Purified Dry Paullinia cupana (PC-18) Extract for Chemotherapy-Induced Fatigue: Results of Two Double-Blind Randomized Clinical Trials

ABSTRACT

Fatigue is frequent among oncologic patients. Unpurified Paullinia cupana dry extract showed encouraging results for chemotherapy-induced fatigue in our previous studies. We report two randomized, double-blind studies with a standardized dry purified Paullinia cupana extract named PC-18. For both studies, we recruited early breast cancer patients who had an increase in their fatigue scores after their first cycle of adjuvant chemotherapy. In the first study, we compared an oral dose of 37.5 mg of PC-18 twice daily with placebo. In the second study, we examined PC-18 at either 7.5 or 12.5 mg orally twice daily versus placebo. In both studies, PC-18 was not superior to placebo as assessed by both Chalder and Brief Fatigue Inventory (BFI) fatigue questionnaires, probably reflecting unexpectedly good placebo antifatigue activity. Since all capsules employed in both studies contained about 100 mg of magnesium silicate as an excipient, we retrospectively evaluated frozen serum samples from the second study and found a significant increase in magnesium levels after patients received placebo. By multivariate analysis, higher prerandomization magnesium levels and higher BFI scores together with the use of a 12.5 mg dose of PC-18 all correlated significantly with higher posttreatment BFI scores. We observed no significant toxicities in any of the trials. We conclude that the absence of differences between PC-18 and placebo may be due to the unexpectedly high antifatigue activity of the placebo in these studies. Further studies evaluating the role of magnesium supplementation for chemotherapy-induced fatigue are needed.

KEYWORDS:

• Paullinia cupana
• chemotherapy-induced fatigue
• randomized control trial
• breast cancer

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Declaration of interest

The authors declare no conflicts of interest. The authors alone are responsible for the content and writing of the article.

About the authors

Claudia Vaz de Melo Sette, MD, is an Oncologist, ABC Medical School, Santo Andre, Brazil.

Bárbara Bonaparte Ribas de Alcântara, MD, is an Oncologist, ABC Medical School, Santo Andre, Brazil.

Jean Henri Maselli Schoueri is a Medical Student, ABC Medical School, Santo Andre, Brazil.

Felipe Melo Cruz, PhD, is an Assistant Professor of Medical Oncology, ABC Medical School, Santo Andre, Brazil.

Daniel de Iracema Gomes Cubero, PhD, is an Assistant Professor of Medical Oncology, ABC Medical School, Santo Andre, Brazil.

Luiz Francisco Pianowski, PhD, is a Pharmacist, Kyolab, Campinas, Sao Paulo, Brazil.

Luke Joseph Peppone, PhD, is a Research Assistant Professor in the University of Rochester, Rochester, NY, USA.

Fernando Fonseca, PhD, is the Chief of Clinical Laboratory of ABC Foundation School of Medicine, Santo Andre, Brazil.

Auro del Giglio, PhD, is the Chairman of Hematology and Oncology, ABC Medical School, Santo Andre, Brazil.