Rozencweig M, Nicaise C, Beer M, Crespeigne N, Van Rijmenant M, Lenaz L, Kenis Y
J Clin Oncol. 1983 Oct;1(10):621-6. doi: 10.1200/JCO.1983.1.10.621.
Twenty-six adult patients were entered in a phase I trial of carboplatin, a new cisplatin derivative with reduced potential for nephrotoxicity. All patients had solid tumors and the median World Health Organization performance score was 2 (0-3). Twelve patients had not received prior chemotherapy. The drug was administered as a 15-minute IV infusion, without pre- or posthydration, at daily doses of 40-125 mg/m2 for five consecutive days. Antiemetics were given only if needed. Thrombocytopenia and neutropenia were dose related and dose limiting. One patient died from septic shock at the highest dose level. Nonhemolytic anemia was also encountered. Nausea and vomiting were experienced by most patients but gastrointestinal intolerance was severe in only two patients. One patient had hypercreatininemia, which was minor and rapidly reversible. Other toxic effects consisted of negligible fatigue, paresthesia, pruritus, local pain, stomatitis, headache, and alopecia. Although none of the patients achieved a partial or complete response, antitumor effect was strongly suggested in two patients with thyroid and cervix cancer, respectively. Carboplatin is an attractive candidate for phase II trials. In good-risk patients, such trials could be initiated at a daily dose of 100 mg/m2 for five consecutive days every five to six weeks.
26名成年患者进入了卡铂的I期试验,卡铂是一种新的顺铂衍生物,肾毒性潜力降低。所有患者均患有实体瘤,世界卫生组织表现评分中位数为2(0 - 3)。12名患者未曾接受过先前的化疗。该药物通过静脉输注15分钟给药,无需水化预处理或后处理,连续五天每日剂量为40 - 125mg/m²。仅在需要时给予止吐药。血小板减少和中性粒细胞减少与剂量相关且为剂量限制性。一名患者在最高剂量水平死于感染性休克。还出现了非溶血性贫血。大多数患者经历了恶心和呕吐,但只有两名患者胃肠道不耐受严重。一名患者出现高肌酐血症,程度较轻且迅速可逆。其他毒性作用包括可忽略不计的疲劳、感觉异常、瘙痒、局部疼痛、口腔炎、头痛和脱发。尽管没有患者达到部分或完全缓解,但分别在两名甲状腺癌和宫颈癌患者中强烈提示有抗肿瘤作用。卡铂是II期试验的一个有吸引力的候选药物。对于风险较低的患者,此类试验可以每五到六周连续五天每日剂量100mg/m²开始。