PHASE-II STUDY OF DEOXYSPERGUALIN IN METASTATIC BREAST-CANCER
PHASE-II STUDY OF DEOXYSPERGUALIN IN METASTATIC BREAST-CANCER
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DOI：
10.1007/bf00873965
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发表时间：
1994-01-01
影响因子：
3.4
通讯作者：
HORTOBAGYI, G
中科院分区：
文献类型：
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作者：
DHINGRA, K;VALERO, V;HORTOBAGYI, G
我们对一线化疗失败的转移性乳腺癌患者进行了新型免疫调节/细胞毒性药物 15-脱氧精胍菌素的 II 期试验。参加本试验的 14 名患者接受了 38 个疗程的治疗，其中 25 名患者的剂量为 1800 mg/m(2)/d（剂量水平 0），13 名患者的剂量为 2150 mg/m(2)/d（剂量水平+1），连续静脉输注 5 天。治疗耐受性良好，分别在两个和三个疗程中出现神经肌肉副作用（肌痛、感觉异常）和粒细胞减少症（粒细胞计数最低点为 0.50-0.99x10(9)/1），这是唯一的 III 级毒性。脱氧精胍菌素的神经肌肉毒性可能与低镁血症的发生有关。本研究中未观察到部分或完全反应。一名患者获得了轻微缓解，但在入组后 65 周病情进展。观察到该反应与外周血中 T4/T8 比率的增加同时发生。整个队列的中位进展时间为八周（范围为 4-65 周）。没有免疫抑制的临床证据，也没有观察到外周血淋巴细胞总数或辅助 T 细胞减少。按照本试验中采用的剂量和时间表，脱氧精胍菌素似乎对一线化疗耐药的转移性乳腺癌没有显着的活性。低镁血症和脱氧精胍菌素的神经肌肉毒性之间的相关性是一个有趣的、以前未知的观察结果，需要进一步研究。
We conducted a phase II trial of the novel immunomodulatory/cytotoxic agent 15-deoxyspergualin in patients with metastatic breast cancer who had failed treatment with front-line chemotherapy. Thirty-eight courses of treatment were administered to fourteen patients enrolled in this trial, 25 at a dose of 1800 mg/m(2)/d (dose level 0) and 13 at a dose of 2150 mg/m(2)/d (dose level +1) administered by continuous intravenous infusion for 5 days. Treatment was well tolerated with neuromuscular side-effects (myalgias, paresthesias) and granulocytopenia (nadir granulocyte count of 0.50-0.99x10(9)/1) in two and three courses, respectively, as the only grade III toxicities. The neuromuscular toxicity of deoxyspergualin is probably related to the occurrence of hypomagnesemia. No partial or complete responses were observed in this study. One patient achieved a minor response but had progressive disease 65 weeks after enrollment. The response was observed coincident with an increase in T4/T8 ratio in the peripheral blood. The median time to progression for the entire cohort was eight weeks (range, 4-65 weeks). There was no clinical evidence of immunosuppression and no decrease in total peripheral blood lymphocyte counts or helper T-cells was observed. At the doses and schedule employed in this trial, deoxyspergualin does not appear to have significant activity against metastatic breast cancer resistant to front-line chemotherapy. The correlation between hypomagnesemia and neuromuscular toxicity of deoxyspergualin is an intriguing, previously unknown observation and requires further investigation.