title: A phase II multicenter study of troxacitabine in relapsed or refractory lymphoproliferative neoplasms or multiple myeloma.
abstract: Options for patients with relapsed/refractory lymphoproliferative disorders and multiple myeloma are currently limited. Troxacitabine has shown promise in preclinical studies in a variety of malignancies; hence, the current study was conducted to evaluate the activity of troxacitabine in relapsed or refractory lymphoid malignancies. This was a phase II, open-label, multinational, multicenter study of patients with relapsed or refractory lymphoproliferative disorders or multiple myeloma. Thirty-four adults were enrolled in the study and received the study drug at either 5.4 mg/m2 (n = 16) or 4.3 mg/m2 (n = 18). The dose was decided in a phase I study, during which dose escalation was carried to reach a maximum tolerated dose with an acceptable toxicity profile. Two separate phase I studies were performed in Europe and the US. Troxacitabine was administered by intravenous infusion over 30 min daily for days 1 - 5 every 4 weeks. Treatment was continued to disease progression or until the subjects met criteria for withdrawal or unacceptable toxicities were evident as outlined in the protocol. Two patients had a partial response (PR) to treatment with troxacitabine to yield an overall response rate of 13%. There were no complete responses seen with the drug. Stable disease was achieved in 15 patients (44%). All patients had at least one treatment related adverse event, which led to six withdrawals from the study. Hematologic toxicity constituted the most common adverse events. Serious adverse effects were seen in 62% of patients. None of the 13 deaths were attributed directly to troxacitabine. As a single agent, troxacitabine has limited benefit in patients with advanced lymphoproliferative disorders or multiple myeloma. Future studies will be needed to address modified dosing according to emerging pharmacokinetic and pharmacodynamic data and combination therapy which may lead to improved clinical benefit for troxacitabine in hematologic malignancies.
authors.affiliation: University of Nebraska Medical Center, Omaha, NE 68198-7680, USA. jmvose@unmc.edu
authors.forename: Julie M
authors.initials: JM
authors.lastname: Vose
authors.forename: Amit
authors.initials: A
authors.lastname: Panwalkar
authors.forename: Robert
authors.initials: R
authors.lastname: Belanger
authors.forename: Bertrand
authors.initials: B
authors.lastname: Coiffier
authors.forename: Michele
authors.initials: M
authors.lastname: Baccarani
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Gregory
authors.forename: Thierry
authors.initials: T
authors.lastname: Facon
authors.forename: Renato
authors.initials: R
authors.lastname: Fanin
authors.forename: Dolores
authors.initials: D
authors.lastname: Caballero
authors.forename: Dina
authors.initials: D
authors.lastname: Ben-Yehuda
authors.forename: Francis
authors.initials: F
authors.lastname: Giles
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D003596:Cytosine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004148:Dioxolanes / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005260:Female; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000401:mortality; D008223:Lymphoma / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D012008:Recurrence; D016879:Salvage Therapy; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D004148:Dioxolanes; C074908:troxacitabine; D003596:Cytosine