Cachexia

The guideline provides evidence- and consensus-based recommendations on the management of cancer cachexia, without quantifying a singular intervention effect.

ESMO Clinical Practice Guideline for cachexia in adult cancer patients; multidisciplinary expert consensus recommendations on screening, assessment and multimodal cachexia treatment. Official professional society guideline.

There is no sufficient evidence for a clinically meaningful benefit of cannabis or cannabinoids on morbidity and mortality in HIV/AIDS.

Cochrane SR (k=7 RCTs) on cannabis/cannabinoids in HIV/AIDS-associated cachexia syndrome. Only evaluable weight study (n=139): dronabinol increased the probability of weight gain ≥2 kg by RR=2.09 (95% CI 0.72–6.06) versus placebo; mean weight gain +0.1 kg vs. −0.4 kg (placebo). CI includes 1 — evidence for efficacy in cachexia currently insufficient.

Cannabinoids showed no significant advantage over placebo in cancer patients for caloric intake, appetite, nausea/vomiting, pain or sleep problems; in HIV patients a benefit for weight gain and appetite was demonstrable, but overall no convincing high-quality evidence was found for the benefit of cannabinoids in anorexia or cachexia.

Systematic review and meta-analysis on cannabinoids in palliative medicine; k=9 RCTs (n=1.561). In cancer patients no significant differences vs. placebo for caloric intake (SMD: 0.2, 95% CI: [-0.66, 1.06], p=0.65) or appetite (SMD: 0.81, 95% CI: [-1.14, 2.75], p=0.42). In HIV patients cannabinoids superior for weight gain (SMD: 0.57 [0.22; 0.92], p=0.001) and appetite (SMD: 0.57 [0.11; 1.03], p=0.02). GRADE evidence quality: low to very low.

Cannabis-based medicines showed no significant advantage over placebo/active treatments for appetite, weight or quality of life in cachexia treatment.

Systematic review + meta-analysis on cannabis in anorexia-cachexia syndrome; k=5 RCTs (n=934). Pooled effect for change in appetite SMD=-1.79 (95% CI: -3.77 to 0.19) favoring control (p=0.08); no significant differences for weight gain or quality of life. Evidence quality (GRADE): low.

Cannabinoids increased appetite, but worsened quality of life and led to frequent side effects.

Systematic review and meta-analysis on medical cannabinoids in tumor cachexia; analysis of RCTs on appetite, weight and quality of life. Evidence for moderate improvement of appetite and nausea, but limited effect on weight gain.

Meta-analysis shows no significant benefits of cannabinoids for appetite, weight gain and quality of life in cancer-associated cachexia; moderate-quality evidence even suggests significantly worse quality of life.

Systematic review + meta-analysis on cannabinoids in cancer cachexia; k=10 studies (4 RCTs + 6 NRSIs). Meta-analysis (very low quality of evidence): no significant appetite benefit vs. control (SMD=-0.02; 95% CI: -0.51 to 0.46; p=0.93). Moderate evidence: cannabinoids significantly worse than control for quality of life (SMD=-0.25).

THC and nabilone were more effective than placebo against chemotherapy-induced nausea and vomiting, but not more effective than other antiemetics; insufficient evidence for other gastrointestinal symptoms.

MASCC Expert Opinion/Consensus Guidance on cannabinoids for gastrointestinal symptoms (incl. anorexia-cachexia syndrome) in cancer patients. Systematic review identified 36 RCTs (31 on CINV, 4 on anorexia-cachexia/taste disorders). Populations heterogeneous, many studies of low methodological quality. For anorexia-cachexia: four RCTs included, evidence limited by methodological weaknesses (unclear randomization, blinding, allocation concealment).

Cannabinoids do not improve appetite, oral food intake, weight, taste function or appetite-related quality of life in cancer patients.

Systematic review on cannabinoids in cancer-associated cachexia; k=6 RCTs over 20 years. Cannabinoids improved neither appetite, nor oral intake, weight, chemosensory function or appetite-related quality of life. Limitations: small sample sizes, lack of confounder adjustment.

Dronabinol was significantly inferior to megestrol acetate in the treatment of tumor-related anorexia; the combination provided no additional benefit.

n=469 advanced cancer patients with cachexia, 3-arm RCT: megestrol acetate 800 mg/d vs. dronabinol 2.5 mg 2×/d vs. combination. Megestrol acetate showed superior appetite improvement (75% vs. 49%, p=0.0001) and weight gain ≥10% (11% vs. 3%, p=0.02) compared to dronabinol. Combination without additional benefit vs. megestrol acetate alone.

Megestrol acetate 750 mg (±dronabinol) produced significant weight gain, while dronabinol alone showed weight loss.

n=52 HIV wasting patients, dronabinol 2.5 mg 2×/d vs. megestrol 750 mg/d vs. combinations, 12 weeks; mean weight change dronabinol monotherapy: -2.0 ± 1.3 kg vs. megestrol 750 mg: +6.5 ± 1.1 kg (p<0.0001); dronabinol alone inferior in weight gain.

Cannabis and dronabinol significantly increase caloric intake in HIV patients with loss of muscle mass.

n=30 HIV-positive cannabis users (n=15 with clinically significant loss of muscle mass <90% BCM/height, n=15 without), randomized comparison of dronabinol (10/20/30 mg) vs. inhaled cannabis (1,8/2,8/3,9% THC) vs. placebo; in subjects with wasting, significant increase in caloric intake under cannabis (all 3 doses) and dronabinol (10, 20 mg) vs. placebo (p<0.05); 30 mg dronabinol poorly tolerated in a subgroup; cognitive effects minor.

Intent-to-treat analysis showed no significant differences between cannabis extract, THC and placebo regarding appetite, quality of life or cannabinoid-related toxicity.

Multicentre phase III RCT (n=243 randomised; 164 completers); cannabis extract (CE, 2,5 mg THC + 1 mg CBD) and THC 2,5 mg vs. placebo orally 2×/day over 6 weeks in patients with tumour-associated anorexia-cachexia syndrome (CACS). Intent-to-treat analysis: no significant differences between groups for appetite (VAS baseline value 31/100 mm), quality of life (EORTC QLQ-C30 score 30/100) or cannabinoid-related toxicity. Increased appetite was reported by 73 % (CE), 58 % (THC) and 69 % (placebo). Study terminated early by independent data review board. CE well tolerated, but no therapeutic benefit demonstrable over placebo.

THC increased appetite in 13 of 18 evaluable cancer patients with anorexia and showed good tolerability.

Phase II study (n=18 evaluable) on THC 2,5 mg t.i.d. for cachexia/anorexia due to advanced tumor; 13/18 patients (72%) with improved appetite after 28 days; well tolerated at low doses; further studies needed for dose optimization.

Dronabinol significantly improved body fat percentage and symptom distress, but showed only non-significant trends for weight and prealbumin.

n=12 HIV patients with weight loss, dronabinol 5mg 2×daily vs. placebo (crossover); body fat +1% (p=0.04), symptom distress significantly reduced (p=0.04); weight gain +0.5kg (p=0.13, trend); high attrition (only 5/12 completed).

Dronabinol increased caloric intake and improved sleep only initially (days 1–8), with tolerance development upon repeated administration, but sustained mood improvement.

n=7 HIV-positive cannabis users; dronabinol 10 mg QID vs. placebo in 2×16-day inpatient phases; caloric intake significantly increased in the first 8 days, followed by selective tolerance development; mood improvement sustained over 16 days; no relevant cognitive or psychotropic side effects; daily dose >FDA recommendation necessary in HIV+ users.

In a subset of patients a clinically relevant weight gain and reduced appetite loss were observed, however with considerable study attrition and without a control group.

n=17 patients with advanced cancer disease and CACS, dose-controlled THC/CBD capsules (5–10 mg THC 2×daily); 3/17 (17,6%) achieved the primary endpoint goal (weight gain ≥10%); appetite loss symptoms significantly improved after cannabis treatment (p=0,05); methodologically limited by lack of a control group and high drop-out rate.

Narrative review on mechanisms and treatments of cancer cachexia; no primary effect measurements reported.

Narrative review on mechanisms and therapy of cancer cachexia; cannabis cannabinoids are mentioned as a potential appetite-stimulating treatment option, no systematic data extraction on cannabis-specific outcomes.