Table 3.

Characterization of the included studies

Reference	Study type	CA type/Intervention/arms	Endpoints	Outcomes
Balzarini et al. (2000)	RCT	Breast-CA arm A: RTX + Belladonna 7CH globules + X-ray globules arm B: RTX + placebo	1: severity of skin reaction associated with RTX 2: severity of skin reaction while RTX 3: severity of skin reaction post RTX (15/30 d after) AEs	1: No significant differences (nsd) in skin colour or hyperpigmentation, significant differences regarding temperature to the touch in 4 of 8 defined times (A < B: T3: p = 0.008, T4: p = 0.016, T6: p = 0.023, T7: p = 0.011), significant differences regarding oedema (A > B: T5 and T6: p = 0.025) 2: nsd 3: nsd AEs: 1 drop-out due to homeopathic exacerbation, 4 drop-outs due to the AE’s of radiation
Frass et al. 2015	RCT	Different types of CA, arm A: CTX or RTX + indiv. Homeopathy arm B: CTX or RTX	1: global health 2: subjective well-being 3: functioning scales 4: side effcts of CTX/RTX (EORTC QLQ-C30: function-, sympt- sclaes) AEs	1: nsd for global health (95% KI = 2.3, 13.0; p = 0.005) 2: significant differences favouring arm A (95% KI = 8.5, 21.0; p < 0.001) 3: significant differences favo***ring arm A regarding physical functioning (95% KI = 8.6, 18.4; p < 0.001), role functionig (95% KI = 0.4, 16.9; p = 0.004), cognitive functioning (95% KI = 7.7, 19.7; p < 0.001), social functioning (95% KI = 6.7, 20.4; p < 0.001), emotional functioning (95% KI = 8.0, 20.7; p < 0.001); significant differences favouring arm A regarding fatigue (95% KI =  − 24.7, − 12.4; p < 0.001), pain (95% KI =  − 23.8, − 10.1; p < 0.001), dyspnea (95% KI =  − 19.6, − 4.3; p = 0.002) and insomnia (95% KI =  − 15.6, − 0.9; p = 0.029) 4: significant differences favouring arm A ragarding appetite loss (95% KI =  − 17.1, − 2.7; p = 0.007), nsd regarding nausea & vomiting, obstipation or diarrhoea AEs: no AEs of the homeopathic treatment observed
Jacobs et al. (2005)	RCT	Breast-CA with HF arm A: single indiv. Homeopathy + placebo combination arm B: single placebo + combination Homeopathy (Hyland’s Menopause) arm C: single placebo + combination placebo	1: HF severity score 2: HF frquency (total number) 3: Kupperman Menopausal Index 4: QoL AEs	1: in a subgroup without tamoxifen significant differences to the disadvantage of arm B compared to arm A (95% KI -51.9, − 15.0; p < 0.001) and arm C (95% KI 6.2, 47.1; p = 0.01), no other significant differences in HF severity score 2: in a subgroup without tamoxifen significant differences to the disadvantage of arm B compared to arm A (p < 0.002) and arm C (p = 0.006), no other significant differences in HF frequency 3: nsd except for an increase of headache in arm B at 6 and 12 months (p = 0.040; p = 0.030) 4: significant differences not in terms of physical function (p = 0.1), but in general health favouring arm A and arm B over arm C (p = 0.02; p = 0.03) AEs: no AEs reported by the patients (pat.), increase of HF and headaches in arm B according to statistical analysis, overall incidence (any type, any grade) equally distributed between all arms
Pérol et al. (2012)	RCT	Breast-CA arm A: CTX, Cocculine, antiemetic therapy arm B: CTX + placebo, antiemetic therapy	1: CTX induced nausea and vomiting (CINV) in 1st CTX-cycle 2: CINV 2nd and 3rd CTX-cycle 3: treatment compliance AEs	1: nsd between both arms during 1st CTX-cycle according to FLIE-questionnaire or patient diaries 2: nsd between both arms except for significantly more vomiting episodes during 3rd cycle (assessed with patient diaries, p = 0.030) in favour of arm A 3: similar between arms considering patient diaries & count of remaining tablets AEs: no side effects related to the intervention drug
Sorrentino 2017	RCT	Breast-CA arm A: Arnica montana arm B: placebo	1: reduction in blood & serum volumes 2: duration of drainage 3: time until collected volume < 10 ml 4: self-evaluation of pain (VAS) 5: average time of hospitalization 6: bruises & hematomas / breast swelling 7: difference between volume collected on day 1 & volume on each of the following days 8: side effects	1: nsd in ITT-dataset (p = 0.60), significant reduction in blood & serum volumes in PP-dataset (p = 0.03) 2: neither ITT- nor PP- dataset shows significant differences (p = 0.7287, p = 0.8653) 3: neither ITT- nor PP- dataset shows significant differences (p = 0.8653, p = 0.6138) 4: nsd in VAS between both arms 5: no data reported 6: nsd regarding bruises & hematomas (p = 0.67) or breast swelling (p = 0.57) 7: significant differences in favour of arm A the PP-dataset on day 2 in the univariate model (p = 0.034) & regression modell (p = 0.033), also on day 3 in the regression modell (p = 0.0223) 8: no severe side effects, not correlated with homeopathic treatment
Thompson et al. 2005	RCT	Breast-CA with HF arm A: indiv. Homepathy arm B: placebo	1: activity & profile score 2: Menopausal Symptom Questionnaire 3: Hot flash severity & frequency 4: QoL + BreastCa-module 5: Hospital Anxiety & Depression Scale 6: satisfaction & perception of helpfulness 7: Glasgow Homeopathic Hospital Outcome Scale AEs	1: nsd in activity score (p = 0.17) or profile score (p = 0.13) 2: nsd in night sweat frequency, influence on sleep, days weat frequency or influence on daily functioning 3: no data reported 4: nsd regarding general health (p = 0.62) or QoL (p = 0.85) 5: nsd regarding anxiety and depression 6: significant differences favouring arm B (p = 0.01) 7: nsd AEs: 25% of pat. in both arms suffered AEs with only minor differences regarding aggravations, appearance of new symptoms, return of former symptoms
Frass et al. 2020a, b	RCT	NSCLC, arm A: indiv. homeopathy and CTX arm B: placebo and CTX Arm C: control	1: qol 2: survival 3: previous alternative treatment 4: attitude towards Homeopahy AEs	1: significant differences favoring homeopathy (p ≤ 0.001) after 9 and 18 weeks for physical, role, emotional and social functioning as well as fatigue, nausea and vomiting, dyspnoea, insomnia, appetite loss as well as constipation (p = 0.008; p = 0.005), significant differences only after 18 (and not 9) weeks in cognitive function (p = 0.113; p = 0.001), pain (p = 0.061; p < 0.001), diarrhoea (p = 0.590; p = 0.017) and financial difficulties (p = 0.134; p = 0.021) 2: significant differences favouring arm A in median mortality (A vs B 435 vs 257 days, p = 0.01; A vs C 228 days, p < 0.001; B vs C nsd) and 2-year mortality (A vs B 45.1% and 23.4%, p = 0.020; A vs C 13.5%, p < 0.001; B vs C nsd); significant differences regarding pat. who died within 2 years favouring arm A compared to arm C (p = 0.020), nsd between the other arms; significant differences regarding estimated survival time (A vs B (477 vs 352 days, p = 0.014), A vs C (274 days, p < 0.001), B vs C nsd) 3: nsd, mostly psychotherapy 4: former homeopathy treatment referred by practitioners (57.1% arm A, arm B 17.6%), pat. in arm B used homeopathy significantly more often without doctors’ recommendation (p = 0.039), expectaions of pat. in arm A was significantly lower (p = 0.010) AEs: no side effects related to the intervention drug
Heudel et al. 2019	RCT	Breast-CA, arm A: BRN-01 (Actheane®) arm P: placebo	1: HF scale 1st – 2nd visit 2: HF scale 1st – 3rd visist 3: compliance 4: safety & tolerance 5: QoL 6: satisfaction	1: nsd in HF scale after 4 weeks (p = 0.756) 2: nsd in HF scale after 8 weeks (p = 0.775) 3: compliance in arm A < arm P, but nsd (p = 0.606) 4: cases of joint pain and cholecystitis, not related to remedy 5: nsd in QoL, no statistical analysis was made 6: no major differences, no statistical analysis
Lotan et al. 2020	RCT	Breast-CA or risk reduction, post mastectomy & immediate breast reconstruction arm A: Arnica montana Bellis & perennis arm B: placebo	1: time to drain removal 2: opioid intake 3: QoL, quality of recovery 4: postoperative pain (VAS) 5: haemoglobin 6: cortisol levels AEs	1: time to drain removal significantly shorter in arm A (11.1 ± 6.1 days in arm A; 13.5 ± 6.4 days in arm B; p < 0.05), amputated breast weight & implant volume significantly lower in arm A (p < 0.001) 2: trend towards lower opioid intake in arm A, but nsd (p < 0.057) 3: nsd, no p value reported 4: nsd in VAS, no p value reported 5: nsd regarding hemoglobin, no p value reported 6: nsd in cortisol levels, no p value reported AES: no side effects related to the intervention drug
Karp et al. 2016	CT	Breast-CA Arm H: Aromatase inhibitor + Ruta graveolens & Rhus toxicodendron Arm C: AI only	1: joint pain 2: joint stiffness 3: morning & daytime intensity of stiffness 4: time to disappearance of stiffness 5: impact of pain on sleep (quality & quantity) 6: use of analgesics AEs	1: overall composite pain score significantly worse in arm C (p < 0.0001), as well as frequency (p = 0.0004), intensity (p = 0.0004) and number of sites (p = 0.0315) 2: nsd regarding the overall scores for joint stiffness p = 0.0567, joint stiffness worsened significantly more in arm C (p = 0.0141) 3: significantly better evolution of intensity of morning stiffness in arm H (p = 0.0198), nsd in daytime stiffness (p = 0.179) 4: significantly lesser time in arm H until disappearance of morning stiffness (p = 0.022) 5: lower impact of JP on sleep in arm H (p = 0.0083), no statistical analyses for patients whose pain never disturbed sleep 6: significant differences in frequency (p = 0.0034) and increase (p = 0.0076) of analgesic use AEs: no side effects related to the intervention drug
Steinmann et al. 2012	CT	Head & neck tumours, RTX/RCTX arm A: Traumeel S solution arm B: Sage tea (Salvia officinalis)	1: grade of oral mucosis 2: intraoral pain 3: QoL 4: xerostomia (difficulty in speech & eating) AEs	1: nsd regarding grade of oral mucosis 2: nsd regarding intraoral pain 3: nsd regarding QoL 4: significant difference in week 4 favouring arm A (no p-value reported) AEs: no information on side effects
Clover et al. 2002	Uncon-trolled pilot out-come study	Breast CA with Hot Flushes arm A: HF, no Breast-CA, homeopathy arm B: Breast-CA, homeopathy, no TMX arm C: Breast-CA, homeopathy, TMX	AEs	AEs: no information on side effects
Forner-Cordero et al. 2009	Pro-spective single-armed study	Breast-CA, post unilateral breast surgery & exhibited arm-lymphedema, oral Lymphomyosot + compression hosiery, kinesiotherapy & skin care	AEs	AEs: 8 of 17 patients with treatment- emergent AE s, four pat. discontinued treatment due to AEs (1 patient each with nycturia, hypertensive crisis, right hypochondrial pain, heartburn), further AEs reported were anxiety, constipation and dry mouth
Freyer et al. 2014	Pro-spective single-armed study	Different treatment-refractory types of CA, Ruta graveolens until tumor- or clinical progression	AEs	AEs: none of the AEs considered to be directly related to remedy
Schlappack 2004	Pro-spective single-armed study	Patients with Breast-CA and RTX-induced itching, Single dose of indiv. homeopathy	AEs	AEs: no information on side effects
Thompson et al. (2002)	Pro-spective single-armed study	Different types of CA, indiv. Homeopathic treatment	AEs	AEs: reactions of homeopathic remedies in 17/57 patents: aggravation of symptoms, development of old symptoms (reported as part of the healing), transient worsening of symptoms (settled on stop of remedy intake); withdrawal of homeopathic remedy was not necessary, 1 pat. was advised to stop treatment (acute blast phase of chronic myeloid leukaemia)
Thompson and Reilly 2003	Pro-spective single-armed study	BreastCA, oestrogen withdrawal, indiv. Homeopathic treatment	AEs	AEs: 7/40 patients reported new symptoms, 10 patients reported return of old symptoms, 1 patient with a difficult aggravation of symptoms which stopped after pausing the homeopathic treatment
Gartner et al. (2012)	Retro-spective single-armed study	Different types of CA, indiv. homeopathic treatment	AEs	AES: no information on side effects