NCCAM/NCI phase 1 study of mistletoe extract and Gemcitabine in patients with advanced solid tumors.
Background: European mistletoe extracts are used for cancer treatment in Europe. Controlled studies of safety and toxicity in cancer treatment based on dosing have not been published. This novel phase 1 dose escalation study of mistletoe with Gemcitabine (GEM) assessed safety, toxicity and pharmakodynamics in patients with advanced solid cancers.
Methods: Forty-four patients with advanced solid tumors received 3 cycles of GEM and mistletoe with escalating doses of mistletoe (Helixor A) during stage 1 (1-20, 1-50, 1-100, 1-200, and 1-250 mg s.c. daily, respectively) and GEM during stage 2 (900-1680 mg/[m.sup.2]). GEM plasma concentrations (Cp) were determined during stage I. Plasma cytokine concentrations and anti-mistletoe lectin (ML)3 antibodies were measured.
Results: Dose limiting toxicities (DLT) included grade 4 neutropenia, grade 4 thrombocytopenia, grade 3 cellulitis and grade 4 acute renal failure. Gemcitabine 1300 mg/[m.sup.2] (a 30% higher dose than recommended in GEM single agent treatment) and mistletoe 250 mg were the Maximum Tolerated Dose (MTD). 24/44 developed non-neutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed anti-ML3 IgG antibodies. Plasma cytokine concentrations were minimally affected. ANC (absolute neutrophil count) values showed a trend to increase between baseline and C2 in stage I. Partial response and stable disease were found in 6% and 42% of patients, respectively, all in patients with pancreatic cancer with median Progression-free Surnival (PFS) of 78 days. Median overall survival was 190 days. Compliance with mistletoe injections varied from 78.6 to 100%.
Conclusions: The mistletoe/GEM combination demonstrated limited toxicity, no alterations of GEM Cp (plasma concentration), clinical benefit in 48% of patients, especially in pancreatic cancer, good tolerability and excellent mistletoe compliance. Addition of mistletoe may allow for use of higher doses of GEM and increase the ANC nadir. No effects on the measured cytokines were observed.
Keywords: Mistletoe; Safety and toxicity; Phase I trial
P.J. Mansky (a), (b), *, D.B. Wallersteclt (b), T. Sannes (b), J. Stagl (b), L.L. Johnson (b), M.R.BIackman (c), J.L. Grem (d), S.M. Swain (e), D.Schlodder (f), B.P. Monahan(g)
(a) Bellin Health, Green Bay, WI, United States
(b) National Center for Complementary and Alternative Medicine, NIH, Bethesda, MD, United States
(c) Research Service, Veterans Affairs Medical Center, Washington, D.C., United States
(d) Univ Nebraska Medcl Ctr, Omaha, NE, United States
(e) Washington Hosp Ctr, Washington, DC, United States
(f) Helixor Heilmittel GmbH & Co, KG, Rosenfeid, Germany
(g) The Attending Physician, Congress of the United States, Washington, DC, United States
* Corresponding author. Tel.: +1 920 544 6452. E-mail address: email@example.com (P.J. Mansky).
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|Author:||Mansky, P.J.; Wallerstedt, D.B.; Sannes, T.; Stagl, J.; Johnson, L.L.; Blackman, M.R.; Grem, J.L.; S|
|Publication:||Phytomedicine: International Journal of Phytotherapy & Phytopharmacology|
|Date:||Oct 15, 2011|
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