Methods for extending progression-free survival using 10-propargyl-10-deazaaminopterin
A technology of heteroaminopterin and heteroaminopterin, which is applied in the field of 10-propargyl-10-deazaaminopterin therapy for cancer, can solve problems such as resistance and shortening of remission time.
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Embodiment 1
[0060] figure 1 A synthetic scheme for the preparation of 10-propargyl-10-deazaminopterin is shown. A mixture of 60% NaH (1.06 g, 26.5 mmol) in 18 mL of molecular sieve-dried oil dispersion in THF was cooled to 0°C. Dimethyl terephthalate (5.0 g, figure 1 A solution of 24 mmol of compound 1) was treated in , and the mixture was stirred at 0° C. for 1 hour. Allyl bromide (26.4 mmol) was added, and the mixture was stirred at 0°C for an additional 1 hour and then at room temperature for 16 hours. The resulting mixture was treated with 2.4 mL of 50% acetic acid and then poured into 240 mL of water. The mixture was extracted with ether (2X150 mL). Combine the ether extracts in Na 2 SO 4 dried and concentrated to an orange-yellow oil. Chromatography on silica gel (600 mL 230-400 mesh) eluting with cyclohexane-EtOAc (8:1) gave the product α-allyl dimethyl terephthalate (compound 2) as a white solid ( 4.66), which was homogeneous by TLC (cyclohexane-EtOAc, 3:1). However, mass...
Embodiment 2
[0068] Analysis of progressive resistance. Treatment immediately prior to entering clinical trial PDX-008 provided data from a heterogeneous control group reflecting clinical practice that was used to compare the efficacy of pralatrexate. This data set benefited from being derived from the same patients as those receiving pralatrexate and thus avoided inter-subject variability.
[0069] Across a wide range of malignancies, including non-Hodgkin's lymphoma (NHL), treatment-naive patients often show greater responses to chemotherapy than those who receive second-line or subsequent therapy. In addition, objective response rate (ORR) and progression-free survival (PFS) generally decline with each subsequent line of therapy (markers of acquired resistance). This trend was also expected for PTCL, although there are no published studies or retrospective data analyzes in PTCL specifically describing the pattern of response to continuous therapy. The objectives of the analyzes presen...
Embodiment 3
[0104] Pralatrexate is effective in patients with relapsed / refractory peripheral T-cell lymphoma (PTCL) after treatment with ifosfamide, carboplatin, and etoposide (ICE)-based regimens
[0105] Background: The prognosis of invasive PTCL is bleak. Investigators have developed rescue protocols in an attempt to improve outcomes for patients with relapsed or refractory disease. One such regimen that is frequently used is ifosfamide, carboplatin, and etoposide (ICE) or ICE-based regimens (eg, together with rituximab-ICE [RICE] and dexamethasone-ICE [DICE ]). These regimens can have response rates approaching 70% and patients can go on to receive stem cell transplantation, however most patients tend to relapse rapidly (Horwitz et al. Blood 2005;106:a2679). Therefore, optimal approaches for patients with relapsed or refractory disease are needed, and drugs based on unique mechanisms of action warrant research. This analysis was performed to determine whether pralatrexate provided ...
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