A total of 32 patients with stage Ib/II gastric cancer, eligible for adjuvant oral doxifluridine treatment, were enrolled into this clinical trial. Three of the enrolled patients, one from the treatment group and two from the control group, were drop outs because they retrieved the informed consent.
No significant differences were observed in age, sex, height, weight, blood pressure, pulse rate, type of operation (total gastrectomy or distal gastrectomy) and pathologic classifications between the two groups (Table
). In both groups, the number of male patients was significantly higher. There were 28 patients in stage Ib and only one patient in stage II.
Demographic and pathologic data (SD= standard deviation; BP= Blood pressure, number of drop out patients in
Except 3 QoL parameters (pain, p = 0.038; eating restrictions, p = 0.037; hair loss, p = 0.023) and basophiles (p = 0.0315) baseline of QoL, immunological parameters, hematology and liver function tests were not different between the groups (Tables
, , , ).
QoL-Questionnaires: difference between treatment group (aVQ) and control group by independent t-test and result of the repeated measured analysis of variance (ANOVA, influence of treatment)
Immunological parameters: difference between treatment group (aVQ) and control group by independentt-test and result of the repeated measured analysis of variance (ANOVA, influence of treatment)
IL-2 mean values and standard deviation (SD): difference between treatment group (aVQ) and control group of the 4 visits by independent t-test
Routine laboratory parameters: mean difference and standard deviation (SD) between treatment group (aVQ) and control group by independent t-test and result of the repeated measured analysis of variance (ANOVA, influence of treatment)
Repeated analysis of variance (ANOVA) of the quality of life scales QLQ-C30 and QLQ-STO22 revealed a strong improvement of the “Global Health Status” (p = 0.0098) in the intervention group (Table
). The Global Health Status is a sum parameter of 2 questions of the QLQ-C30 questionnaire with a broader range (range = 6) than the other 28 questions (range
= 3), which allows a more precise judgment of the patients situation regarding the overall health and quality of life status. All other function and symptom scales of the QLQ-C30 and the stomach cancer module QLQ-STO22 did not show a significant effect of the intervention. The analysis of variance for the hematologic variables showed significantly higher WBC counts (p = 0.0101) and eosinophil counts (p = 0.0036) in the intervention group. For the immunologic variables repeated measured ANOVA detected no significant differences in CD16+
and CD 19+
lymphocytes, TNF-alpha and IL-2 between control group and intervention group (Table
). Anyhow, the IL-2 mean values are considerably higher in the treatment group (Table
) with an extreme coefficient of variation. Applying the non-parametric rank sum test for the IL-2 values a significant difference results (F = 4.4794; p = 0.0433). Also the IL-2 median at visit 3, but not at the other visits, was significantly higher in the intervention group compared to the control group (Table
, p=0.034, two sided Mann-Withney U
Mean alkaline phosphatase (ALK) values were higher in the in the treatment group (visit 2, 3, 4, Table
). Anyhow, a significant influence of the mistletoe treatment on the ALK values could not be confirmed by ANOVA (F = 2.6545, p = 0.1145). Increase of ALK is a known side-effect of doxifluridine therapy.
The number of adverse events was similar in the control group (n = 96) and the treatment group (n = 92). Except 2 serious adverse events (SAE’s), 1 case of post-operative bleeding and 1 case of an acute infection, both in the treatment group and 1 AE with severe degree (itching at injection site, treatment group) all AE´s were mild or moderate. The SAE’s were judged as not related to the study medication. In the treatment group 26 of the 92 adverse events had at least a possible relationship to the mistletoe treatment. 80% (21 cases) of them were related to reactions at the injection site like local pain, itching, rash or urticaria. The others were 1 case of chest pain, 1 case of myalgia, 1 case of dizziness and 1 case of diarrhea. In the control group 20 cases of diarrhea (21% of the 96 cases) were recorded. The difference in diarrhea (6.7% in the treatment group, 50% in the control group, p = 0.014) was statistically significant. All recorded cases of diarrhea had a mild degree but in 3 patients of the control group the symptoms persisted until the end of the study.