Омела белая Viscum album Mistletoe
жүктеу/скачать 2.26 Mb.
|
- Бұл бет үшін навигация:
- Design
- Participants
- Interventions
- Outcomes
- Statistical methods
- Results
- Disease-free survival
MethodsObjectivesThe objective of this 5-year follow-up study is to analyze whether VaL therapy in addition to chemotherapy has an influence on the median disease-free survival time as well as the total frequency of relapses and metastases in patients with early stage breast cancer. DesignThis is a prospective non-interventional follow-up study of two patient groups after participation in a randomized clinical trial. None of the patients received VaL extract after the end of the chemotherapy. Ethical approval was obtained from Institute for Oncology and Radiology of Serbia. All patients provided written informed consent before commencing participation. ParticipantsBreast cancer patients in stages T1–3N0–2M0 treated at the Institute of Oncology and Radiology, National Cancer Research Centre of Serbia in Belgrade who received six consecutive cycles of CAF after surgery were included. For participation in the long term follow-up, the following inclusion criteria were obligatory: patients should have had 6 cycles of chemotherapy, should definitively not have had metastases before the chemotherapy began, and should not have refused to participate in the study. Two patients in the VaL group had an unknown metastatic status (M = x) before the chemotherapy began, and one patient in the control group did not give her consent for continued participation. Therefore, we included 28 of 30 patients of the VaL group and 29 of 30 patients of the control group in this analysis (see Fig. 1). The follow-up began in June 2006 and ended in May 2012. InterventionsAll patients have had CAF therapy administered in six cycles with a three-week interval between each cycle. The applied dose intensities (DI) of cyclophosphamide, Adriamycin, and 5-FU (DI in mean mg/m2 per week, ±standard deviation) were 160.5±5.6,16.1±0.6, and 160.5 ± 5.6, respectively, in the VaL group and 159.4±7.3, 15.9±0.7, and 159.4±7.3, respectively, in the control group. The results correspond to 98% of planned DI in the VaL group and 97% of planned DI in the control group. No other antineoplastic or immunomodulating therapies were applied during chemotherapy. All patients received antiemetic therapy with a single dose of ondansetron chloride 8 mg, dexamethasone 8 mg, and ranitidine 50 mg, respectively, administered prior to each CAF cycle. Patients randomly allocated to additional therapy with VaL received Iscador®M special, a fermented aqueous extract of VaL from apple tree (ratio of plant to extract = 1:5), manufactured by Weleda AG, Schwäbisch Gmünd, Germany. VaL comes in 1 mL ampoules for injection and each ampoule contains the fermented extract of 0.01, 0.1, 1, 2, or 5 mg of fresh extract of VaL, respectively, in isotonic saline solution. VaL was administered by subcutaneous injections of 1 mL into the upper abdominal region three times per week (e.g. Monday, Wednesday, Friday). The patients in the VaL group were instructed to inject themselves subcutaneously. The dosage of VaL was increased stepwise: 2 × 0.01 mg, 2 × 0.1 mg, 11 × 1 mg, 8 × 2 mg, remaining doses 5 mg. An average of 53.8 ± 2.6 injections with altogether 174.0 ± 26.6 mg of VaL per patient were administered in the VaL group. The control group did not receive additional VaL therapy to chemotherapy.
OutcomesOccurrence of relapse and/or metastasis was documented annually up to 5 years during the prescribed routine follow-up visits of the study centre. The results were documented in case report forms designed for this study. A deviation of ±2 months was tolerated for the annual visits. The follow-up for an individual patient ended with the occurrence of a relapse or a metastasis. Statistical methodsStatistical analysis (StatExact V9.0, WinStat V2012.1) included all participating patients. All results are of exploratory nature and may serve for hypothesis building or sample size calculation. The Mann-Whitney test, Fisher’s exact test, Kruskal-Wallis test, and t-test were used to check the balance of demographic and clinical baseline characteristics as well as for the therapies after chemotherapy. The disease-free survival curves were calculated by the Kaplan-Meier method and compared between study groups using a log-rank test (Cox-Mantel). ResultsAfter chemotherapy and VaL therapy ended, patients underwent other therapies, which may have influenced the disease-free survival rate. Therefore, other therapies were documented in both groups. The most frequent therapies were adjuvant radiotherapy (n = 37) and anti-hormonal therapy (tamoxifen; n = 32; Table 2). Both therapies were well balanced between the study groups and have been analyzed as separate subgroups (Figs. 3 and and4).4). Other therapies were trastuzumab (n = 4), goserelin (n = 2), docetaxel (n = 1), and letrozole (n = 1; Table 2). The latter therapies in total were also well balanced between the groups, but their frequency of application was too small to represent subgroups for an analysis. Disease-free survivalThe median disease-free survival time could not be calculated, because the highest probability for relapse or metastasis in 5 years was 28%. The disease-free 5-year survival rates were 6/28 and 8/29 patients in the VaL and the control groups, respectively (Fig. 2). The difference was not statistically significant (P = 0.551; Cox-Mantel log-rank test). The subgroup analysis of patients undergoing radiotherapy yielded 4/19 and 3/18 patients in the VaL and the control group, respectively (Fig. 3); the subgroup analyses of patients with anti-hormonal therapy yielded 4/18 and 4/14 patients in the VaL and control group, respectively (Fig. 4). None of the differences were statistically significant (Fisher’s exact test P = 0.792 and P = 0.659, respectively). |