Омела белая Viscum album Mistletoe
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- Бұл бет үшін навигация:
- Baseline data of the patient groups
- Quality of life during chemotherapy
- Neutropenia during chemotherapy
- Adverse events related to IMS injections
- Discussion
ResultsRecruitment, participant flow, assessment, and numbers analysedFrom 14 December 2005 to 15 February 2007 a total of 123 breast cancer patients were prescribed CAF and assessed for eligibility at the study centre IORS. 28 patients were not included and 95 patients were included and randomized into 3 groups: CAF and IMS (n = 30), CAF and another mistletoe preparation (n = 34), and CAF without additional therapy (n = 31). One patient in the control group was withdrawn from further CAF therapy after three cycles of CAF because of heart disease (Fig. 1). Detailed flow chart of the patient disposition. The EORTC-QLQ-C30 was evaluable for 99.5% (209 of 210) of visits in the IMS group, and for 97.2% (211 of 217) of visits in the control group. The neutrophil count was assessed at 99.5% (209 of 210) of visits in the IMS group and 98.2% (213 of 217) of visits in the control group. Baseline data of the patient groupsThe IMS group and the control group did not differ significantly regarding age, tumour stage, body mass index, physical status, vital signs, previous diseases, EORTC-QLQ-C30 scores (Table 1). No neutropenia was detected at baseline. Quality of life during chemotherapyDuring chemotherapy with CAF a deterioration of quality of life occurred in all 15 EORTC-QLQ-C30 scores in the control group and in six scores in the IMS group. A clinical relevant deterioration of at least 5 points was found in eight scores of the control group and in two scores in the IMS group (Table 3). The most pronounced deteriorations were observed for nausea/emesis (17.2 score points) and fatigue (8.2) after the 2nd cycle of CAF and insomnia (13.1) and diarrhoea (11.9) after the 3rd cycle. In the adjusted analyses, mean differences from baseline were compared between the two groups for each EORTC-QLQ-C30 score: All 15 comparisons favoured the IMS group, 12 comparisons showed significant differences with p-values ranging from 0.017 to <0.001. Clinically relevant differences of at least 5 points favouring the IMS group were observed for nine EORTC-QLQ-C30 scores (Table 2). In descriptive analyses, the differences from baseline for each score at each of the six follow-up assessments were compared between the two groups: 86 out of 90 differences favoured the IMS group, while four differences favoured the control group (Fig. 2). Furthermore, the maximum between-group difference for each EORTC-QLQ-C30 score during follow-up was analysed: All 15 differences favoured the IMS group: maximum differences of at least 15 points were found in four scores (Role Function, Social Function, Pain, and Insomnia), 10–15 point differences were found in five scores (Global Health, Emotional function, Constipation, Diarrhoea, Appetite loss), and differences <10 points were found in the remaining six scores.
Neutropenia during chemotherapyNeutropenia (<1,000/μl) was detected three times in three different patients of the IMS group and nine times in eight different patients of the control group. The patients with neutropenia are comparable across the groups (Table 3). Odds ratio for the proportion of patients with neutropenia in IMS group vs. control group was 0.32 (95% confidence interval 0.08–1.35). Using Fisher’s exact test according to the sequential rejective Holm procedure, a trend (p = 0.182) towards less neutropenia in the IMS group was found. Adverse events related to IMS injectionsLocalized skin reactions to IMS exceeding 5 cm diameter occurred in six patients. The frequency of these reactions was 0.49% (eight reactions in 1,618 injections). No other adverse events related to IMS occurred. DiscussionThis randomized pilot study assessed quality of life (EORTC-QLQ-C30) and neutropenia in early breast cancer patients undergoing CAF chemotherapy. Patients receiving IMS in addition to CAF had significantly better quality of life and showed a trend towards less neutropenia, compared to patients receiving CAF alone. IMS therapy was well tolerated. Strengths of this study include a high recruitment rate, detailed assessments of therapy implementation, high therapy compliance, and very low dropout rates. Since 83% of eligible patients were included and randomized, the results of this study would seem to be generalizable to breast cancer patients (T1–3N0–2M0) receiving CAF without any other concomitant therapies. Due to the open-label design, the study cannot distinguish between direct drug effects on quality of life and possible indirect effects from therapy expectations, therapy administration etc. in the IMS group. This is a general limitation to all mistletoe studies: mistletoe injections frequently cause local reactions at the injection site, elevated body temperature and flu-like symptoms. These symptoms cease within hours or days after exposure and may recur on repeated injections. Therefore, patients and physicians can easily guess if mistletoe extracts are administered. This was confirmed in a double-blind study, where all patients in the mistletoe group as well as their physicians were unblinded.16 A pseudo-placebo causing the same combination of time-limited symptoms—without specific effects on quality of life—has not yet been constructed. Generally, medication trials are blinded to separate pharmacological effects from placebo effects. However, the lack of blinding may not necessarily have had relevant effects on the results of this study: An updated Cochrane review of randomised trials comparing placebo to no treatment found no significant placebo effects on eight out of ten evaluable indications, small effects on self-reported pain and moderate effects on phobia. Even these effects might have been confounded by biases.22–24 This study was designed as a pilot study, and the limited sample size of 30 patients per group does not allow for hypothesis confirmation. Nevertheless significant differences in 12 of 15 EORTC-QLQ-C30 scores favouring the IMS group were found. Nine of these scores showed a clinically relevant difference of at least 5 points. The latter scores include pain, nausea, emesis and insomnia, which are highly relevant symptoms in patients during chemotherapy with CAF. An important problem which may occur during chemotherapy with CAF is neutropenia. Neutropenia is the limiting factor for a continuing chemotherapy and may be harmful to the patients. This study is the first randomized trial providing data on the incidence of CAF-induced neutropenia during additive therapy with IMS. A trend towards less neutropenia in the IMS group was found. This should be further investigated in confirmatory studies with adequate sample size. It is recommended to include measurements of neutrophils on day 7, 9 and day 11 after chemotherapy in order to assess the nadir of the neutropenia during CAF therapy. Future studies of mistletoe effects on quality of life in cancer patients undergoing chemotherapy should also include specific instruments to assess cancer-related fatigue and pain. In our study the effects of IMS on quality of life increased over time with the largest effects observed at the last follow-up visit. A longer follow-up period of 6–12 months might show additional long term benefits of IMS therapy.
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