title: A phase 1, open-label, dose-escalation study of pralatrexate in combination with bortezomib in patients with relapsed/refractory multiple myeloma.
abstract: Pralatrexate inhibits folic acid metabolism, and preclinical studies have shown that it is cytotoxic to multiple myeloma cells. This phase 1 study investigated the safety and efficacy of pralatrexate in combination with bortezomib in adults with relapsed or refractory multiple myeloma. A standard 3 + 3 design was used. Patients received intravenous pralatrexate at doses ranging from 10 to 30 mg/m(2) and intravenous bortezomib at a dose of 1·3 mg/m(2) on days 1, 8 and 15 of each 4-week cycle. Eleven patients were enrolled and completed a median of two cycles. The maximum tolerated dose was 20 mg/m(2) . Two patients experienced dose-limiting toxicity of mucositis. The most frequent non-haematological toxicities were fatigue (55%) and mucositis (45%). There were three serious adverse events in three patients: rash, sepsis and hypotension. One patient (9%) had a very good partial response, 1 (9%) had a partial response, 1 (9%) had minimal response and two (18%) had progressive disease. The median duration of response was 4 months, the median time to next treatment was 3·4 months and the median time to progression was 4 months. Pralatrexate, in combination with bortezomib, was generally safe and demonstrated modest activity in relapsed or refractory multiple myeloma. Clinicaltrials.gov identifier: NCT01114282.
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Tamara J
authors.initials: TJ
authors.lastname: Dunn
authors.affiliation: Division of Hematology/Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors.forename: Shira
authors.initials: S
authors.lastname: Dinner
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Price
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Steven E
authors.initials: SE
authors.lastname: Coutré
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Gotlib
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hao
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Caroline
authors.initials: C
authors.lastname: Berube
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Bruno C
authors.initials: BC
authors.lastname: Medeiros
authors.affiliation: Division of Hematology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Michaela
authors.initials: M
authors.lastname: Liedtke
mesh_terms: D000368:Aged; D000630:Aminopterin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: C418863:10-propargyl-10-deazaaminopterin; D000069286:Bortezomib; D000630:Aminopterin
keywords: bortezomib; multiple myeloma; pralatrexate; refractory; relapsed