DOSE-INTENSIVE CHEMOTHERAPY IN REFRACTORY GERM-CELL CANCER - A PHASE-I/II TRIAL OF HIGH-DOSE CARBOPLATIN AND ETOPOSIDE WITH AUTOLOGOUS BONE-MARROW TRANSPLANTATION
DOSE-INTENSIVE CHEMOTHERAPY IN REFRACTORY GERM-CELL CANCER - A PHASE-I/II TRIAL OF HIGH-DOSE CARBOPLATIN AND ETOPOSIDE WITH AUTOLOGOUS BONE-MARROW TRANSPLANTATION
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DOI：
10.1200/jco.1989.7.7.932
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发表时间：
1989-07-01
影响因子：
45.3
通讯作者：
JANSEN, J
中科院分区：
文献类型：
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作者：
NICHOLS, CR;TRICOT, G;JANSEN, J
1986年9月至1988年3月，33例难治性生殖细胞癌患者进入了I/II期试验，两个疗程的高剂量卡铂加依托泊苷与自体骨髓支持。所有患者均接受过广泛的既往治疗，并且患有顺铂难治性疾病（67%），定义为末次顺铂给药后4周内进展，或者至少两种基于顺铂的方案（35%）失败，包括顺铂-异环磷酰胺挽救方案。患者在每个周期接受固定总剂量的依托泊苷1，200 mg/m2。卡铂剂量范围为900 mg/m2至2，000 mg/m2。33例患者中有20例接受了第二个周期的治疗。尽管既往接受过顺铂的广泛治疗，但大剂量卡铂和依托泊苷的神经毒性、肾毒性或听力损伤并不常见。最常见的非血液学毒性是中度小肠结肠炎。在每个剂量水平下，该方案的血液学毒性均显著。所有53个疗程均伴有粒细胞减少性发热。33例患者中有7例（21%）死于治疗。所有这些死亡都发生在粒细胞最低点期间，其中5例与记录的脓毒症有关。总体而言，32例可评价缓解的患者中有14例（44%）获得了客观缓解，包括8例完全缓解。4例患者保持完全缓解，3例患者连续无病超过1年。8例缓解者（包括4例完全缓解）在接受顺铂治疗期间发生进展。我们认为，卡铂和依托泊苷可以在高剂量联合给药，这种方案可能有治愈生殖细胞肿瘤患者耐常规剂量顺铂为基础的治疗潜力。
Between September 1986 and March 1988, 33 patients with refractory germ cell cancer were entered on a phase I/II trial of two courses of high-dose carboplatin plus etoposide with autologous bone marrow support. All patients had extensive prior treatment and had either cisplatin-refractory disease (67%) defined as progression within 4 weeks of the last cisplatin dose or failed at least two cisplatin-based regimens (35%) including a cisplatin-ifosfamide salvage regimen. Patients received a fixed total dose of etoposide of 1,200 mg/m2 with each cycle. The carboplatin dose ranged from 900 mg/m2 to 2,000 mg/m2. Twenty of the 33 patients received the second cycle of therapy. Despite extensive prior therapy with cisplatin, neurotoxicity, nephrotoxicity, or hearing impairment with high-dose carboplatin and etoposide was unusual. The most common nonhematologic toxicity was moderate enterocolitis. The hematologic toxicity of this regimen was substantial at each dose level. All 53 courses were accompanied by granulocytopenic fevers. Seven of the 33 patients (21%) died from treatment. All of these deaths occurred during the granulocyte nadir, and five were related to documented sepsis. Overall, 14 of 32 patients (44%) evaluable for response obtained an objective response, including eight complete remissions. Four patients remain in complete remission, with three patients being continuously free of disease in excess of 1 year. Eight responders (including four complete remissions) had progressed while receiving cisplatin. We concude that carboplatin and etoposide can be administered in combination at high dosages and this regimen may have curative potential for patients with germ cell tumors resistant to conventional-dose cisplatin-based therapies.