Treatment of Transformed Mycosis Fungoides with Intermittent Low-Dose Gemcitabine

Abstract

The malignant helper T cells of mycosis fungoides, a type of cutaneous T cell lymphoma, are capable of transforming into large cerebriform cells. Large cell transformation usually renders the disease more resistant to treatment and prone to relapse. Currently investigated treatment modalities for transformed mycosis fungoides are few and include phototherapy, chemotherapy, biologic response modification, targeted molecular therapy and combinations thereof. A tolerable and reliable modality has yet to be identified. Gemcitabine, a novel purine analogue, is gaining recognition as a potent agent for advanced nontransformed cutaneous T cell lymphoma. Here we present a brief review of the literature with 3 illustrative cases that additionally reveal gemcitabine monotherapy to be a practical, safe and efficacious option for mycosis fungoides that has undergone large cell transformation.

Outcomes of Patients with Transformed Mycosis Fungoides: Analysis from a Prospective Multicenter US Cohort Study

“…Awar et al showed that gemcitabine was effective in several patients. 7 Pralatrexate, a novel folate analog, was shown to be active in a prospective clinical trial (PROPEL) in which tMF patients were enrolled. 12 Patients received pralatrexate at a dose of 30 mg/m 2 weekly x 6 weeks on a 7-week schedule.…”

“…6 tMF is defined as the appearance of large atypical cells on the skin or in nodes that exceed 25% of infiltrating atypical T-cells or clusters of large cells with nuclei that are > 4 times the normal size. 7,8 Transformation of MF is associated with a more rapidly progressive, aggressive disease course and poor median survival, ranging from 1 to 4 years from the time of transformation, despite the use of aggressive chemotherapy. [9][10][11][12] The predictive factors associated with patient survival in tMF are unclear and have included CD30 expression, lactate dehydrogenase (LDH), sites of disease, and time of transformation after onset of MF.…”

Practical Management of CD30+ Lymphoproliferative Disorders

“…78 In this study of 3 patients, doses ranged from 750 to 1000 mg/m 2 given by typical regimen on days 1, 8, and 15 of a 28-day cycle and also by dosing from every other week to even more intermittent dosing when needed based on tumor growth. Grade 3 thrombocytopenia was noted in 1 patient, and all 3 patients experienced grade 4 neutropenia requiring treatment with granulocyte-macrophage colony-stimulating factor.…”

The Discovery of Polo-Like Kinase 4 Inhibitors: Identification of (1R,2S)-2-(3-((E)-4-(((cis)-2,6-Dimethylmorpholino)methyl)styryl)-1H-indazol-6-yl)-5′-methoxyspiro[cyclopropane-1,3′-indolin]-2′-one (CFI-400945) as a Potent, Orally Active Antitumor Agent

“…There are theoretical reasons to suppose that antimitotic agents can better exert their effects on tumor growth inhibition by employing an intermittent dosing regimen, and some chemotherapeutic agents perform optimally on such schedules. − Accordingly, the maximum tolerated dose (MTD) for compounds 46 , 47 , and 48 for a 1-on/3-off schedule were estimated to be 39, 36, and 39 mg/kg, respectively. Thus, we were able to increase the total compound dosed over the 21 day experiment from 197.4 mg/kg for 9.4 mg/kg (QD regimen) to 252 and 273 mg/kg for the 36 and 39 mg/kg (1-on/3-off regimen) respectively.…”

“…Diethyl ether (200 mL) was added, and the precipitate was collected by filtration to give a yellow solid (5.6 g, 52%). 1 (48). To a solution of 18a (20 g, 46 mmol) and (E)-4-(4-(2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)vinyl)benzyl)morpholine (18.2 g, 51 mmol) in dioxane (400 mL) and water (80 mL) was added Na 2 CO 3 (9.8 g, 92.8 mmol) and Pd(PPh 3 ) 4 (1.61 g, 1.39 mmol).…”