Harstrick A, Bokemeyer C, Schmoll H J, Köhne-Wömpner C H, Knipp H, Schöffski P, Anagnou J, Wipperman B, Neumann S, Poliwoda H
Department of Hematology/Oncology, University of Hannover Medical School, Federal Republic of Germany.
Cancer Chemother Pharmacol. 1993;31 Suppl 2:S217-21.
Currently, anthracyclines and ifosfamide are the most effective drugs for the treatment of disseminated soft-tissue sarcoma. We designed a treatment protocol of rapidly alternating epirubicin/dacarbazine and ifosfamide for previously untreated soft-tissue sarcoma, whereby 100 mg/m2 epirubicin was given on day 1, 500 mg/m2 dacarbazine was given on days 1 and 2, and 6,000 mg/m2 ifosfamide given via 24-h infusion was begun on day 15. The entire treatment cycle was scheduled to begin again on day 28 if the leukocyte count had reached 3.0 x 10(9)/l. From June 1988 to May 1991, a total of 28 patients were enrolled in the study. Eight patients (31%) achieved a partial response to therapy. The median duration of partial response was 8.5 months, and the median time to progression for all patients was 5 months. Myelosuppression was dose-limiting (leukocyte nadir, 1.7 x 10(9)/l; platelet nadir, 70 x 10(9)/l). Prolonged myelosuppression forced frequent therapy delays; therefore, only 74% of the planned doses could be given. The nonhematologic toxicity was tolerable. This rapidly alternating treatment protocol was determined to offer no therapeutic advantage over anthracycline therapy either alone or in combination with dacarbazine in terms of response rate or time to disease progression. The inclusion of hematopoietic growth factors, however, might ameliorate the dose-limiting myelosuppression and permit the administration of higher doses.
目前，蒽环类药物和异环磷酰胺是治疗播散性软组织肉瘤最有效的药物。我们设计了一种针对既往未接受过治疗的软组织肉瘤的治疗方案，即快速交替使用表柔比星/达卡巴嗪和异环磷酰胺，具体为第1天给予100mg/m²表柔比星，第1天和第2天给予500mg/m²达卡巴嗪，第15天开始通过24小时静脉输注给予6000mg/m²异环磷酰胺。如果白细胞计数达到3.0×10⁹/L，则整个治疗周期计划在第28天再次开始。从1988年6月至1991年5月，共有28例患者纳入该研究。8例患者（31%）对治疗有部分缓解。部分缓解的中位持续时间为8.5个月，所有患者的中位疾病进展时间为5个月。骨髓抑制是剂量限制性的（白细胞最低点，1.7×10⁹/L；血小板最低点，70×10⁹/L）。长期的骨髓抑制导致频繁的治疗延迟；因此，仅能给予计划剂量的74%。非血液学毒性是可耐受的。就缓解率或疾病进展时间而言，这种快速交替治疗方案在单独使用蒽环类药物或与达卡巴嗪联合使用时均未显示出治疗优势。然而，加入造血生长因子可能会改善剂量限制性骨髓抑制并允许给予更高剂量。
