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Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy.

Publication ,  Journal Article
Lim, D; Morgan, RJ; Akman, S; Margolin, K; Carr, BI; Leong, L; Odujinrin, O; Doroshow, JH
Published in: Invest New Drugs
June 2005

Based on the activity of menadione (M) in the human tumor stem cell assay, we conducted a phase I trial of M in patients with advanced cancer. Forty patients (19 men, 21 women) were treated with 90 courses of M; 82 treatment courses are evaluable for toxicity. The median patient age, Karnofsky performance status, and number of prior chemotherapy regimens were 61 years (range 32-74 years), 80% (range 50-100%), and two, respectively. M was given by a short (1-5 h) intravenous infusion every 3 weeks, starting at 40 mg/m2 and escalating by modified Fibonacci scheme to 1360 mg/m2. Toxicity was graded according to the Southwest Oncology Group toxicity scale with defined hypersensitivity reaction (HSR) scales. No grade > or =2 hematologic toxicity was observed. Non-hematologic toxicity consisted of a HSR syndrome of paresthesiae of the extremities, facial flushing, burning of the eyes and mucous membranes, chest pain and dyspnea. HSR was defined as Grade I toxicity by the presence of facial numbness, flushing, and/or a tingling sensation or burning of the eyes and mucous membranes. Grade II toxicity was defined as the presence of the same above symptoms plus chest tightness, paresthesiae of extremities and/or dyspnea and chest pain. These toxicities were grade 1 in 3 of 4 patients at a dose of 840 mg/m2. At 1360 mg/m2, 2 of 13 patients suffered grade 1 HSR and 7 of 13 grade 2 HSR. No objective partial or complete responses were observed. Plasma menadione concentrations peaked at 1.9-7.4 microM during the infusion in 3 patients receiving 1360 mg/m2. Further phase 1 and 2 combination trials using longer infusion durations have resulted from this trial.

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Published In

Invest New Drugs

DOI

ISSN

0167-6997

Publication Date

June 2005

Volume

23

Issue

3

Start / End Page

235 / 239

Location

United States

Related Subject Headings

  • Vitamin K
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Karnofsky Performance Status
  • Infusions, Intravenous
  • Humans
  • Female
  • Dose-Response Relationship, Drug
 

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Lim, D., Morgan, R. J., Akman, S., Margolin, K., Carr, B. I., Leong, L., … Doroshow, J. H. (2005). Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy. Invest New Drugs, 23(3), 235–239. https://doi.org/10.1007/s10637-005-6731-2
Lim, Dean, Robert J. Morgan, Steven Akman, Kim Margolin, Brian I. Carr, Lucille Leong, Oluwole Odujinrin, and James H. Doroshow. “Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy.Invest New Drugs 23, no. 3 (June 2005): 235–39. https://doi.org/10.1007/s10637-005-6731-2.
Lim D, Morgan RJ, Akman S, Margolin K, Carr BI, Leong L, et al. Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy. Invest New Drugs. 2005 Jun;23(3):235–9.
Lim, Dean, et al. “Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy.Invest New Drugs, vol. 23, no. 3, June 2005, pp. 235–39. Pubmed, doi:10.1007/s10637-005-6731-2.
Lim D, Morgan RJ, Akman S, Margolin K, Carr BI, Leong L, Odujinrin O, Doroshow JH. Phase I trial of menadiol diphosphate (vitamin K3) in advanced malignancy. Invest New Drugs. 2005 Jun;23(3):235–239.
Journal cover image

Published In

Invest New Drugs

DOI

ISSN

0167-6997

Publication Date

June 2005

Volume

23

Issue

3

Start / End Page

235 / 239

Location

United States

Related Subject Headings

  • Vitamin K
  • Oncology & Carcinogenesis
  • Neoplasms
  • Middle Aged
  • Male
  • Karnofsky Performance Status
  • Infusions, Intravenous
  • Humans
  • Female
  • Dose-Response Relationship, Drug