TY - JOUR
T1 - Identification of an active, well-tolerated dose of pralatrexate in patients with relapsed or refractory cutaneous T-cell lymphoma
AU - Horwitz, Steven M.
AU - Kim, Youn H.
AU - Foss, Francine
AU - Zain, Jasmine M.
AU - Myskowski, Patricia L.
AU - Lechowicz, Mary Jo
AU - Fisher, David C.
AU - Shustov, Andrei R.
AU - Nancy, L. Bartlett
AU - Maria, L. Delioukina
AU - Tony Koutsoukos, Koutsoukos
AU - Michael, E. Saunders
AU - Owen, A. O.Connor
AU - Madeleine Duvic, Duvic
N1 - Funding Information:
The authors appreciate the funding from Universiti Sains Malaysia Research University Grant (1001/PPSP/811082). The authors would also like to thanks Ms. Azilla from the School of Health Sciences for her technical assistance in the research.
PY - 2012/5/3
Y1 - 2012/5/3
N2 - Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1.Adose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma, with disease progression after > 1 prior systemic therapy. The starting dose and schedule was 30 mg/m2/wk intravenously for 3 of 4 (3/4) weeks. Subsequent starting doses were 20, 15, and 10 mg/m2/wk for 3/4 or 2 of 3 (2/3) weeks. Response was evaluated by the modified severity-weighted adjustment tool. Fiftyfour patients were treated. The recommended regimen was identified as 15 mg/ m2/wk for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated overall with the recommended dosing regimen, the median number of prior systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles; response rate was 45%. The most common grade 3 adverse event (AE) was mucositis (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m2/wk for 3/4 weeks shows high activity with acceptable toxicity in patients with relapsed/refractory CTCL.
AB - Systemic treatment for cutaneous T-cell lymphoma (CTCL) involves the use of less aggressive, well-tolerated therapies. Pralatrexate is a novel antifolate with high affinity for reduced folate carrier-1.Adose de-escalation strategy identified recommended pralatrexate dosing for patients with CTCL that demonstrated high activity, good rates of disease control, and an acceptable toxicity profile for continuous long-term dosing. Eligibility included mycosis fungoides, Sézary syndrome, or primary cutaneous anaplastic large cell lymphoma, with disease progression after > 1 prior systemic therapy. The starting dose and schedule was 30 mg/m2/wk intravenously for 3 of 4 (3/4) weeks. Subsequent starting doses were 20, 15, and 10 mg/m2/wk for 3/4 or 2 of 3 (2/3) weeks. Response was evaluated by the modified severity-weighted adjustment tool. Fiftyfour patients were treated. The recommended regimen was identified as 15 mg/ m2/wk for 3/4 weeks and was explored in the expansion cohort. In 29 patients treated overall with the recommended dosing regimen, the median number of prior systemic therapies was 4. Pralatrexate was administered for a median of 4 cycles; response rate was 45%. The most common grade 3 adverse event (AE) was mucositis (17%); the only grade 4 AE was leukopenia (3%). Pralatrexate 15 mg/m2/wk for 3/4 weeks shows high activity with acceptable toxicity in patients with relapsed/refractory CTCL.
UR - http://www.scopus.com/inward/record.url?scp=84860775360&partnerID=8YFLogxK
U2 - 10.1182/blood-2011-11-390211
DO - 10.1182/blood-2011-11-390211
M3 - Article
C2 - 22394596
AN - SCOPUS:84860775360
SN - 0006-4971
VL - 119
SP - 4115
EP - 4122
JO - Blood
JF - Blood
IS - 18
ER -