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

Dean Lim, Robert J. Morgan, Steven Akman, Kim Margolin, Brian I. Carr, Lucille Leong, Oluwole Odujinrin, James H. Doroshow

Research output: Contribution to journalArticlepeer-review


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/m 2 and escalating by modified Fibonacci scheme to 1360 mg/m 2. Toxicity was graded according to the Southwest Oncology Group toxicity scale with defined hypersensitivity reaction (HSR) scales. No grade ≥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/m 2, 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 μ M 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.

Original languageEnglish
Pages (from-to)235-239
Number of pages5
JournalInvestigational New Drugs
Issue number3
Publication statusPublished - Jun 2005


  • Menadiol
  • Menadione
  • Pharmacokinetics
  • Phase I
  • Solid tumor

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology


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