Results from a Phase I/II Open-Label, Dose-Finding Study of Pralatrexate and Oral Bexarotene in Patients with Relapsed/Refractory Cutaneous T-cell Lymphoma.
Purpose:Pralatrexate is a folic acid analogue metabolic inhibitor similar to methotrexate, which has shown tolerability and efficacy with an overall response rate of 45% in a phase I dose deescalation study of patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL).Experimental Design:The object of this phase I/II open-label, multicenter clinical trial was to determine the MTD and recommended dose of pralatrexate plus oral bexarotene in 34 patients with relapsed/refractory CTCL who had failed prior systemic therapies. Pralatrexate was administered by intravenous push at 15 mg/m2given weekly 3 weeks out of 4 weeks with daily oral bexarotene (150 or 300 mg/m2), levothyroxine, atorvastatin, folate, and with B12 every 2 months.Results:At the MTD of 15 mg/m2bexarotene and 15 mg/m2pralatrexate, the response rate was 60% [4 complete responses (CR), 14 partial responses (PR)], the maximum observed response duration was 28.9+ months, and duration of response for 4 CRs ranged from 9.0 to 28.3 months. The median progression-free survival was 12.8 months (0.5-29.9). Mucositis was the most common adverse event.Conclusions:The combination of pralatrexate (15 mg/m2) and oral bexarotene (150 mg/m2) is active with high response rates and minimal toxicity for cutaneous T-cell lymphomas.Clin Cancer Res; 23(14); 3552-6. ©2017 AACR.
University of Texas MD Anderson Cancer Center, Houston, Texas. mduvic@mdanderson.org.
Madeleine
M
Duvic
Stanford University School of Medicine, Stanford, California.
Youn H
YH
Kim
Institute of Hematology "Le A. Seragnoli," University of Bologna, Bologna, Italy.
Pier Luigi
PL
Zinzani
Memorial Sloane Kettering Cancer Center, New York, New York.
Steven M
SM
Horwitz
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000630:Aminopterin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D000077610:Bexarotene; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
C418863:10-propargyl-10-deazaaminopterin; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene; D000630:Aminopterin