venlafaxine than in those given placebo (week 1 [baseline]: 13% [six incidence in 48 patients, SD 5] vs 22% [11/49, SD 6]; p=0·20; week 5: 49% [24/49, 7] vs 2% [1/46, 2]; p<0·0001). In trial NCCTG N9741 there was an increased incidence of early nausea for patients given irinotecan plus oxaliplatin (IROX) compared with those given 5-fluorouracil plus oxaliplatin (FOLFOX; cycle 1 mean grade nausea 1·1 [SD 1·0] vs 0·6 [0·7]; p<0·0001). Event charts showed earlier occurrences of higher grades of diarrhoea for patients given IROX compared with those given FOLFOX, and the AUC analysis shows a higher magnitude of diarrhoea consistently over time throughout the study in patients given IROX versus those given FOLFOX (mean AUC 4·2 [SD 5·2] vs 2·9 [4·2]; p<0·0001). INTERPRETATION: The ToxT analytical approach incorporates the dimension of time into adverse event assessment and offers a more comprehensive depiction of toxic effects than present methods. With new, continuously administered targeted agents, immunotherapy, and maintenance regimens, these improved longitudinal analyses are directly relevant to patients and are crucial in cancer clinical trials. FUNDING: National Cancer Institute of the National Institutes of Health and the Mayo Comprehensive Cancer Center.

Cancer caregiver quality of life: need for targeted intervention.

OBJECTIVES: Caregiving can negatively impact well-being. Cancer caregivers face unique challenges given the intense nature of cancer and treatment, which increases their risk for burden, poor quality of life (QOL), and burnout. Studies to reduce caregiver burden demonstrate QOL improvement and distress reduction in the short term. However, few studies exist to address long-term benefits. We assessed changes in various QOL domains after participation in a QOL intervention for caregivers of patients having newly diagnosed advanced cancer. METHODS: Our institutional review board-approved study randomized patient-caregiver dyads to either usual care or an in-person group intervention composed of six 90-min sessions of structured multidisciplinary QOL components delivered over 4 weeks, with 10 follow-up phone calls within 20 weeks. Caregivers attended four of the six sessions attended by patients. Sessions included physical therapy, coping and communication strategies, mental health education, spirituality, and social needs. Caregiver QOL (Caregiver Quality of Life Index-Cancer Scale [CQOLC] and Linear Analogue Self-Assessment [LASA]) and mood (Profile of Mood States-Brief [POMS-B]) were measured at baseline and 4, 27, and 52 weeks. Wilcoxon tests and effect sizes were used to compare the caregiver groups. RESULTS: Of the 131 caregivers (65 intervention and 66 usual care), 116 completed the study. Caregivers post-intervention (at 4 weeks) had improved scores on LASA Spiritual Well-being; POMS-B total score, Vigor/Activity, and Fatigue/Inertia; and CQOLC Adaptation. At long term (at 27 weeks), caregivers retained improvement in POMS-B Fatigue/Inertia and gained improvements in CQOLC Disruptiveness and Financial Concerns. CONCLUSIONS: Caregivers who received the intervention had higher QOL ratings for specific QOL domains but not for overall QOL. Although a comprehensive intervention was helpful, more specific, targeted interventions tailored for individual needs are recommended. Copyright © 2015 John Wiley & Sons, Ltd.

Phase II evaluation of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes.

PURPOSE: Hot flashes are a significant source of symptom burden that negatively impacts quality of life (QOL). For women who have contraindications to, or are unwilling to consider, estrogens or antidepressants for bothersome hot flashes, there are limited effective pharmacologic or complementary and alternative medicines. METHODS: This single-arm phase II trial studied the efficacy of S-adenosyl-L-methionine (SAMe) for the treatment of hot flashes. Eligible women were required to have reported ≥14 hot flashes per week for ≥1 month. The patients were treated with SAMe at a dose of 400 mg twice daily to evaluate whether a reduction in hot flash score appeared to be better than the historical placebo response of approximately 25%. The women kept a daily hot flash diary during a baseline week and then daily during weeks 2-7. The primary endpoint was the change from baseline to week 7 in hot flash score and hot flash frequency. Secondary endpoints included toxicity analyses and the effect of SAMe on QOL. RESULTS: From October 28, 2010 to January 30, 2012, 43 women were treated with SAMe. The decrease in mean percent of baseline hot flash score and frequency was 35.4 and 32.6%, respectively. When compared to the historical placebo response of 25%, the effect of SAMe on hot flash score was not statistically significant (p = 0.09). Treatment was well tolerated with expected grade 1/2 gastrointestinal toxicity and no negative effect on QOL. CONCLUSIONS: The use of SAMe does not appear to significantly reduce hot flashes more than would be expected with a placebo.

MC11C4: a pilot randomized, placebo-controlled, double-blind study of venlafaxine to prevent oxaliplatin-induced neuropathy.

PURPOSE: Previous pilot data suggested that venlafaxine could prevent acute and chronic oxaliplatin-related neuropathy. The purpose of this randomized, placebo-controlled, double-blinded pilot study was to obtain additional data to support conducting a phase III trial to test the use of venlafaxine to prevent oxaliplatin neurotoxicity. METHODS: Fifty patients, scheduled to undergo oxaliplatin-based therapy (FOLFOX) for stages II-III (67%) or stage IV (33%) colon cancer, were randomized to receive venlafaxine extended release (37.5 mg) or placebo, twice daily, through their last dose of oxaliplatin and then titrated off. Neurotoxicity was evaluated via several patient- and physician-reported measures, including the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Chemotherapy-Induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20) instrument. RESULTS: Baseline patient characteristics were equivalent for the two arms, with a median age of 60 years. There was a trend toward benefit for the venlafaxine arm, when evaluated by the oxaliplatin-specific neuropathy scale and by acute neuropathy measures of throat discomfort and discomfort swallowing cold liquids, the latter only for the first two oxaliplatin doses. These trends were outweighed by a lack of any such trends in all other measurements including the following: (1) the CIPN20 sensory subscale (P = 0.55, primary endpoint), physician-completed NCI CTCAE assessment, or cumulative administered oxaliplatin doses (median 716 vs 631 mg for placebo and venlafaxine, respectively, P = 0.34). CONCLUSIONS: The present study neither supports the use of venlafaxine for preventing oxaliplatin-induced neuropathy in clinical practice nor the initiation of a phase III trial to investigate venlafaxine in this setting.

Zoledronic acid for treatment of osteopenia and osteoporosis in women with primary breast cancer undergoing adjuvant aromatase inhibitor therapy: a 5-year follow-up.

PURPOSE: This study was designed to explore whether zoledronic acid could prevent expected loss of bone mineral density (BMD) in postmenopausal women with pre-existing osteopenia or osteoporosis who were initiating adjuvant letrozole therapy for primary breast cancer. METHODS: Between June 2006 and July 2007, 60 postmenopausal women with estrogen and/or progesterone receptor-positive breast cancer and a BMD T-score ≤-2.0 were enrolled. Participants received letrozole 2.5 mg and vitamin D 400 IU daily, calcium 500 mg twice daily, and zoledronic acid 4 mg every 6 months for a maximum of 5 years or until disease progression. BMD at the lumbar spine and femoral neck was recorded at the start of the study and annually for 5 years. Patients were evaluated for fractures every 6 months for the duration of the trial. RESULTS: After 5 years, mean BMD increased significantly by 11.6% (p = 0.01) at the lumbar spine and by 8.8% (p = 0.01) at combined sites. Femoral neck BMD increased by 4.2%, although this was not significant (p = 0.23). At the end of the trial, BMDs were consistent with osteoporosis in 7 % and osteopenia in 36% of the patients. A total of six fractures were reported after 417 individual assessments. CONCLUSIONS: Zoledronic acid appears to prevent further bone loss in postmenopausal breast cancer patients with osteopenia and osteoporosis starting treatment with letrozole. These findings were maintained at 5 years and support concurrent initiation of bisphosphonate and aromatase inhibitor therapy in this high-risk population.

Can pregabalin prevent paclitaxel-associated neuropathy?--An ACCRU pilot trial.

PURPOSE: Paclitaxel can cause an acute pain syndrome (P-APS), considered to be an acute form of neuropathy and chronic chemotherapy-induced peripheral neuropathy (CIPN). Anecdotal reports suggested that gabapentin may be helpful in the prevention of these toxicities. The purpose of this pilot study was to obtain data to support or refute the utility of pregabalin for the prevention of P-APS and CIPN. METHODS: Patients scheduled to receive weekly paclitaxel (80 mg/m(2)/dose) were randomized 1:1 to receive pregabalin 75 mg or a placebo, twice daily, during the 12 weeks of chemotherapy. Patients completed the European Organization of Research and Treatment of Cancer Quality of Life (EORTC QLQ) CIPN20 questionnaire at baseline, prior to each dose of paclitaxel and monthly for 6 months post-treatment. Patients completed a post-paclitaxel questionnaire for 6 days after each dose of paclitaxel and an acute pain syndrome symptom questionnaire on day 8. The primary end point was to determine the effect of pregabalin on the maximum of the worst acute pain scores for the week following paclitaxel administration for cycle 1. RESULTS: Forty-six patients were randomly assigned to the treatment or placebo arm. There was no suggestion of a difference between the two study arms with regard to P-APS measures. While there was a suggestion that pregabalin decreased numbness, there was no suggestion that it decreased tingling, pain, or the EORTC QLQ-CIPN20 subscale scores. There were no evident toxicity differences between the two study arms. CONCLUSIONS: The results of this pilot trial do not support that pregabalin is helpful for preventing P-APS or paclitaxel-associated CIPN.

Repeated measures analyses of dermatitis symptom evolution in breast cancer patients receiving radiotherapy in a phase 3 randomized trial of mometasone furoate vs placebo (N06C4 [alliance]).

PURPOSE: Radiotherapy-related dermatological toxicities over time have not been well quantified. We examined during and immediately following radiation therapy skin toxicities over time in a randomized study of mometasone furoate vs placebo during breast radiotherapy. MATERIAL AND METHODS: Patients with breast cancer undergoing radiotherapy to the breast or chest wall were randomized. Symptoms related to skin toxicity were addressed weekly using provider-reported Common Terminology Criteria for Adverse Events (CTCAE v3.0) and 4 patient-reported outcomes (PRO) surveys. We applied repeated measures and risk analysis methodologies. RESULTS: One hundred seventy-six patients were enrolled. By CTCAE, significant differences favoring mometasone were detected over time in all toxicities except skin striae, atrophy, and infection. Statistically significant differences between arms at baseline but not over time occurred for all Linear Analog Self-Assessment. Statistically significant differences occurred for all symptoms in the temporal profile of symptoms as measured by PRO surveys (all P < .001). CONCLUSIONS: The use of longitudinal methods enhanced the ability of PRO tools to detect differences between study arms. Our results strengthened the conclusions of the original report that mometasone reduced acute skin toxicities. PRO surveys can accurately assess patients' experiences of symptom type and intensity over time and should be included in future clinical trials. For radiotherapy-related dermatological toxicity, we hypothesized that clinically significant differences over time, if any, can be found by repeated measures. We examined the acute skin toxicities in a randomized study of mometasone vs placebo during breast radiotherapy. For secondary end points, we showed that longitudinal methods enhanced the detection of differences between study arms and strengthened the conclusions from the original report. Frequent patient-reported outcome surveys over time should be included in future clinical trials.

Patient-reported outcomes questionnaire compliance in Cancer Cooperative Group Trials (Alliance N0992).

BACKGROUND/AIMS: The use of patient-reported outcomes in clinical trials is a focal point for research and policy. Non-compliance with planned questionnaires and missing data can threaten both internal validity and generalizability. This retrospective analysis was conducted to determine the extent of, and characteristics associated with, missing patient-reported outcomes. METHODS: Study characteristics, patient characteristics and adverse events, and reasons for non-compliance were compiled from 14 closed Alliance for Clinical Trials in Oncology, Mayo Clinic Cancer Center, or Mayo Clinic Cancer Research Consortium clinical trials. Compliance rates were calculated for each patient using the number of booklets completed while the patient was on trial divided by the number of booklets the patient was expected to complete. Frequency counts and summary statistics were compiled. Logistic regression techniques were employed. RESULTS: The 1640 included patients had a median age of 58 years and were mostly White (90.8%) and female (73.8%). Compliance rates per study ranged from 84.7% to 97.2%. The primary endpoint of overall compliance rate was 93.1%. A total of 1267 patients were compliant. Those non-compliant were slightly older (mean = 58.6 vs 57.5, p = 0.03) and had different types of cancers (p < 0.01). There were no differences in compliance according to tumor status (p = 0.66), clinical stage (p = 0.81), baseline quality of life (p = 0.42 for ≥8 vs <8 and p = 0.12 for ≥6 vs <6), or maximum adverse event grade incidence (p = 0.33 for grade 2+ incidence and p = 0.36 for grade 3+ incidence). Reasons for non-compliance included patient refusal (N = 136), booklet not administered to patient (N = 199), no clinic visit at the scheduled time for booklet completion (N = 40), and at-home-completed booklet not returned (N = 224). Logistic regression indicates gender (p < 0.01), race (p < 0.01), performance score (p = 0.02), dose delay status (p = 0.01), and incidence of grade 3 or higher adverse event (p = 0.03) were correlates of compliance. CONCLUSION: Patient-reported outcomes have successfully been implemented into Alliance and Mayo Clinic trials with high rates of patient compliance. Further improvement in compliance can be made with staff commitment and education. Patients are typically non-compliant only when the task at hand is burdensome, unclear, or logistically challenging. Existing tracking systems used for the other trial outcomes should be utilized to ensure successful capture of patient-reported outcomes.

Cancer Caregiver: Perceived Benefits of Technology.

BACKGROUND: The burden associated with caregiving has been well documented. Caregivers have multiple responsibilities, and technology may be accessible as a potential burden-alleviating resource. MATERIALS AND METHODS: We surveyed cancer caregivers regarding current technology use and willingness to use technology for easing burden or distress. Because age has been associated with technology use, responses were compared between geriatric (≥65 years old) and nongeriatric (18-64 years old) caregivers. RESULTS: We had 112 respondents. Based on nonmissing responses, 66% (n=71) were women, 95% (n=106) were white, and 84% (n=91) had post-high school education. Almost all caregivers reported having Internet (105 [94%]) and e-mail (102 [91%]) access. Nongeriatric caregivers indicated more willingness to access Internet-based tools that help caregivers (54 [93%] versus 41 [76%]; p=0.04) and were more frequent users of social media (37 [64%] versus 16 [30%]; p=0.01), smartphones (33 [57%] versus 16 [30%]; p=0.01), and other mobile wireless devices (42 [72%] versus 19 [35%]; p<0.001) than geriatric caregivers. They also more frequently expected technologies to improve their own quality of life (p=0.009), increase their feelings of being effective as a caregiver (p=0.02), and save time (p=0.003). Regardless of age, a majority of caregivers (67 [62%]) endorsed the potential benefit of caregiving technologies in preventing burnout. CONCLUSIONS: Most caregivers have high access to and use of technology. Geriatric and nongeriatric caregivers were receptive to technology-based tools to help with their caregiving roles. Although nongeriatric caregivers expected to derive more benefit from such tools, both groups believed that caregiving technologies could reduce burden.

North Central Cancer Treatment Group/Alliance trial N08CA-the use of glutathione for prevention of paclitaxel/carboplatin-induced peripheral neuropathy: a phase 3 randomized, double-blind, placebo-controlled study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a significant side effect of taxane and platinum-based chemotherapy. Several studies have supported the potential benefit of glutathione for the prevention of platinum-induced CIPN. The current trial was designed to determine whether glutathione would prevent CIPN as a result of carboplatin/paclitaxel therapy. METHODS: In total, 185 patients who received treatment with paclitaxel and carboplatin were accrued between December 4, 2009 and December 19, 2011. Patients were randomized to receive either placebo (n = 91) or 1.5 g/m(2) glutathione (n = 94) over 15 minutes immediately before chemotherapy. CIPN was assessed using the European Organization for Research and Treatment of Cancer Quality-of-Life (EORTC-QLQ) 20-item, CIPN-specific (CIPN20) sensory subscale and the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. RESULTS: There were no statistically significant differences between the 2 study arms with regard to: 1) peripheral neurotoxicity, as assessed using both the EORTC-QLQ-CIPN20 (P = .21) and the CTCAE scales (P = .449 for grade ≥2 neurotoxicity; P = .039 for time to development of grade ≥2 neuropathy, in favor of the placebo); 2) the degree of paclitaxel acute pain syndrome (P = .30 for patients who received paclitaxel every 3-4 weeks and P = .002, in favor of the placebo, for patients who received weekly paclitaxel); 3) the time to disease progression (P = .63); or 4) apparent toxicities. Subgroup analyses did not reveal any evidence of benefit in any particular subgroup. CONCLUSIONS: The results from this study do not support the use of glutathione for the prevention of paclitaxel/carboplatin-induced CIPN.

Spiritual quality of life in advanced cancer patients receiving radiation therapy.

OBJECTIVE: The aim of this randomized controlled trial for patients with advanced cancer receiving radiation therapy was to determine the effect of a multidisciplinary intervention on spiritual quality of life (QOL) at the end of the intervention (week 4) and at two follow-up time points (weeks 26 and 52). METHODS: One hundred thirty-one persons were randomized to either the intervention or control (forms only) groups. The intervention included six 90-min in-person sessions based on the physical, emotion, social, and spiritual domains of QOL. Three sessions included the spiritual component. Caregivers were present for four sessions, one which included a spiritual component. Ten follow-up phone calls were made to the patients in the intervention group during the 6-month follow-up period. Patients completed the Functional Assessment of Cancer Therapy: General Scale, the Linear Analog Self-Assessment which includes an assessment of spiritual QOL, and the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being (FACIT-Sp) at enrollment, and weeks 4, 27, and 52. RESULTS: Following the intervention, the intervention group demonstrated improved spiritual QOL on the FACIT-Sp, whereas the spiritual QOL of the control group decreased, resulting in significant mean changes between groups (total score: 1.7 vs. -2.9; p < 0.01; meaning/peace subscale: 1.0 vs. -3.5; p < 0.01; faith subscale: 3.1 vs. -1.7; p = 0.04). CONCLUSIONS: The results indicate that a multidisciplinary intervention which includes a spiritual component can maintain the spiritual QOL of patients with advanced cancer during radiation therapy.