Meyers F J, Welborn J, Lewis J P, Flynn N
Department of Medicine, University of California, Davis Medical Center, Sacramento.
J Clin Oncol. 1989 Feb;7(2):173-8. doi: 10.1200/JCO.1989.7.2.173.
Carboplatin (CBDCA) is a second-generation platinum analog with prominent myelotoxicity and modest extramedullary toxicity. We performed a phase I study of CBDCA in adult patients with relapsed acute leukemia. Therapy was administered as a five-day continuous infusion. The initial dose of 875 mg/m2 over five days was escalated in 15% increments to a final dose of 2,100 mg/m2 over five days. Twenty-eight patients received 35 induction courses of CBDCA, including two patients who achieved a complete remission (CR) following the first course, and received a second induction course at the time of relapse. Therapy was well tolerated. No grade 3 or 4 extramedullary toxicity was seen. Myelosuppression was regularly observed, with prolonged myelosuppression at 2,100 mg/m2 over five days being the indication to cease dose escalation. Eight of 28 patients (28.5%) responded to CBDCA therapy (six CR, two partial remission [PR]) or ten of 30 initial induction courses (33.3%). Continuous-infusion CBDCA has an advantage over other therapy for acute leukemia because of its highly selective myelotoxicity and minimal gastrointestinal and renal toxicity. A standard phase II study should be undertaken to establish a more accurate response rate.
卡铂（CBDCA）是一种第二代铂类类似物，具有显著的骨髓毒性和适度的髓外毒性。我们对复发的成年急性白血病患者进行了卡铂的I期研究。治疗采用为期五天的持续静脉输注给药。初始剂量为875mg/m²，持续五天，以15%的增幅递增，最终剂量为2100mg/m²，持续五天。28例患者接受了35个周期的卡铂诱导治疗，其中包括2例在第一个疗程后达到完全缓解（CR）的患者，并在复发时接受了第二个诱导疗程。治疗耐受性良好。未观察到3级或4级髓外毒性。骨髓抑制经常出现，五天内2100mg/m²剂量时出现的长时间骨髓抑制是停止剂量递增的指征。28例患者中有8例（28.5%）对卡铂治疗有反应（6例CR，2例部分缓解[PR]），或30个初始诱导疗程中有10个（33.3%）有反应。持续静脉输注卡铂治疗急性白血病优于其他疗法，因为其具有高度选择性的骨髓毒性以及最小的胃肠道和肾脏毒性。应开展标准的II期研究以确定更准确的缓解率。
