Troger, W., Galun, D., Reif, M., Schumann, A., Stankovic, N., & Milicevic, M. (2014). Quality of life of patients with advanced pancreatic cancer during treatment with mistletoe: A randomized controlled trial. Deutsches Arzteblatt International, 111, 493–502, 33 p following 502. 

To evaluate the impact of mistletoe extract injections on overall survival and quality of life in patients with advanced pancreatic cancer

Escalating doses of mistletoe extract were self-administered by patients as a 1 ml subcutaneous injection three times a week for the duration of the trial (up to one year) by the patient, a family member, or the local treatment center staff. The dose was escalated as follows: 0.01 mg for two injections, 0.1 mg for two injections, 1 mg for five injections, 2 mg for five injections, 5 mg for eight injections, and 10 mg for the remainder of the injections. Patients were evaluated by completing the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-C30) at seven timepoints (at enrollment and before each visit in months 1, 2, 3, 6, 9, and 12). Patients were evaluated by the physician at each visit for the severity of symptoms of cancer (including weight loss) and undesired events.

• N = 168  
• AGE = 98 patients were aged 18–65 years, and 70 patients were aged greater than 65 years.
• MALES: 56%, FEMALES: 44%
• KEY DISEASE CHARACTERISTICS: Locally advanced or metastatic pancreatic cancer
• OTHER KEY SAMPLE CHARACTERISTICS: Not receiving any treatment other than best supportive care

• SITE: Multi-site  
• SETTING TYPE: Multiple settings    
• LOCATION: Serbia

• PHASE OF CARE: Active antitumor treatment
• APPLICATIONS: Palliative care

Prospective, randomized trial (randomized 1:1 ratio to mistletoe injections or control after stratification for prognosis of good or poor)

• EORTC-QLQ-C30 (five functional scales, nine symptom scales, and one global quality of health scale)
• Common Terminology Criteria for Adverse Events (CTCAE)

All questionnaires were evaluated at the end of the trial. The treatment group received a median of 61.5 mistletoe injections. The treatment improved the global quality of life with statistical significance (p < 0.001) for global quality of life, appetite loss, fatigue, pain, and nausea at various follow-up time periods. The number of questionnaires received at various time points in the study ranged from 0–110 in the control group and 19–110 in the mistletoe group. The number of documented injections ranged from 3–156 per patient. No side effects were reported. The trial was terminated early because of demonstrated efficacy.

The results of the patient-completed quality of life questionnaires were reported with improvements in 13 of the 15 scales in the group treated with mistletoe. The administration of mistletoe was associated with improvements in appetite loss, fatigue, and pain.

• Risk of bias (no blinding)
• Selective outcomes reporting
• Measurement/methods not well described
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: Patient self-reporting bias; tool scoring not described; limited to one cancer diagnosis; injections were to be self-administered by the patients and there is no information provided on degree of patient adherence to the study regimen; range of injections reported suggests that a number of patients did not receive all of the expected injections; no placebo comparison; large amount of missing data; approach regarding intent to treat analysis is unclear as the statistical methods are described

The findings of this study suggest that mistletoe may be beneficial to patients with advanced cancer for multiple symptoms. The positive findings of this study suggest that additional research in this area is warranted.