001IIIb       ↗IIIc 23 (+) (+) + (+) + + Werner 1999 [78] Abnobaviscum Fr ipl 1 × 75 mg/w No 3–8 w Pleural effusion (breast, others) 88%       ↗ 32 + + + – (+) (+) Stumpf 1994 [79] Helixor A, M or P ipl 100–1000 mg Yes repeatedly Pleural effusion (breast, others) 61% 11% 22%     18 + + +

(+) + + Friedrichson 1995 [80] Helixor A, M ip 100–1000 mg, 2/w Yes repeatedly Ascites (ovary, others) 70%       ↗ 12 (+) (-) + – (-) + I sc: subcutaneous, it: intratumoural, ipl: intrapleural, ip: intraperitoneal; iv: intravenous infusion; bw; body weight; w: week II CIN: cervical Combretastatin A4 cell line intraepithelial neoplasia. Stage: advanced, except in Portalupi 1995, and partly Schink 2006 and Finelly HDAC inhibitor 1998; plural effusion and ascites indicates treatment site III CR: complete, PR: partial remission, NC: no change, PD: progredient disease, QoL: quality of life, ↗: improved, ↘ impaired IIIa Especially physical functioning, role, fatigue, appetite IIIb Median values, comparable abdominal circumference

and symptom score or drained fluid before or during each GSI-IX paracentesis respectively IIIcTrend improvement in symptom score, especially abdominal pain, abdominal pressure, and waking up at night due to shortness of breath IV N: Number of participants V Concomitant conventional oncological cytoreductive therapies in some of the patients VI L Well-described patient characteristic and disease (diagnosis, stage, duration), prognostic factors M Outcome parameter relevant and well described N Well-described intervention O Concomitant

therapies well described P Outcome clearly described, temporal relationship between applied therapy and observed outcome precisely PAK5 described Q Selection of patients excluded + = adequately fulfilled, (+) = partly fulfilled, (-) = little fulfilled, – = not fulfilled Controlled studies The 19 RCTs [47–63] (Table 1) encompassed 2420 participants, 16 non-RCTs [49–53, 59, 64–72] (Table 2) encompassed over 6399 participants (the sample size of one control group was not published). Cancer sites studied were breast (n = 20), uterus (n = 4), ovary (n = 6), cervix (n = 4), and genital (n = 1). One RCT investigated malignant pleural infusion.