Bramwell V, Van Oosterom A, Mouridsen H T, Cheix F, Somers R, Thomas D, Rozencweig M
Eur J Cancer Clin Oncol. 1982 Jan;18(1):81-4. doi: 10.1016/0277-5379(82)90029-3.
Thirty-six patients with measurable or evaluable advanced soft tissue sarcoma were entered in a phase II trial with PALA. Among the 27 evaluable patients, 15 were men, the median age was 55 yr (16-69) and the median performance status (Karnofsky) was 80 (50-100). Most patients had leiomyosarcoma (8), liposarcoma (3), neurofibrosarcoma (3), synovial cell sarcoma (3), or undifferentiated sarcoma (3). Indicator lesions consisted essentially of lung metastases (21) and/or soft tissue lesions (14). All patients had received prior chemotherapy with 1-5 regimens and 6 had achieved objective response with these previous treatments. PALA was given as a 60-min i.v. infusion at a daily dose of 2.5 g/m2 for two consecutive days. Courses were repeated every two weeks. A median number of 3 courses (2-17) were administered. Partial remission (greater than 50%) was obtained in one patient with a liposarcoma who had also responded to prior combination chemotherapy. This single response to PALA lasted 6 weeks from initiation of therapy. Four patients had unchanged disease after 6+ courses of PALA and 22 had progressive disease. Toxic effects were generally mild to moderate and included cutaneous toxicity (17), diarrhea (14), stomatitis (13), ocular manifestations, consisting of conjunctivitis, corneal ulceration and/or photophobia (11), nausea and vomiting (6) and, possibly, seizures (2). There was no evidence of drug-related myelosuppression. It is concluded that PALA given at the dose schedule selected for this trial has no significant antitumor activity in advanced soft tissue sarcoma previously treated with chemotherapy.
36例患有可测量或可评估的晚期软组织肉瘤的患者进入了一项使用丙氨酰谷氨酰胺（PALA）的II期试验。在27例可评估的患者中，15例为男性，中位年龄为55岁（16 - 69岁），中位体能状态（卡诺夫斯基评分）为80（50 - 100）。大多数患者患有平滑肌肉瘤（8例）、脂肪肉瘤（3例）、神经纤维肉瘤（3例）、滑膜细胞肉瘤（3例）或未分化肉瘤（3例）。指示性病灶主要包括肺转移灶（21个）和/或软组织病灶（14个）。所有患者之前都接受过1 - 5种化疗方案，其中6例在之前的治疗中获得了客观缓解。PALA通过静脉输注60分钟给药，每日剂量为2.5 g/m²，连续两天给药。疗程每两周重复一次。中位给药疗程数为3个（2 - 17个）。一名脂肪肉瘤患者获得了部分缓解（大于50%），该患者之前对联合化疗也有反应。对PALA的这一单一反应从治疗开始持续了6周。4例患者在接受6个以上疗程的PALA治疗后病情无变化，22例患者病情进展。毒性作用一般为轻度至中度，包括皮肤毒性（17例）、腹泻（14例）、口腔炎（13例）、眼部表现，包括结膜炎、角膜溃疡和/或畏光（11例）、恶心和呕吐（6例），可能还有癫痫发作（2例）。没有证据表明存在与药物相关的骨髓抑制。结论是，按照本试验选择的剂量方案给予PALA，对先前接受过化疗的晚期软组织肉瘤没有显著的抗肿瘤活性。
