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

Abstract

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.

Dietary Supplements in People with Metastatic Cancer Who Are Experiencing Malnutrition, Cachexia, Sarcopenia, and Frailty: A Scoping Review

“…The 48 articles were classified into the following categories: full text peer-reviewed manuscripts (n = 38), conference abstracts (n = 8), and clinical trial registrations (n = 2). Of the full text peer-reviewed manuscripts, the majority reported on randomized controlled trials (RCTs) (n = 18) [34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51], followed by quasi-experimental trials (n = 15) [52][53][54][55][56][57][58][59][60][61][62][63][64][65][66], retrospective cohort observational studies (n = 2) [67,68], and case studies (n = 3) [69][70][71]. Conference abstracts reported on RCTs (n = 3) [72][73][74], quasi-experimental trials (n = 4) [75][76][77][78], and a case study (n = 1) [79].…”

“…Other dietary supplements that were investigated were β-hydroxybutyrate (BHB) [81], coenzyme Q10 [56], muscadine grape extract [52], dietary nucleotides [67], and royal jelly [34]. The supplement BHB was included in a quasi-experimental trial that has not started recruitment yet and will be administered in the form of liquid ketone supplement, two tablespoons three times daily (providing 1 g/kg body weight daily of BHB) [81].…”

“…Coenzyme Q10 was administered in a quasi-experimental trial in the form of one pack of enriched ONS (Inner Power ® which contains BCAA, carnitine, and 30 mg coenzyme Q10 per pack) daily [56]. Muscadine grape extract was investigated in a quasi-experimental trial in the form of capsules that were taken twice daily (each capsule containing ~160 mg phenolics) in five dose levels of 320 to 1600 mg total phenolics [52]. Royal jelly was administered in the form of 800 mg capsules three times daily (equivalent to 2400 mg daily), as per figures published in the erratum [82].…”

“…Of the 48 studies, single dietary supplements were administered on their own, without concomitant interventions, in 19 studies (e.g., omega-3 only) [34,38,40,41,47,52,55,59,[62][63][64][65][66]70,72,75,[77][78][79]. The remaining 29 studies had single dietary supplements administered with other dietary supplements (e.g., omega-3 and arginine), ONS, counseling, exercise, and/or non-cancer specific drugs.…”

“…The malnutrition-related conditions investigated in the included studies included cachexia (n = 14) [37,44,50,51,56,57,63,[70][71][72][73][74]77,78], weight loss (n = 10) [35,41,42,45,47,48,[54][55][56]65], malnutrition (n = 6) [36,38,39,48,58,67], vitamin D deficiency (n = 3) [40,59,64], anorexia (n = 2) [37,47] vitamin B6 deficiency (n = 1) [70], muscle depletion (n = 1) [56], and cancerrelated anemia (n = 1) [43]. The specific malnutrition-related conditions were not specified in other studies (n = 15) [34,46,49,52,53,[60][61][62]66,68,…”