Phase I Study of Muscadine Grape Extract for Patients With Advanced Cancer.

OBJECTIVE: Preclinical studies with muscadine grape extract (MGE) show antitumor activity and decreased systemic inflammation. This phase I study (NCT02583269) assessed safety and tolerability of a proprietary MGE preparation in patients with advanced solid tumors. METHODS: Patients with metastatic or unresectable cancers who were progressing on standard therapies were assigned to MGE in a standard 3+3 design. Five dose levels were tested (320 to 1600 mg total phenolics/d). Safety and maximum-tolerated dose were assessed after 4 weeks. Patients were evaluated for response at 8 weeks and continued on MGE if clinically stable. Secondary outcomes were response, survival, adherence, fatigue, and quality of life (QOL). RESULTS: In total, 23 patients (lung, n=7; gastrointestinal, n=7; genitourinary, n=6; other, n=3) received MGE capsules by mouth twice daily. The cohort [median age 72 years, 48% Eastern Cooperative Oncology Group (ECOG) 2] was heavily pretreated. After 4 weeks on MGE, possibly attributable adverse events grade 2 or higher were fatigue (n=1), decreased lymphocyte count (n=1), and constipation (n=2), including 1 dose-limiting toxicity for grade 3 constipation. Maximum-tolerated dose was not reached. No partial responses were observed. Median time on therapy was 8 weeks, with 29% of patients treated beyond 16 weeks and a median overall survival of 7.2 months. QOL and fatigue levels were stable from baseline to 8 weeks. Higher MGE dose was correlated with improvement in self-reported physical well-being QOL at 8 weeks (r=0.6; P=0.04). CONCLUSIONS: MGE is safe and well-tolerated in heavily pretreated and older cancer patients.  The potential anticancer properties and the effects of MGE on physical well-being and QOL metrics will be evaluated in future studies.

Trajectories of response to acupuncture for menopausal vasomotor symptoms: the Acupuncture in Menopause study.

OBJECTIVE: To examine the trajectories of responses to acupuncture treatment for menopausal vasomotor symptoms (VMS) and the characteristics of women in each trajectory. METHODS: Two hundred nine perimenopausal and postmenopausal women aged 45 to 60 years experiencing at least four VMS per day were recruited and randomized to receive up to 20 acupuncture treatments within 6 months or to a waitlist control group. The primary outcome was percent change from baseline in the mean daily VMS frequency. Finite mixture modeling was used to identify patterns of percent change in weekly VMS frequencies over the first 8 weeks. The Freeman-Holton test and analysis of variance were used to compare characteristics of women in different trajectories. RESULTS: Analyses revealed four distinct trajectories of change in VMS frequency by week 8 in the acupuncture group. A small group of women (11.6%, n = 19) had an 85% reduction in VMS. The largest group (47%, n = 79) reported a 47% reduction in VMS frequency, 37.3% (n = 65) of the sample showed only a 9.6% reduction in VMS frequency, and a very small group (4.1%, n = 7) had a 100% increase in VMS. Among women in the waitlist control group, 79.5% reported a 10% decrease in VMS frequency at week 8. Baseline number of VMS, number of acupuncture treatments in the first 8 weeks, and traditional Chinese medicine diagnosis were significantly related to trajectory group membership in the acupuncture group. CONCLUSIONS: Approximately half of the treated sample reported a decline in VMS frequency, but identifying clear predictors of clinical response to acupuncture treatment of menopausal VMS remains challenging.

Acupuncture in Menopause (AIM) study: a pragmatic, randomized controlled trial.

OBJECTIVE: The aim of the study was to evaluate the short and long-term effects of acupuncture on vasomotor symptoms (VMS) and quality of life-related measures. METHODS: A total of 209 perimenopausal and postmenopausal women aged 45 to 60 years, experiencing four or more VMS per day, were recruited from the community and randomized to receive up to 20 acupuncture treatments within the first 6 months (acupuncture group) or the second 6 months (waitlist control group) of the 12-month study period. The primary outcome was mean daily frequency of VMS. Secondary outcomes were VMS interference with daily life, sleep quality, depressive symptoms, somatic and other symptoms, anxiety, and quality of life. RESULTS: The VMS frequency declined by 36.7% at 6 months in the acupuncture group and increased by 6.0% in the control group (P < 0.001 for between-group comparison). At 12 months, the reduction from baseline in the acupuncture group was 29.4% (P < 0.001 for within-group comparison from baseline to 12 months), suggesting that the reduction was largely maintained after treatment. Statistically significant clinical improvement was observed after three acupuncture treatments, and maximal clinical effects occurred after a median of eight treatments. Persistent improvements were seen in many quality of life-related outcomes in the acupuncture group relative to the control group. CONCLUSIONS: We found that a course of acupuncture treatments was associated with significant reduction in VMS, and several quality-of-life measures, compared with no acupuncture, and that clinical benefit persisted for at least 6 months beyond the end of treatment.

Comorbidity, age, and mortality among adults treated intensively for acute myeloid leukemia (AML).

INTRODUCTION: Our goal was to characterize comorbidities among adults receiving intensive therapy for AML, and investigate their association with outcomes. METHODS: We retrospectively analyzed 277 consecutive patients with newly diagnosed AML treated intensively at the Comprehensive Cancer Center of Wake Forest University from 2002 to 2009. Pretreatment comorbidities were identified by ICD-9 codes and chart review. Comorbidity burden (modified Charlson Comorbidity Index [CCI]) and specific conditions were analyzed individually. Outcomes were overall survival (OS), remission, and 30-day mortality. Covariates included age, gender, cytogenetic characteristics, hemoglobin, white cell count, lactate dehydrogenase, body mass index, and insurance type. Cox proportional hazards models were used to evaluate OS; logistic regression was used for remission and 30-day mortality. RESULTS: In this series, 144 patients were ≥ 60 years old (median age 70 years, median survival 8.7 months) and 133 were <60 years (median age 47 years, median survival 23.1 months). Older patients had a higher comorbidity burden (CCI≥1 58% versus 26%, P<0.001). Prevalent comorbid conditions differed by age (diabetes 19.2% versus 7.5%; cardiovascular disease 12.5% versus 4.5%, for older versus younger patients, respectively). The CCI was not independently associated with OS or 30-day mortality in either age group. Among older patients, diabetes was associated with higher 30-day mortality (33.3% vs. 12.0% in diabetic vs. non-diabetic patients, p=0.006). Controlling for age, cytogenetic characteristics and other comorbidities, the presence of diabetes increased the odds of 30-day mortality by 4.9 (CI 1.6-15.2) times. DISCUSSION: Diabetes is adversely associated with 30-day survival in older AML patients receiving intensive therapy.

Outcomes of patients with esophageal cancer staged with [¹8F]fluorodeoxyglucose positron emission tomography (FDG-PET): can postchemoradiotherapy FDG-PET predict the utility of resection?

PURPOSE: To determine whether [(18)F]fluorodeoxyglucose positron emission tomography (FDG-PET) can delineate patients with esophageal cancer who may not benefit from esophagectomy after chemoradiotherapy. PATIENTS AND METHODS: We reviewed records of 163 patients with histologically confirmed stage I to IVA esophageal cancer receiving chemoradiotherapy with or without resection with curative intent. All patients received surgical evaluation. Initial and postchemoradiotherapy FDG-PET scans and prognostic/treatment variables were analyzed. FDG-PET complete response (PET-CR) after chemoradiotherapy was defined as standardized uptake value ≤ 3. RESULTS: Eighty-eight patients received trimodality therapy and 75 received chemoradiotherapy. Surgery was deferred primarily due to medical inoperability or unresectable/metastatic disease after chemoradiotherapy. A total of 105 patients were evaluable for postchemoradiotherapy FDG-PET response. Thirty-one percent achieved a PET-CR. PET-CR predicted for improved outcomes for chemoradiotherapy (2-year overall survival, 71% v 11%, P < .01; 2-year freedom from local failure [LFF], 75% v 28%, P < .01), but not trimodality therapy. On multivariate analysis of patients treated with chemoradiotherapy, PET-CR is the strongest independent prognostic variable (survival hazard ratio [HR], 9.82, P < .01; LFF HR, 14.13, P < .01). PET-CR predicted for improved outcomes regardless of histology, although patients with adenocarcinoma achieved a PET-CR less often. CONCLUSION: Patients treated with trimodality therapy found no benefit with PET-CR, likely because FDG-PET residual disease was resected. Definitive chemoradiotherapy patients achieving PET-CR had excellent outcomes equivalent to trimodality therapy despite poorer baseline characteristics. Patients who achieve a PET-CR may not benefit from added resection given their excellent outcomes without resection. These results should be validated in a prospective trial of FDG-PET-directed therapy for esophageal cancer.

Acupressure for chemotherapy-associated nausea and vomiting in children.

The objective of this study was to determine the feasibility and effectiveness of acupressure therapy in preventing chemotherapy-associated nausea in children. A prospective, randomized, crossover trial was conducted among pediatric oncology patients at Brenner Children's Hospital (Winston-Salem, NC). Patients were randomized to one of two treatment sequences involving acupressure wrist bands and placebo bands, separated by a standard care treatment with no bands. All patients received standard antiemetic therapy for each treatment. Expectations and outcomes of nausea and vomiting were assessed by questionnaires. Of 21 patients approached, 21 were enrolled and 18 completed all three study treatments. Patients' ages ranged from 5 to 19 years, 14 of 18 were Caucasian, and 9 were male. In general, patients expressed moderate expectations that acupressure would prevent nausea and vomiting. Following the session with an acupressure band, a third of all patients reported better than expected nausea prevention. There was no significant difference in nausea or vomiting between the three groups; there were no significant side effects from acupressure or placebo bands. Pediatric oncology patients have moderate expectations about the effectiveness of acupressure in preventing nausea and vomiting. Acupressure is feasible and well tolerated but was not more effective than placebo in this sample of patients who were also treated with standard antiemetic therapies.