PURPOSE: To determine the maximum-tolerated dose (MTD) and efficacy of pralatrexate in patients with lymphoma. PATIENTS AND METHODS: Pralatrexate, initially given at a dose of 135 mg/m(2) on an every-other-week basis, was associated with stomatitis. A redesigned, weekly phase I/II study established an MTD of 30 mg/m(2) weekly for six weeks every 7 weeks. Patients were required to have relapsed/refractory disease, an absolute neutrophil greater than 1,000/microL, and a platelet count greater than 50,000/microL for the first dose of any cycle. RESULTS: The every-other-week, phase II experience was associated with an increased risk of stomatitis and hematologic toxicity. On a weekly schedule, the MTD was 30 mg/m(2) weekly for 6 weeks every 7 weeks. This schedule modification resulted in a 50% reduction in the major hematologic toxicities and abrogation of the grades 3 to 4 stomatitis. Stomatitis was associated with elevated homocysteine and methylmalonic acid, which were reduced by folate and vitamin B12 supplementation. Of 48 assessable patients, the overall response rate was 31% (26% by intention to treat), including 17% who experienced complete remission (CR). When analyzed by lineage, the overall response rates were 10% and 54% in patients with B- and T-cell lymphomas, respectively. All eight patients who experienced CR had T-cell lymphoma, and four of the six patients with a partial remission were positron emission tomography negative. The duration of responses ranged from 3 to 26 months. CONCLUSION: Pralatrexate has significant single-agent activity in patients with relapsed/refractory T-cell lymphoma.
PURPOSE: To determine the maximum-tolerated dose (MTD) and efficacy of pralatrexate in patients with lymphoma. PATIENTS AND METHODS: Pralatrexate, initially given at a dose of 135 mg/m(2) on an every-other-week basis, was associated with stomatitis. A redesigned, weekly phase I/II study established an MTD of 30 mg/m(2) weekly for six weeks every 7 weeks. Patients were required to have relapsed/refractory disease, an absolute neutrophil greater than 1,000/microL, and a platelet count greater than 50,000/microL for the first dose of any cycle. RESULTS: The every-other-week, phase II experience was associated with an increased risk of stomatitis and hematologic toxicity. On a weekly schedule, the MTD was 30 mg/m(2) weekly for 6 weeks every 7 weeks. This schedule modification resulted in a 50% reduction in the major hematologic toxicities and abrogation of the grades 3 to 4 stomatitis. Stomatitis was associated with elevated homocysteine and methylmalonic acid, which were reduced by folate and vitamin B12 supplementation. Of 48 assessable patients, the overall response rate was 31% (26% by intention to treat), including 17% who experienced complete remission (CR). When analyzed by lineage, the overall response rates were 10% and 54% in patients with B- and T-cell lymphomas, respectively. All eight patients who experienced CR had T-cell lymphoma, and four of the six patients with a partial remission were positron emission tomography negative. The duration of responses ranged from 3 to 26 months. CONCLUSION:Pralatrexate has significant single-agent activity in patients with relapsed/refractory T-cell lymphoma.
Authors: B D Cheson; S J Horning; B Coiffier; M A Shipp; R I Fisher; J M Connors; T A Lister; J Vose; A Grillo-López; A Hagenbeek; F Cabanillas; D Klippensten; W Hiddemann; R Castellino; N L Harris; J O Armitage; W Carter; R Hoppe; G P Canellos Journal: J Clin Oncol Date: 1999-04 Impact factor: 44.544
Authors: L M Krug; K K Ng; M G Kris; V A Miller; W Tong; R T Heelan; L Leon; D Leung; J Kelly; S C Grant; F M Sirotnak Journal: Clin Cancer Res Date: 2000-09 Impact factor: 12.531
Authors: Lee M Krug; Christopher G Azzoli; Mark G Kris; Vincent A Miller; Nushmia Z Khokhar; William Tong; Michelle S Ginsberg; Ennapadam Venkatraman; Leslie Tyson; Barbara Pizzo; Valerie Baez; Kenneth K Ng; F M Sirotnak Journal: Clin Cancer Res Date: 2003-06 Impact factor: 12.531
Authors: D R Mould; K Sweeney; S B Duffull; E Neylon; P Hamlin; S Horwitz; F Sirotnak; M Fleisher; M E Saunders; O A O'Connor Journal: Clin Pharmacol Ther Date: 2009-05-27 Impact factor: 6.875
Authors: Kieron Dunleavy; Richard L Piekarz; Jasmine Zain; John E Janik; Wyndham H Wilson; Owen A O'Connor; Susan E Bates Journal: Clin Cancer Res Date: 2010-12-01 Impact factor: 12.531