By Chris Berrie
LUGANO, SWITZERLAND -- July 9, 2007 -- Use of a fermented mistletoe extract (MEx; Iscador®) in long-term supportive care in hospitals and private practices demonstrated significant survival benefit and improvements in quality of life for patients with surgically treated primary, nonmetastatic colorectal carcinoma and for patients with all-stages pancreatic carcinoma, when combined with adjuvant chemotherapy and/or radiotherapy or passive aftercare in two multicentre, controlled, retrospective, epidemiological, observational, cohort studies.
These findings were presented here on July 7th at the European Society for Medical Oncology (ESMO) Conference.
The primary nonmetastatic colorectal carcinoma study was presented by principal investigator Walter Eckart Friedel, MD, PhD, Director, Bad Bocklet Clinic, and Head, Department of Internal Medicine and Oncology, Hospital Bad Bocklet, Bad Bocklet, Germany.
The parallel study on all-stages pancreatic carcinoma (pancreatic study) was presented by Friedemann Schad, MD, PhD, Director, Research Institute Havelhöhe (FIH), and Consultant, Department of Gastroenterology, Hospital Havelhöhe, Berlin, Germany.
As Dr. Schad said, "Mistletoe extract has been used for tens of years in Germany and Switzerland, and it is always said to have a positive effect on life quality, a positive effect in the reduction of side effects of conventional therapy, and also a positive effect on hard outcomes like overall survival. But there is still a lack of clinical research."
In both studies, the fermented extract from Viscum album L. (MEx) was administered subcutaneously 2 to 3 times per week as part of long-term supportive care in hospitals and private practices.
According to Dr. Schad, "The aim was to see what effect mistletoe has, as this Iscador® preparation, in addition to conventional therapy, in terms of life quality and outcome."
Both trials used unselected anonymous data from medical records that satisfied eligibility criteria. These data were documented chronologically in standardised case-report forms. The follow-up lasted until the last visit or death of the patient.
The outcome endpoints were tumour-free survival in the colorectal study and overall survival in the pancreatic study. In addition, both studies evaluated patients quality of life according to the following surrogate criteria: adverse drug reaction (ADR) rates attributed to the conventional adjuvant chemotherapy and/or radiotherapy; persistence of disease- and treatment-associated symptoms; mean functional capacity (Karnofsky index); and mean duration of hospitalisation during therapy and follow-up.
All endpoint data were adjusted for confounder effects by multivariate analyses. The predefined confounders included: age; gender; centre group; non-oncological chronic diseases; chemotherapy; radiotherapy; duration of chemotherapy; additional supportive therapy with high-dose vitamins, minerals and trace elements; tumour-specific conditions.
The colorectal study included 804 patients, 429 with MEx use (mean age, 57.2 years; male, 51.1%), and 375 controls (mean age, 62.8 years; male, 53.3%); for the pancreatic group, the numbers were 396, as 201 with MEx use (mean age, 58.2 years; male, 55.7%) and 195 controls (mean age, 63.7 years; male, 49.7%). These patients were either treated surgically for primary nonmetastatic colorectal carcinoma or treated for pancreatic carcinoma, respectively, and they all received oncological treatment and supportive care.
For ADRs to adjuvant chemotherapy and/or radiotherapy, in the colorectal group significantly fewer of the MEx patients experienced adjuvant-therapy-induced ADRs: 19.1% versus 48.3% (P <.001). The equivalent in the pancreatic group showed 13.7% versus 48.9% (P <.001).
Over the range of disease- and therapy-related symptoms analysed for estimated risk of each symptom persistence or new occurrence, both carcinoma groups showed significant benefit for the MEx patients over the control patients.
As Dr. Friedel indicated for the colorectal group, "Especially gastrointestinal symptoms, like nausea, vomiting, diarrhoea, were significantly lower, and the central nervous system [symptoms] were better, like depression, disturbed memory and disturbed sleep."
Functional capacity improved significantly in both the colorectal and pancreatic cancer groups (P <.001). Similarly, there was significantly decreased duration of hospitalisation with the MEx versus control patients: 35.5 versus 41.2 days in the colorectal cancer study (P =.015) and 30.3 versus 46.9 days in the pancreatic cancer study (P <.001).
Tumour-free survival in the colorectal group was expressed as the relative hazard of expecting a first tumour-related event, with the hazard ratio showing benefit for MEx use as 0.68 (95% confidence interval [CI], 0.51-0.92; P =.013). Similarly, the OS for MEx use in the pancreatic group saw a beneficial hazard ratio of 0.58 (95% CI, 0.42-0.79; P =.001).
As expected, the ADRs relating to MEx use were low: 2.3% in the colorectal study and 1.5% in the pancreatic study. Also, local ADRs at the injection site were also similar (23.3% and 22.4%), and no tumour enhancement was seen for MEx use; hence it was well tolerated and can be considered safe, according to the researchers.
Dr. Schad said, "Although it is a retrospective cohort study, we see in each endpoint a benefit for the mistletoe group."
In both of these carcinoma groups, addition of MEx use to supportive care with adjuvant chemotherapy shows significant benefits across a range of disease and quality of life measures. "The next step has to be a prospective controlled trial," he concluded.
Funding for this research was provided by Weleda AG, Switzerland.
[Presentation title: Mistletoe in Supportive Care in Patients With Primary Non-Metastatic Colorectal Carcinoma. Abstract 45P. Supportive Care in Pancreatic Carcinoma Patients Treated With a Fermented Mistletoe (Viscum Album L.) Extract. Abstract 136P]
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