Example Queries III

What helps against mucositis in cancer? (just selenium and curcumin)

	Outcome topic	Results during intervention	Results after intervention	Overall RoB judgment
Jahangard-Rafsanjani et al. (2013): The efficacy of selenium in prevention of oral mucositis in patients undergoing hematopoietic SCT: a randomized clinical trial	Selenium	Onset of mucositis after transplantation comparable in both selenium and placebo arm; p=0.81	Overall: Cumulative incidence (grade 1-4) comparable in both selenium arm (83.8%) and placebo arm (81.1%); p=0.76; grade 3-4 mucositis significantly lower in selenium arm (10.8%) compared to placebo arm (35.1%); p=0.013 (grade 4: 2x in placebo arm, 0x in selenium arm) Mean duration comparable (p=0.048), only duration of objective mucositis from grade 2 to 4 and back was significantly shorter in the selenium arm (3.6±1.84 days) than in the placebo arm (5.3±2.2 days); p=0.014	high risk
Laali et al. (2020): Effect of Selenium on Incidence and Severity of Mucositis during Radiotherapy in Patients with Head and Neck Cancer	Selenium	Significant difference for incidence of severe mucositis at week 3: selenium arm 9.8% vs. placebo arm 42.0% (p=0.017)	After 7 weeks no significant differences between the selenium arm and the placebo arm for: mean duration of oral mucositis (grade 1–4) (p=0.27) onset of oral mucosits (p =0.31) recovery (day after radiation completion (p=0.80) cumulative incidence of oral mucusitis (grade 1–4) (p=0.79) Severe oral mucositis (grade 3 or 4) was seen in 25 patients in the selenium arm and in 20 patients in the placebo arm. Addition: Development of oral mucositis in patients with selenium levels >65 mcg/l significantly delayed from baseline (p=0.04, no further explanation given)	high risk
Mansourian et al. (2015): The effect of "curcuma Longa" topical gel on radiation -induced oral mucositis in patients with head and neck cancer	Curcumin	Significant difference between intervention vs. placebo arm in mean (SD): intervention 3.7 (2.1) vs. placebo 7.9 (2.0); p < 0.001	NA	some concerns
Mansourian et al. (2015): The effect of "curcuma Longa" topical gel on radiation -induced oral mucositis in patients with head and neck cancer	Curcumin	Max. degree of mucositis (number (%) of patients): Grade 1: Intervention arm: 15 (78.9%), Placebo arm: 3 (16.7%) Grade 2: Intervention arm: 4 (21.1%), Placebo arm: 8 (44.4%) Grade 3: Intervention arm: 0 (0%), Placebo arm: 7 (38.9%) Grade 4: Intervention arm and Placebo arm: 0 Difference between arms in distribution of grades: p < 0.001 Time between T0 and onset of max. mucositis: no numbers given; p = 0.315 Incidence of max. mucositis (number (%)): 7 days: Intervention arm: 4 (21.1%), Placebo arm: 8 (44.4%) 14 days: Intervention arm: 6 (31.6%), Placebo arm: 4 (22.2%) 21 days: Intervention arm: 9 (47.4%), Placebo arm: 6 (33.3%)	NA	some concerns
Mix et al. (2015): Randomized phase II trial of selenomethionine as a modulator of efficacy and toxicity of chemoradiation in squamous cell carcinoma of the head and neck	Selenium	NA	Overall: No significant differences between arms (grade 3 intervention arm 2x, placebo arm 3x, no grade 4)	some concerns
... further results

What are side effects of cannabis? (arm-based!)

	Intervention	Side Effects / Interactions
Côté et al. (2016): Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial	Nabilon + all patients: additional administration of antiemetics (metoclopramide) and painkillers (acetaminophen (paracetamol), codeine, hydromorphone or transdermal fentanyl) possible Placebo + all patients: additional administration of antiemetics (metoclopramide) and painkillers (acetaminophen (paracetamol), codeine, hydromorphone or transdermal fentanyl) possible	No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83) No differences for sleepiness (p=0.32), anxiety (p=0.92) and xerostomia (p=0.83)
Fallon et al. (2017) I: Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies	Sativex Placebo	Overall 68% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=64 (32.2%), of which somnolence n=18 (9%), dizziness n=15 (7.5%), nausea n=10 (5%) 2 severe side effects associated with intervention: 1x constipation (with 360mg/day morphine equivalents), 1x moderate disorientation and somnolence on day 4 (with 2.5 daily sprays of Sativex) None of the deaths related to intervention Overall 64% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=41 (20.7%), of which somnolence n=6 (3%), dizziness n=6 (3%), nausea n=8 (4%) 2 severe side effects associated with intervention: 1x constipation (with 360mg/day morphine equivalents), 1x moderate disorientation and somnolence on day 4 (with 2.5 daily sprays of Sativex) None of the deaths related to intervention
Fallon et al. (2017) II: Sativex oromucosal spray as adjunctive therapy in advanced cancer patients with chronic pain unalleviated by optimized opioid therapy: two double-blind, randomized, placebo-controlled phase 3 studies	Sativex Placebo	Part A Overall 60% at least one event, assessed as probably intervention-associated with frequency ≥ 5%: Total n=128, 31.7%, somnolence (n=42, 10.4%), nausea (n=21, 5.2%) and dizziness (n=21, 5.2%) Part B Overall 72% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=16, 15.5%; somnolence (n=6, 5.8%) More than twice as many patients in Sativex arm discontinued study due to side effects (n=14, 13.6% vs. n=6, 5.8%); no statistical comparison given) None of the deaths related to intervention Part A Overall 60% at least one event, assessed as probably intervention-associated with frequency ≥ 5%: Total n=128, 31.7%, somnolence (n=42, 10.4%), nausea (n=21, 5.2%) and dizziness (n=21, 5.2%) Part B Overall 62% at least one event; assessed as probably intervention-associated with frequency ≥ 5%: Total n=12, 11.7%; somnolence n=0
Grimison et al. (2020): Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial	THC:CBD Placebo	Moderate or severe cannabinoid-related side effects in intervention arm and placebo arm (31% vs. 7%, p=0.002): Significant differences for sedation (19% vs. 4%, p=0.002) and dizziness (10% vs. 1%, p=0.03) No differences for disorientation (p=0.5) and anxiety (p=1.00) No cannabinoid-related serious adverse events reported 83% of the participants preferred cannabis over placebo and 15% had a preference for placebo (p<0.001) Moderate or severe cannabinoid-related side effects in intervention arm and placebo arm (31% vs. 7%, p=0.002): Significant differences for sedation (19% vs. 4%, p=0.002) and dizziness (10% vs. 1%, p=0.03) No differences for disorientation (p=0.5) and anxiety (p=1.00) No cannabinoid-related serious adverse events reported 83% of the participants preferred cannabis over placebo and 15% had a preference for placebo (p<0.001)
Jatoi et al. (2002): Dronabinol Versus Megestrol Acetate Versus Combination Therapy for Cancer-Associated Anorexia: A North Central Cancer Treatment Group Study	Megestrol Acetate Dronabinol Megestrol Acetate + Dronabinol	Impotence in 18 % of men; vomiting; fluid retention; confused thinking; drowsiness; loss of coordination; inappropriate behavior Impotence in 4% of men; vomiting; fluid retention; confused thinking; drowsiness; loss of coordination; inappropriate behavior Impotence in 14% of men; vomiting; fluid retention; confused thinking; drowsiness; loss of coordination; inappropriate behavior
... further results

How does cannabis influence nausea and vomiting in cancer patients?

	Results during intervention	Overall RoB judgment
Côté et al. (2016): Improving Quality of Life With Nabilone During Radiotherapy Treatments for Head and Neck Cancers: A Randomized Double-Blind Placebo-Controlled Trial	Over the course of the intervention and after: no difference for nausea (p=0.7105) or antiemetic consumption (p=0.6124) between arms	some concerns
Grimison et al. (2020): Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial	Results after 2 cycles, after switching to the other arm: Advantage for intervention arm for percentage for CR (p=0.04), for scales "no vomiting" (p=0.05), "no emergency medication" p=0.04), "no significant nausea" (p=0.03), mean and maximum number of vomiting per day (p=0.003, p=0.001), mean/maximum nausea values (p's<0.001). No difference for complete response and "no significant nausea" (p=0.12)	high risk
Grimison et al. (2020): Oral THC:CBD cannabis extract for refractory chemotherapy-induced nausea and vomiting: a randomised, placebo-controlled, phase II crossover trial	Results after 2 cycles, after switching to the other arm: Significant advantage for intervention arm (25%) compared to placebo arm (14%): RR=1.77; 90% CI=1.12,2.79; p=0.041.	high risk
Johnson et al. (2010): Multicenter, double-blind, randomized, placebo-controlled, parallel-group study of the efficacy, safety, and tolerability of THC:CBD extract and THC extract in patients with intractable cancer-related pain	No significant differences between THC:CBD arm/THC arm and placebo arm	high risk
Strasser et al. (2006): Comparison of orally administered cannabis extract and delta-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled (…)	Overall Improvement but without significant differences between arm (p=0.367)	high risk