Benjamin R S, Legha S S, Patel S R, Nicaise C
Department of Melanoma-Sarcoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston 77030.
Cancer Chemother Pharmacol. 1993;31 Suppl 2:S174-9.
We have used ifosfamide to treat patients with sarcomas in four completed single-agent protocols and one pilot study since 1985. All the studies have used either N-acetyl-L-cysteine (NAC) or mesna as a uroprotective agent, except in one arm of one study where hydration alone was employed. Mesna has proven superior to NAC in providing protection against ifosfamide-induced hematuria. Mesna given as a loading dose followed by continuous 24-h infusion has been effective and most practical in this regard. Ifosfamide has demonstrated clinically useful antitumor activity in our hands against most sarcoma subtypes. Our studies suggest a dose-response relationship for ifosfamide. At a total dose of 6 g/m2 per course, the overall response rate was 10%; at 10 g/m2 per course, it rose to 21%. Future clinical trials will determine ifosfamide's role in combination chemotherapy and more clearly define the best schedule or schedules for the uroprotective administration of mesna.
自1985年以来,我们已在四项已完成的单药方案和一项试点研究中使用异环磷酰胺治疗肉瘤患者。除了一项研究的一个治疗组仅采用水化治疗外,所有研究均使用N-乙酰半胱氨酸(NAC)或美司钠作为尿路保护剂。在预防异环磷酰胺引起的血尿方面,美司钠已被证明优于NAC。在这方面,给予负荷剂量的美司钠后持续24小时输注是有效的且最为实用。在我们的研究中,异环磷酰胺对大多数肉瘤亚型均显示出临床上有用的抗肿瘤活性。我们的研究表明异环磷酰胺存在剂量反应关系。每疗程总剂量为6 g/m²时,总缓解率为10%;每疗程为10 g/m²时,缓解率升至21%。未来的临床试验将确定异环磷酰胺在联合化疗中的作用,并更明确地确定美司钠尿路保护给药的最佳方案。