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首页> 外文期刊>Journal of oncology pharmacy practice: official publication of the International Society of Oncology Pharmacy Practitioners >Pralatrexate: a novel synthetic antifolate for relapsed or refractory peripheral T-cell lymphoma and other potential uses.
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Pralatrexate: a novel synthetic antifolate for relapsed or refractory peripheral T-cell lymphoma and other potential uses.

机译：Pralatrexate：一种新型的合成抗叶酸药，用于复发或难治的外周T细胞淋巴瘤和其他潜在用途。

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The pharmacology, pharmacokinetics, clinical trials, adverse effects, dosage, and economic considerations of pralatrexate (PDX) are reviewed.Peripheral T-cell lymphoma (PTCL) comprises approximately 15-20% of all aggressive lymphomas and 5-10% of all non-Hodgkin's lymphomas. Advanced PTCL is often refractory to traditional first-line chemotherapy regimens. PDX was developed as a synthetic folate analog antimetabolite that competitively inhibits dihydrofolate reductase (DHFR). This results in the depletion of thymidine, leading to interference with deoxyribonucleic acid synthesis and cancer cell death. PDX has a higher potency than methotrexate and edatrexate (EDX). The efficacy and safety of PDX have been demonstrated in the PROPEL trial, a prospective phase II trial in patients with relapsed or refractory PTCL. Patients with prior stem cell transplantation receiving PDX also had similar response rates (RRs). PDX was investigated on the treatment of relapsed or refractory cutaneous T-cell lymphoma, previously treated advanced non-small cell lung cancer and other solid malignancies. PDX has similar side effects to other DHFR inhibitors. The most common side effect of PDX is mucositis. The recommended dose of PDX is 30 mg/m(2) weekly once for 6 weeks in 7-week cycle until disease progresses or unacceptable toxicity for PTCL and may require dose reduction or discontinuation. Patients should be supplemented with oral folic acid and intramuscular vitamin B(12) injections.PDX provides clinical benefit to patients with relapsed or refractory PTCL with durable complete and partial responses in patients who had not responded to multiple prior treatment regimens.
机译：综述了pralatrexate（PDX）的药理学，药代动力学，临床试验，不良反应，剂量和经济因素。周围性T细胞淋巴瘤（PTCL）约占所有侵袭性淋巴瘤的15-20％，非所有淋巴瘤的5-10％ -霍奇金淋巴瘤。晚期PTCL通常对传统的一线化疗方案无效。 PDX作为合成的叶酸类似物抗代谢物而开发，可竞争性地抑制二氢叶酸还原酶（DHFR）。这导致胸苷的消耗，导致对脱氧核糖核酸合成和癌细胞死亡的干扰。 PDX的效力比甲氨蝶呤和乙草胺酯（EDX）高。 PDX的有效性和安全性已在PROPEL试验中得到证实，该试验是PTCL复发或难治性患者的前瞻性II期试验。先前接受过PDX的干细胞移植的患者也具有相似的缓解率（RR）。对PDX进行了研究，以治疗复发性或难治性皮肤T细胞淋巴瘤，先前治疗的晚期非小细胞肺癌和其他实体恶性肿瘤。 PDX具有与其他DHFR抑制剂相似的副作用。 PDX最常见的副作用是粘膜炎。在7周的周期内，PDX的推荐剂量为每周一次30 mg / m（2），连续6周，直到疾病进展或PTCL的毒性不可接受为止，可能需要降低剂量或停用。患者应补充口服叶酸和肌内维生素B（12）注射.PDX可为PTCL复发或难治性患者提供临床益处，并且对多种先前治疗方案无反应的患者具有持久的完全和部分反应。

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