Hui John, Przespo Eugene, Elefante Anjana
Department of Pharmacy, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
J Oncol Pharm Pract. 2012 Jun;18(2):275-83. doi: 10.1177/1078155211420605. Epub 2011 Sep 26.
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.
综述普拉曲沙（PDX）的药理学、药代动力学、临床试验、不良反应、剂量及经济学考量。
外周T细胞淋巴瘤（PTCL）约占所有侵袭性淋巴瘤的15% - 20%，占所有非霍奇金淋巴瘤的5% - 10%。晚期PTCL通常对传统一线化疗方案耐药。PDX是一种合成叶酸类似物抗代谢药，可竞争性抑制二氢叶酸还原酶（DHFR）。这会导致胸苷耗竭，进而干扰脱氧核糖核酸合成并导致癌细胞死亡。PDX的效力高于甲氨蝶呤和依达曲沙（EDX）。在PROPEL试验（一项针对复发或难治性PTCL患者的前瞻性II期试验）中已证实了PDX的疗效和安全性。先前接受过干细胞移植的患者接受PDX治疗时也有相似的缓解率（RRs）。对PDX还进行了治疗复发或难治性皮肤T细胞淋巴瘤、先前接受过治疗的晚期非小细胞肺癌及其他实体恶性肿瘤的研究。PDX的副作用与其他DHFR抑制剂相似。PDX最常见的副作用是粘膜炎。PDX的推荐剂量为30mg/m²，每周一次，共6周，每7周为一个周期，直至疾病进展或出现不可接受的毒性，对于PTCL可能需要减量或停药。患者应补充口服叶酸和肌肉注射维生素B12。
PDX为复发或难治性PTCL患者带来临床益处，对于此前对多种治疗方案均无反应的患者可产生持久的完全缓解和部分缓解。
