In Reply

Letters to the Editor regarding the article Mistletoe Extract in Patients With Advanced Pancreatic Cancer by Kathrin Wode, Gunver S. Kienle, Ove Björ, Per Fransson, Lena Sharp, Nils O. Elander, Britt-Marie Bernhardson, Birgit Johansson, Christina Edwinsdotter Ardnor, Ursula Scheibling, Johanna Hök Nordberg, and Roger Henriksson in issue 11/2024

The double-blind, placebo-controlled MISTRAL trial (1) on mistletoe extract (ME) aimed at providing transparent, reliable, and robust information to guide treatment decisions in patients with pancreatic cancer. The experience and results from the preceding Serbian MAPAC-trial (2,3) were taken into account when designing MISTRAL.

The MISTRAL population is closely comparable with the routine clinical situation: survival times similar to those in other publications, and best supportive care and chemotherapy compatible with the standard of care in most countries with modern healthcare systems. By contrast, the palliative treatment in MAPAC (pain medication in 68%, no chemotherapy despite ECOG 0–1 in 50% of participants) implies low external validity and raises ethical questions.

The suggested ceiling effect—an optimal state of health cannot be improved further by ME—is unlikely, given the short survival of the patients in the MISTRAL trial. An effect should have become apparent later, when the global health status/quality of life deteriorated. The pertinent literature gives no indication that ME is less efficient in patients who start with a better condition and survive longer, or if ME is added to anticancer treatment. Moreover, subgroup analyses did not indicate a potential interference by corticosteroids.

Given the open-label design in MAPAC, the ME group may have reported a better quality of life out of gratitude or courtesy. This may explain the unusually sharp initial rise and subsequent steady increase in quality of life until death in patients receiving ME. Whether unrelieved symptoms, pain, or nausea due to inadequate palliative treatment may have influenced the participants’ answers remains open to discussion. We believe that the MISTRAL results are highly valid—internally and externally.

DOI: 10.3238/arztebl.m2024.0190

On behalf of the authors

Dr. Kathrin Wode, PhD, MD

Regional Cancer Centre Stockholm Gotland, Sweden

Conflict of interest statement

The author declares that no conflict of interest exists.

References

1. Wode K, Kienle GS, Bjor O, et al.: Mistletoe extract in patients with advanced pancreatic cancer: a double-blind, randomized, placebo-controlled trial (MISTRAL). Dtsch Arztebl Int 2024; 121; 347–54.

2. Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M: Viscum album [L.] extract therapy in patients with locally advanced or metastatic pancreatic cancer: a randomised clinical trial on overall survival. Eur J Cancer 2013; 49: 3788–97.

3. Tröger W, Galun D, Reif M, Schumann A, Stankovic N, Milicevic M: Quality of life of patients with advanded pancreatic cancer during treatment with mistletoe. A randomized controlled trial. Dtsch Arztebl Int 2014; 111: 493–502.