Edmonson J H, Kovach J S, Buckner J C, Kvols L K, Hahn R G
Mayo Clinic, Rochester, Minnesota 55905.
Cancer Res. 1988 Nov 15;48(22):6584-6.
24 patients with advanced, histologically proven cancer were treated with difluoromethylornithine 2.25 g/m2 orally every 6 h for the first 7 days of each 4-week treatment cycle. These patients also received daily i.m. doses of recombinant human alpha 2a-interferon (IFN) on Days 3 through 7 of each cycle. IFN doses of 3, 6, 12, 24, 36, and 48 X 10(6) units/m2 have been studied utilizing three patients at each daily dose level. Three additional patients have been observed at each of the two highest doses for better toxicity definition. This combination produced slight transient declines in leukocyte and platelet counts and transient rises in serum aspartate aminotransferase; however, these changes were no more pronounced at the higher IFN doses than at daily doses of 6 X 10(6) units/m2. Mild nausea and vomiting occurred in most patients and mild diarrhea also was common at all IFN dose levels. Chills, fever, myalgia, lethargy and fatigue, and anorexia were also observed at all IFN doses; however, lethargy and fatigue (lassitude) seemed to be the major factor which limited patient tolerance of IFN to 48 X 10(6) units/m2 daily. No ototoxicity was identified clinically or audiometrically and no life-threatening toxicity has occurred. Initial Phase II studies in melanoma are currently in progress.
24例组织学确诊的晚期癌症患者接受二氟甲基鸟氨酸治疗，在每4周治疗周期的前7天，每6小时口服2.25 g/m²。这些患者在每个周期的第3至7天还接受每日一次的重组人α2a干扰素（IFN）肌肉注射。已对每日剂量为3、6、12、24、36和48×10⁶单位/m²的IFN进行了研究，每个剂量水平使用3例患者。在两个最高剂量水平上，又各观察了3例患者以更好地确定毒性。这种联合治疗使白细胞和血小板计数出现轻微短暂下降，血清天冬氨酸转氨酶短暂升高；然而，这些变化在较高IFN剂量下并不比每日剂量为6×10⁶单位/m²时更明显。大多数患者出现轻度恶心和呕吐，在所有IFN剂量水平下轻度腹泻也很常见。在所有IFN剂量下还观察到寒战、发热、肌痛、嗜睡和疲劳以及厌食；然而，嗜睡和疲劳似乎是将患者对IFN的耐受性限制在每日48×10⁶单位/m²的主要因素。临床上或听力测定中未发现耳毒性，也未发生危及生命的毒性。目前正在进行黑色素瘤的初步II期研究。
