Table 1.
Characteristics of included studies (first RCTs, then NRSIs). Further information (therapy duration, baseline fatigue score,
source of funding, mistletoe extract application form) is shown in Table S3
| First author, publication year; country*; reference | Study design | Participants at baseline; included in fatigue-analysis; mean age | Cancer type | Intervention | Fatigue measure | Adverse effects | ||
|---|---|---|---|---|---|---|---|---|
| Verum | Control | Verum | Control | |||||
| Bar-Sela, 2013; IL; [29] | RCT, single-center, open-label | 33; 27; 63.0 | 39; 28; 62.0 | Lung cancer (NSCLC) – inoperable IIIa, IIIb or IV | Iscador Qu; chemotherapy | Chemotherapy | EORTC QLQ-C30 | 5 patients; local reaction at injection site; CTCAE (V3.0) grade 1–2 |
| Büssing, 2008; DE; [30] | RCT, multi-center, open-label | 32; 32; 54.7 | 33; 33; 54.7 | Breast cancer | Iscador M Spezial; chemo-, radiotherapy | Chemo-, radiotherapy | EORTC QLQ-C30 | 13/1,000 doses; chills, fever; CTCAE (V3.0) grade 1–2 |
| Grah, 2010; DE; [25] | RCT, single-center, open-label | 26; 25; 64.3 | 24; 24; 62.0 | Lung cancer (NSCLC), IIIb or IV | Iscador Qu Spezial; chemotherapy | Chemotherapy | EORTC QLQ-C30 | 1.5/1,000 doses; hematoma at injection site, fever < 39 °C; heavy legs; CTCAE (V3.0) grade 1 |
| Kim, 2012; KR; [26] | RCT, single-center, open-label | 16; 15; 53.8 | 16; 14; 54.9 | Gastric cancer Ib or II | Abnobaviscum Q; waiting for chemotherapy | Waiting for chemotherapy | EORTC QLQ-C30 | 25/1,000 doses; local reaction at injection site, chest pain, myalgia, dizziness, diarrhea |
| Longhi, 2014; IT; [35] | RCT, single-center, open-label | 9; 9; 28.0 | 11; 11; 39.0 | Osteosarcoma after second relapse | Iscador P | Etoposide | EORTC QLQ-C30 | 1.4/1,000 doses; local reaction at injection site, hypotension; CTCAE (V3.0) grade 1 |
| Piao, 2004; CN; [21] | RCT, multi-center, open-label | 118; 115; 52.6 | 115; 110; 51.7 | Breast, ovarian cancer, NSCLC | Helixor A; chemotherapy | Lentinan chemotherapy | TCM | 7 pats.: rubor/pruritus at injection site 4 pats.: fever 1 pat.: angioedema |
| Semiglasov, 2004; RU, UA, BG; [31] | RCT, multi-center, blinded | 65; 65; 44.6 | 66; 66; 43.5 | Breast cancer, pT1-3, pN0-N + , M0 | Lektinol; chemotherapy | Placebo, chemotherapy | GLQ-8 | 12 patients with local reaction at injection site |
| Semiglazov, 2006; RU, UA, BG; [32] | RCT, multi-center, blinded | 176; 169; 46.4 | 176; 168; 45.9 | Breast cancer, pT1-3, pN0-N + , M0 | Lektinol; chemotherapy | Placebo, chemotherapy | GLQ-8 | 31 patients with local reaction at injection site |
| Steuer-Vogt, 2006; DE; [27] | RCT, multi-center, open-label | 200; 162; 55.0 | 199; 162; 55.0 | Head and neck cancer, T1-4, N0-3, M0 | Eurixor; surgery, chemo-, radiotherapy | Surgery, chemo-, radiotherapy | EORTC QLQ-C30 | 98 patients with rubor and prurigo; 6 patients with myalgia, insomnia, fever < 39 °C |
| Tröger, 2009; RS; [15] | RCT, single-center, open-label | 30; 30; 48.4 | 31; 31; 50.8 | Breast cancer, pT1-3, pN0-2, M0 | Iscador M Spezial; chemotherapy | Chemotherapy | EORTC QLQ-C30 | 4.9/1,000 doses; local reaction at injection site |
| Tröger, 2014a; RS; [33] | RCT, single-center, open-label | 34; 32; 50.4 | 31; 29; 50.8 | Breast cancer, pT1-3, pN0-2, M0 | Helixor A; chemotherapy | Chemotherapy | EORTC QLQ-C30 | 28/1,000 doses; local reactions at inj. site, allergic rhinitis; CTCAE (V3.0) grade 1–3 |
| Tröger, 2014b; RS; [34] | RCT, single-center, open-label | 110; 96; 65.0 | 110; 72; 61.0 | Pancreatic cancer, loc. advanced or metastatic, III/IV | Iscador Qu Spezial; best support. care | Best supportive care | EORTC QLQ-C30 | 67 patients; local reaction at injection site |
| Beuth, 2008; DE; [40] | NRSI, multi-center, open-label, retrospective | 227; 167; 55.1 | 514; 514; 54.6 | Breast cancer | Helixor M, A, P; radio-, chemo-, hormone therapy | Radio-, chemo-, hormone therapy | Clinician reported | 0.22/1,000 doses; local reaction at injection site, flu-like symptoms, generalized reaction |
| Friedel, 2009; DE, CH; [41] | NRSI, multi-center, open-label, retrospective | 433; 261; 57.2 | 387; 145; 62.8 | Colorectal cancer, primary, non-metastatic I-III | Iscador Qu, M, P, conventional therapy | Conventional therapy | Clinician reported | 100 pats. with local reaction at injection site; 10 pats. with low-grade fever, dizziness, fatigue, depression, tinnitus, nausea, acute allergic reaction; CTC (V2.0) grade 1–2 |
| Fritz, 2018; DE; [43] | NRSI, multi-center, open-label, retrospective | 151; 23; 55.5 | 453; 77; 55.7 | Breast cancer, any stage | Any mistletoe extract, radio-, chemo-, hormone ther | Radio-, chemo-, hormone therapy | EORTC QLQ-C30 | not reported |
| Loewe-Mesch, 2008; DE; [36] | NRSI, single-center, open-label, prospective | 39; 33; 47.5 | 43; 33; 47.5 | Breast cancer, pT1-3, N0-N2; M0 | Iscador M Spezial, chemotherapy | Chemotherapy only | EORTC QLQ-C30 | 24 patients with local reaction at injection site |
| Matthes, 2010; DE, CH; [42] | NRSI, multi-center, open-label, retrosepctive | 201; 182; 58.2 | 195; 124; 63.7 | Pancreatic cancer, any stage | Any Iscador, chemotherapy | Chemotherapy | Clinician reported | 45 pats. with local reaction at injection site; 3 pats. with low grade fever, immune intolerance, fatigue; CTC (V2.0) grade 1–3 |
| Oei, 2020; DE; [24] | NRSI, single-center, open-label, retrospective | 129; 89; 56.4 | 190; 124; 60.7 | Breast cancer, primary, non-metastasized | Anthroposophic mistletoe extracts, conventional therapy | Conventional therapy | EORTC QLQ-C30 | not reported |
| Schmidt, 2007; DE; [44] | NRSI, multi-center, open-label, retrospective | 710; 400; 53.0 | 732; 280; 57.0 | Breast cancer, stage I-III | Any Iscador, radio-, chemo-, hormone ther | Radio-, chemo-, hormone therapy | Clinician reported | 123 pats. with local reaction at injection site; 6 pats. with nausea, bacterial skin infection, increased neurodermatitis, fatigue, hyperactivity, diarrhea; CTC (V2.0) grade 1–2 |
| Schumacher, 2003; DE; [45] | NRSI, multi-center, open-label, retrospective | 219; 100; 60.0 | 470; 116; 64.0 | Breast cancer, primary, non-metastasized | Eurixor, radio-, chemo-, hormone therapy | Radio-, chemo-, hormone therapy | Clinician reported | 3.6/1,000 doses; local reaction at injection site, fever; CTC (V2.0) grade 1–2 |
*country abbreviations according to ISO: IL, Israel; DE, Germany; KR, South Korea; IT, Italy; CN, China; RU, Russia; UA, Ukraine; BG, Bulgaria, RS, Serbia; CH, Switzerland