Nccam/nci phase 1 study of mistletoe extract and gemcitabine in patients with advanced solid tumors

Patrick J. Mansky, Dawn B. Wallerstedt, Timothy S. Sannes, Jamie Stagl, Laura Lee Johnson, Marc R. Blackman, Jean L Grem, Sandra M. Swain, Brian P. Monahan

Research output: Contribution to journalArticle

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Abstract

Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

Original languageEnglish (US)
Article number964592
JournalEvidence-based Complementary and Alternative Medicine
Volume2013
DOIs
StatePublished - Dec 4 2013

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gemcitabine
Mistletoe
Neoplasms
Maximum Tolerated Dose
Viscum album
Neutrophils
Pharmacokinetics
Cellulitis
Survival
Antibodies

ASJC Scopus subject areas

  • Complementary and alternative medicine

Cite this

Mansky, P. J., Wallerstedt, D. B., Sannes, T. S., Stagl, J., Johnson, L. L., Blackman, M. R., ... Monahan, B. P. (2013). Nccam/nci phase 1 study of mistletoe extract and gemcitabine in patients with advanced solid tumors. Evidence-based Complementary and Alternative Medicine, 2013, [964592]. https://doi.org/10.1155/2013/964592

Nccam/nci phase 1 study of mistletoe extract and gemcitabine in patients with advanced solid tumors. / Mansky, Patrick J.; Wallerstedt, Dawn B.; Sannes, Timothy S.; Stagl, Jamie; Johnson, Laura Lee; Blackman, Marc R.; Grem, Jean L; Swain, Sandra M.; Monahan, Brian P.

In: Evidence-based Complementary and Alternative Medicine, Vol. 2013, 964592, 04.12.2013.

Research output: Contribution to journalArticle

Mansky, PJ, Wallerstedt, DB, Sannes, TS, Stagl, J, Johnson, LL, Blackman, MR, Grem, JL, Swain, SM & Monahan, BP 2013, 'Nccam/nci phase 1 study of mistletoe extract and gemcitabine in patients with advanced solid tumors', Evidence-based Complementary and Alternative Medicine, vol. 2013, 964592. https://doi.org/10.1155/2013/964592
Mansky, Patrick J. ; Wallerstedt, Dawn B. ; Sannes, Timothy S. ; Stagl, Jamie ; Johnson, Laura Lee ; Blackman, Marc R. ; Grem, Jean L ; Swain, Sandra M. ; Monahan, Brian P. / Nccam/nci phase 1 study of mistletoe extract and gemcitabine in patients with advanced solid tumors. In: Evidence-based Complementary and Alternative Medicine. 2013 ; Vol. 2013.
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abstract = "Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6{\%} of patients showed partial response, 42{\%} stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.",
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AU - Stagl, Jamie

AU - Johnson, Laura Lee

AU - Blackman, Marc R.

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AU - Swain, Sandra M.

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N2 - Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

AB - Purpose. European Mistletoe (Viscum album L.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM. Methods. Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery. Results. DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2 and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high. Conclusion. GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.

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