Mistletoe Extract

The purpose of this article was to determine the clinical response identified as quality of life, including fatigue and neutropenia, in patients receiving CAF for breast cancer with additional treatment with mistletoe extract compared to chemotherapy alone.

Ninety-five patients were randomized into three groups. All patients received chemotherapy with six cycles of chemotherapy with cyclophosphamide, adriamycin, and 5-flourouracil (CAF). Two groups also received Iscador administered by subcutaneous injection, containing 1 ml of varying amounts of fermented extract of fresh mistletoe herb or a different mistletoe preparation. IMS was incrementally increased from 0.01–5 mg of the herb in isotonic saline. The control group (n = 31) was compared to group who received IMS (n = 30). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QOQ-C30) was used to assess quality of life, including fatigue. An absolute neutrophil count of less than 1,000 mcl defined neutropenia and was assessed at baseline and one day prior to each cycle of CAF chemotherapy.

• The total sample size was 60 with all participants aged 18 or older.
• All participants were female
• All had early-stage breast cancer (stages T_1-3N_0-2M₀)
• Participants had to be female, 18 years or older, have a Karnofsky-Index of 60 or greater, leucocytes of 3,000/mm³ or higher, thrombocytes of 100,000/mm³ or higher, serum creatinine of 2 mg or less, serum glutamic oxaloacetic transaminase (SGOT), and serum glutamic pyruvic transaminase (SGPT) less than or equal to 2.5 times the upper institutional limits
• Women were excluded if they were pregnant or lactating, had metastatic disease, planned to receive hormone or radiation therapy during six cycles of CAF, used immunostimulant or immunosuppressive agents (e.g., corticosteroids) except for nausea and vomiting, were currently taking other investigational agents, had clinically relevant physical or mental illness including serious infections, hepatic, renal or other organ dysfunction, had major depression, suffered from alcohol abuse or alcoholism, suffered from drug abuse either oral or parental, and were in methadone treatment.
   

A single-site oncology and radiology institute in Belgrade, Serbia

• The phase of care was during active treatment with chemotherapy
• Application was for  prevention of infection; quality of life with neutropenia
   

Prospective, randomized, open-label pilot

• EORTC-QLQ-C30
• Neutropenia assessment was reported by measuring the number of patients with less than 1,000 mcl neutrophils throughout the study.    
   

Quality of life decreased from baseline in all scores of control group participants and in six scores in the IMS group. The most significant decreases in scores were seen for nausea/emesis (17.2 score points) and fatigue (8.2 score points) following the second cycle of CAF chemotherapy. Decreases in insomnia (13.1 score points) and diarrhea (11.9 score points) were reported after the third cycle of CAF chemotherapy.

An adjusted analyses that compared mean differences from baseline of the control and IMS groups revealed that all 15 comparisons favored the IMS group, 12 comparisons showed significant differences (p = 0.017–0.001). The IMS group were favored over the control group, with a clinically relevant differences of 5 points or more for nine of the EORTC-QLQ-C30 scores. Statistically significant improvement in symptoms with IMS compared to controls were found for physical functioning, role functioning, emotional functioning, social functioning, fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, diarrhea, and financial difficulties

Neutropenia was identified three times in three different patients within the IMS group and nine times in eight different patients of the control group. Odds ratio for the proportion of patients with neutropenia in IMS group versus control group was 0.32 (95% CI [0.08, 1.35]).  

Localized skin reactions to IMS occurred in six patients. No other adverse events were reported, and findings with use of the other mistletoe preparation are not reported.
 

For patients receiving CAF chemotherapy for early stage-breast cancer, adding mistletoe therapy improved quality of life and demonstrated a trend toward reduction of neutropenia.

• Sample size was small
• Trial was not blinded or placebo controlled.  It is not clear if there was an effect simply because patients were receiving an injection. 
• No information on the other mistletoe preparation is provided. 
• Effects on neutropenia cannot be really evaluated due to limited information reported. 
• There was only a 120 day follow-up period.
   

Findings suggest that mistletoe might have some applicability in managing symptoms for patients with cancer, and may have an effect on neutropenia. Findings of this study are severely effected by limitations in study design and the small sample size that makes meaningful analysis of some outcomes of interest difficult. As a result, this study does not provide strong support for efficacy of mistletoe use.