- Email: [email protected]
Intravesical mistletoe plant extract in patients with non muscle invasive bladder Cancer - a phase III efficacy study – current status
Abstracts / Phytomedicine 22 (2015) S27–S30
Keywords: Viscum album, dendritic cells, tumour microenvironment doi: 10.1016/j.phymed.2015.05.060
S29
Intravesical mistletoe plant extract in patients with non muscle invasive bladder Cancer - a phase III efficacy study – current status Jürgen Eisenbraun ∗ Abnoba GmbH, Pforzheim, Germany
Is mistletoe therapy indicated to reduce cancer-related fatigue and insomnia in cancer patients? – a review Matthias Kröz a,b,c,d,∗, Arndt Büssing c, Marcus Reif e, Danilo Pranga a, Friedemann Schad a,b, Roland Zerm a,b, Harald Matthes a,b, Matthias Girke a,b a Research
Institute Havelhöhe (FIH), Berlin, Germany of Internal Medicine, Havelhöhe Hospital, Berlin, Germany c Institute of Integrative Medicine, University Witten/Herdecke, Germany d Institute of Social Medicine, Epidemiology, Health Economics, Charité University Medicine Berlin, Germany e Institute of Clinical Research, Berlin, Germany b Department
∗
Corresponding author. Tel.: +49 30 36501248. E-mail address: [email protected]
Introduction: Over the last decade Cancer-related Fatigue (CRF) has become a major issue in oncology. Fatigue is experienced by 70–90% of all patients receiving chemotherapy or with metastasized conditions and persists even after 5–10 years in 17–34% of breast cancer survivors. The best evidence for the treatment of CRF is available for exercise training and cognitive behavioral sleep- and mindfulness-based-interventions. With the growing evidence that concomitant mistletoe (MT) treatment with chemotherapy can reduce side-effects and improve health-related quality of life, CRF moved into the focus of MT research. With this review we evaluate the evidence of MT-therapy in the reduction of CRF. Methods: We conducted a literature review in Pubmed and found 68 articles with the research term ‘mistletoe AND quality of life’ and 13 on ‘mistletoe AND fatigue’. We selected all available randomizedcontrolled trials (RCT) comparing MT to placebo- or comparative treatment under chemo- and/or radiotherapy, or MT vs. best supportive care which used questionnaires including fatigue- and insomniacapturing items or scales. Results: We found ten RCTs capturing fatigue, tiredness and insomnia or sleep quality. Seven used the EORTC QLQ C30, two the Global Quality of Life Scale (GLQ) and one the Traditional Chinese Medicine scale (TCM). Four studies were conducted on breast cancer and one each on non-small cell lung cancer (NSCLC), pancreatic cancer, osteosarcoma, stomach, and head-neck cancer. One paper dealt with breast cancer, NSCLC and ovarian cancer. All studies were conducted with single items or three item scales which do not meet the standard criteria measuring CRF or chronic insomnia. In six of the ten studies MT reduced fatigue or tiredness significantly and in six out of nine MT improved sleep quality (three on breast cancer, one on osteosarcoma, one on pancreatic cancer, and one mixed study). Conclusion: the lack of evidence of CRF- and insomniaimprovements measured with multidimensional standard-scales as a primary outcome in published mistletoe studies there is a growing indication that Viscum album can contribute to a reduction of fatigue and insomnia in cancer patients undergoing chemotherapy. These results therefore need to be confirmed in rigorously conducted trials with the primary outcome CRF and insomnia. Keywords: cancer-related fatigue, insomnia, mistletoe, healthrelated quality of life, review doi: 10.1016/j.phymed.2015.05.061
∗
Tel.: +49 7231 315050; fax: +49 7231 358714. E-mail address: [email protected] Purpose: To determine safety and efficacy of intravesical instillations of mistletoe extract after transurethral resection of non muscle invasive bladder tumours. Methods: In this randomized, open-label, active-controlled, prospective, multinational phase III confirmative study the efficacy of intravesical instillations of abnobaVISCUM 900 and Mitomycin C (MMC) is compared. Patients with completely resected non muscle invasive bladder cancer stage Ta with an intermediate-risk classification according the European Association of Urology (EAU) guideline (update 2013) and with one immediately post-operative MMC 40 mg intravesical instillation will be included in this study. Eligible patients will be allocated to 2 treatment groups in a 1:1 ratio. The study period comprises 12 months of treatment and a follow up period of 12 months. All patients will receive 6 weekly intravesical instillations (induction therapy) and a maintenance therapy up to the end of the first year. The maintenance instillations will comprise one instillation every 6 weeks in the abnobaVISCUM arm and in the MMC arm one instillation with 40 mg every 12 weeks, in total 13 resp. 10 instillations up to the end of the first year. The follow up visits in the second year will take place every 12 weeks. Primary efficacy criterion is time to tumour recurrence, the secondary objective is to evaluate the safety of abnobaVISCUM 900 compared to MMC monotherapy. Statistically a two-stage procedure according to Bauer and Köhne will be performed. Results: The current sample size calculation for Stage I and II is 546 patients for both arms. Currently 31 centers in Germany and 1 in Egypt are contracted. This is thought to be adequate for the planned recruitment. Regulatory requirements including the necessary ethical votes are fulfilled, the study received a recommendation of the AUO (AB 40/11, Arbeitsgemeinschaft Urologische Onkologie [Urological Oncology Study Group], part of the Deutsche Krebsgesellschaft e.V. [German Cancer Society]. Recruitment of patients has been started. Keywords: bladder cancer, mistletoe, intravesical instillation, Phase III Clinical Trial EudraCT No.: 2013-003446-16. ClinicalTrials.gov Identifier: NCT02106572 doi: 10.1016/j.phymed.2015.05.062 Palliative mistletoe therapy in pancreatic cancer patients undergoing first-line chemotherapy (PALM-PAN)
Marcus Reif ∗, Alexandra Lemche Society for Clinical Research, Berlin, Germany ∗
Corresponding author. Tel.: +49 30 31574431. E-mail address: [email protected]
Purpose: Pancreatic cancer (PaCa) is a fatal disease with an extremely poor prognosis. Most PaCa patients die within the first year after diagnosis, and only 6% are alive after five years. Over the past decade PaCa death rates slowly increased, in contrast to the downward trend for most other major cancer sites. The lack of progress in primary prevention and early diagnosis as well as the merely modest effects of novel chemotherapy (CTx) regimens underscore the need
Keywords: Viscum album, dendritic cells, tumour microenvironment doi: 10.1016/j.phymed.2015.05.060
S29
Intravesical mistletoe plant extract in patients with non muscle invasive bladder Cancer - a phase III efficacy study – current status Jürgen Eisenbraun ∗ Abnoba GmbH, Pforzheim, Germany
Is mistletoe therapy indicated to reduce cancer-related fatigue and insomnia in cancer patients? – a review Matthias Kröz a,b,c,d,∗, Arndt Büssing c, Marcus Reif e, Danilo Pranga a, Friedemann Schad a,b, Roland Zerm a,b, Harald Matthes a,b, Matthias Girke a,b a Research
Institute Havelhöhe (FIH), Berlin, Germany of Internal Medicine, Havelhöhe Hospital, Berlin, Germany c Institute of Integrative Medicine, University Witten/Herdecke, Germany d Institute of Social Medicine, Epidemiology, Health Economics, Charité University Medicine Berlin, Germany e Institute of Clinical Research, Berlin, Germany b Department
∗
Corresponding author. Tel.: +49 30 36501248. E-mail address: [email protected]
Introduction: Over the last decade Cancer-related Fatigue (CRF) has become a major issue in oncology. Fatigue is experienced by 70–90% of all patients receiving chemotherapy or with metastasized conditions and persists even after 5–10 years in 17–34% of breast cancer survivors. The best evidence for the treatment of CRF is available for exercise training and cognitive behavioral sleep- and mindfulness-based-interventions. With the growing evidence that concomitant mistletoe (MT) treatment with chemotherapy can reduce side-effects and improve health-related quality of life, CRF moved into the focus of MT research. With this review we evaluate the evidence of MT-therapy in the reduction of CRF. Methods: We conducted a literature review in Pubmed and found 68 articles with the research term ‘mistletoe AND quality of life’ and 13 on ‘mistletoe AND fatigue’. We selected all available randomizedcontrolled trials (RCT) comparing MT to placebo- or comparative treatment under chemo- and/or radiotherapy, or MT vs. best supportive care which used questionnaires including fatigue- and insomniacapturing items or scales. Results: We found ten RCTs capturing fatigue, tiredness and insomnia or sleep quality. Seven used the EORTC QLQ C30, two the Global Quality of Life Scale (GLQ) and one the Traditional Chinese Medicine scale (TCM). Four studies were conducted on breast cancer and one each on non-small cell lung cancer (NSCLC), pancreatic cancer, osteosarcoma, stomach, and head-neck cancer. One paper dealt with breast cancer, NSCLC and ovarian cancer. All studies were conducted with single items or three item scales which do not meet the standard criteria measuring CRF or chronic insomnia. In six of the ten studies MT reduced fatigue or tiredness significantly and in six out of nine MT improved sleep quality (three on breast cancer, one on osteosarcoma, one on pancreatic cancer, and one mixed study). Conclusion: the lack of evidence of CRF- and insomniaimprovements measured with multidimensional standard-scales as a primary outcome in published mistletoe studies there is a growing indication that Viscum album can contribute to a reduction of fatigue and insomnia in cancer patients undergoing chemotherapy. These results therefore need to be confirmed in rigorously conducted trials with the primary outcome CRF and insomnia. Keywords: cancer-related fatigue, insomnia, mistletoe, healthrelated quality of life, review doi: 10.1016/j.phymed.2015.05.061
∗
Tel.: +49 7231 315050; fax: +49 7231 358714. E-mail address: [email protected] Purpose: To determine safety and efficacy of intravesical instillations of mistletoe extract after transurethral resection of non muscle invasive bladder tumours. Methods: In this randomized, open-label, active-controlled, prospective, multinational phase III confirmative study the efficacy of intravesical instillations of abnobaVISCUM 900 and Mitomycin C (MMC) is compared. Patients with completely resected non muscle invasive bladder cancer stage Ta with an intermediate-risk classification according the European Association of Urology (EAU) guideline (update 2013) and with one immediately post-operative MMC 40 mg intravesical instillation will be included in this study. Eligible patients will be allocated to 2 treatment groups in a 1:1 ratio. The study period comprises 12 months of treatment and a follow up period of 12 months. All patients will receive 6 weekly intravesical instillations (induction therapy) and a maintenance therapy up to the end of the first year. The maintenance instillations will comprise one instillation every 6 weeks in the abnobaVISCUM arm and in the MMC arm one instillation with 40 mg every 12 weeks, in total 13 resp. 10 instillations up to the end of the first year. The follow up visits in the second year will take place every 12 weeks. Primary efficacy criterion is time to tumour recurrence, the secondary objective is to evaluate the safety of abnobaVISCUM 900 compared to MMC monotherapy. Statistically a two-stage procedure according to Bauer and Köhne will be performed. Results: The current sample size calculation for Stage I and II is 546 patients for both arms. Currently 31 centers in Germany and 1 in Egypt are contracted. This is thought to be adequate for the planned recruitment. Regulatory requirements including the necessary ethical votes are fulfilled, the study received a recommendation of the AUO (AB 40/11, Arbeitsgemeinschaft Urologische Onkologie [Urological Oncology Study Group], part of the Deutsche Krebsgesellschaft e.V. [German Cancer Society]. Recruitment of patients has been started. Keywords: bladder cancer, mistletoe, intravesical instillation, Phase III Clinical Trial EudraCT No.: 2013-003446-16. ClinicalTrials.gov Identifier: NCT02106572 doi: 10.1016/j.phymed.2015.05.062 Palliative mistletoe therapy in pancreatic cancer patients undergoing first-line chemotherapy (PALM-PAN)
Marcus Reif ∗, Alexandra Lemche Society for Clinical Research, Berlin, Germany ∗
Corresponding author. Tel.: +49 30 31574431. E-mail address: [email protected]
Purpose: Pancreatic cancer (PaCa) is a fatal disease with an extremely poor prognosis. Most PaCa patients die within the first year after diagnosis, and only 6% are alive after five years. Over the past decade PaCa death rates slowly increased, in contrast to the downward trend for most other major cancer sites. The lack of progress in primary prevention and early diagnosis as well as the merely modest effects of novel chemotherapy (CTx) regimens underscore the need