Sarosy G, Leyland-Jones B, Soochan P, Cheson B D
Investigational Drug Branch, National Cancer Institute, Bethesda, MD 20892.
J Clin Oncol. 1988 Nov;6(11):1768-82. doi: 10.1200/JCO.1988.6.11.1768.
Melphalan (L-phenylalanine mustard) is a bifunctional alkylating agent that is commonly administered orally to treat a wide variety of malignancies, including cancers of the breast and ovary, as well as multiple myeloma. Although commercially available in Europe and Canada, intravenous (IV) melphalan remains investigational in the United States. The role of IV melphalan in cancer chemotherapy is not well defined, despite its manageable toxicity and higher and more predictable blood levels following IV administration compared with oral administration. In addition, unlike oral melphalan, an extensive phase I evaluation of IV melphalan has not been undertaken. At lower doses (eg, 30 to 70 mg/m2), both as a single agent and in combination, the activity of IV melphalan has been evaluated in only a limited number of diseases. However, striking activity has been observed in previously untreated patients with rhabdomyosarcoma, a disease not generally considered responsive to alkylating agents. When administered at high doses (greater than 140 mg/m2) requiring bone marrow reinfusion, melphalan effects a high response rate (but no improvement in survival) in a variety of nonhematologic tumor types, including resistant tumors such as melanoma and colon carcinoma. In contrast, in poor-prognosis patients with non-Hodgkin's lymphoma, Hodgkin's disease, multiple myeloma, or neuroblastoma, high-dose melphalan-containing regimens have yielded both high response rates and improved survival, despite considerable toxicity. Additional clinical trials will be necessary to define the spectrum of activity of lower doses of IV melphalan and to define subgroups of patients most likely to benefit from high-dose melphalan.
美法仑（L-苯丙氨酸氮芥）是一种双功能烷化剂，通常口服用于治疗多种恶性肿瘤，包括乳腺癌、卵巢癌以及多发性骨髓瘤。尽管在欧洲和加拿大有上市，但静脉注射美法仑在美国仍处于研究阶段。尽管静脉注射美法仑的毒性易于控制，且与口服给药相比，静脉注射后血药浓度更高且更可预测，但其在癌症化疗中的作用仍未明确界定。此外，与口服美法仑不同，尚未对静脉注射美法仑进行广泛的Ⅰ期评估。在较低剂量（如30至70mg/m²）下，无论是单药使用还是联合使用，仅在少数疾病中评估了静脉注射美法仑的活性。然而，在横纹肌肉瘤初治患者中观察到了显著活性，横纹肌肉瘤通常不被认为对烷化剂有反应。当以需要骨髓回输的高剂量（大于140mg/m²）给药时，美法仑在多种非血液系统肿瘤类型中产生高缓解率（但生存期无改善），包括黑色素瘤和结肠癌等耐药肿瘤。相比之下，在预后不良的非霍奇金淋巴瘤、霍奇金病、多发性骨髓瘤或神经母细胞瘤患者中，尽管毒性较大，但含高剂量美法仑的方案既产生了高缓解率，又改善了生存期。需要进行更多的临床试验来确定低剂量静脉注射美法仑的活性谱，并确定最可能从高剂量美法仑中获益的患者亚组。
