title: A phase I human trial of mitoguazone and gemcitabine sequential bi-weekly treatment of cancer patients.
abstract: Our previous studies have demonstrated the existence of synergism in a combination therapy using mitoguazone and gemcitabine when the mitoguazone is administered 24 hours before gemcitabine. Based on the cell culture and animal experimental results, a phase I clinical trial was performed in order to determine the toxicity of the combined treatment. Mitoguazone and gemcitabine were administered sequentially: mitoguazone on day 1 and gemcitabine on day 2. This cycle was repeated every 2 weeks. The dosages of these two drugs were varied between patients. Ten patients were enrolled in the study. Six patients began treatment at dose level 1 (mitoguazone 500 mg/m2, gemcitabine 1500 mg/m2), three at dose level 2 (mitoguazone 500 mg/m2, gemcitabine 2000 mg/m2), and one at dose level 3 (mitoguazone 600 mg/m2, gemcitabine 2000 mg/m2). Dose-limiting toxicity (DLT) was only observed in two patients treated at dose level 1 and one patient treated at dose level 3, while all the other patients only experienced nonhematologic toxicity, such as asthenia and mucositis. Two melanoma patients showed responses (one partial and one minor) to the treatment. One lymphoma patient also showed a brief partial response. This phase I trial indicated that the combination of mitoguazone and gemcitabine had limited but noticeable activity for treatment of cancer patients. Further study on the toxicity and on the effect of the scheduled mitoguazone-gemcitabine combination is needed.
authors.affiliation: Cancer Treatment Center of Oklahoma, 3945 North Walnut Street, Oklahoma City, Oklahoma 73015, USA. ishdr@aol.com
authors.forename: D Richard
authors.initials: DR
authors.lastname: Ishmael
authors.forename: Wei R
authors.initials: WR
authors.lastname: Chen
authors.forename: Steven A
authors.initials: SA
authors.lastname: Hamilton
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
authors.forename: Robert E
authors.initials: RE
authors.lastname: Nordquist
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D008935:Mitoguazone / Q000008:administration & dosage; D009369:Neoplasms / Q000188:drug therapy*; D000093542:Gemcitabine
chemical_list: D003841:Deoxycytidine; D008935:Mitoguazone; D000093542:Gemcitabine