PHASE-II STUDIES OF SINGLE-AGENT CIMETIDINE AND THE COMBINATION N-PHOSPHONACETYL-L-ASPARTATE (NSC-224131) PLUS L-ALANOSINE (NSC-153353) IN ADVANCED MALIGNANT-MELANOMA
PHASE-II STUDIES OF SINGLE-AGENT CIMETIDINE AND THE COMBINATION N-PHOSPHONACETYL-L-ASPARTATE (NSC-224131) PLUS L-ALANOSINE (NSC-153353) IN ADVANCED MALIGNANT-MELANOMA
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DOI：
10.1200/jco.1987.5.7.1078
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发表时间：
1987-07-01
影响因子：
45.3
通讯作者：
CHANG, M
中科院分区：
文献类型：
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作者：
MORTON, RF;CREAGAN, ET;CHANG, M
我们在40例未经治疗的活检证实的、可测量的播散性恶性黑色素瘤患者中进行了西咪替丁单药治疗和N-膦酰乙酰-L-丙氨酸（PALA）+L-丙氨酸核苷联合治疗的平行II期试验。我们并没有将试验设计为对两种方案的比较评估。在19例接受西咪替丁300 mg口服每日4次治疗的患者中，有1例广泛胸膜和肺转移完全缓解，持续16个月以上，2例软组织病变部分消退，分别持续7个月和21个月以上。在21例接受联合方案治疗的患者中，只有1例软组织部分缓解，持续1个月。西咪替丁组的中位进展时间和死亡时间分别为1.4和6个月，而PALA + L-丙氨酸核苷联合治疗组分别为1.3和4个月。在初始治疗进展的患者中，12名接受西咪替丁交叉治疗的患者和11名接受联合治疗的患者没有反应。两名接受联合治疗的患者发生了严重的口腔炎，两名发生了肾衰竭，一名发生了严重的白细胞减少和血小板减少。认识到小样本量的局限性，这些早期的观察结果表明，西咪替丁可能在播散性恶性黑色素瘤的管理有有趣的意义。
We conducted parallel phase II trials of cimetidine as a single agent and the combination N-phosphonacetyl-L-asparate (PALA) plus L-alanosine among 40 previously untreated patients with biopsy-proven, measurable disseminated malignant melanoma. We did not design the trial to be a comparative assessment of the two regimens. Among 19 patients treated with cimetidine, 300 mg orally four times daily, there was one complete response of extensive pleural and pulmonary metastases for 16+ months and two partial regressions of soft tissue lesions for 7 and 21+ months, respectively. Among 21 patients treated with the combination regimen, there was only one partial response in soft tissue for 1 month. The median times to progression and death were 1.4 and 6 months, respectively, for cimetidine, and 1.3 and 4 months, respectively, from the combination of PALA plus L-alanosine. Among patients who progressed on initial treatment, there were no responses in 12 who received crossover therapy with cimetidine and 11 with the combination regimen. Two patients treated with the combination program had severe stomatitis, two developed renal failure, and one had severe leukopenia and thrombocytopenia. Recognizing the limitations of small sample size, these early observations suggest that cimetidine may have intriguing implications in the management of disseminated malignant melanoma.