Warrell R P, Coonley C J, Straus D J, Young C W
Cancer. 1983 Jun 1;51(11):1982-7. doi: 10.1002/1097-0142(19830601)51:11<1982::aid-cncr2820511104>3.0.co;2-l.
Previous trials of gallium nitrate (NSC-15200) showed that bolus administration produced dose-limiting nephrotoxicity without substantial antitumor activity. As an effort to increase the therapeutic index of this compound and to establish a satisfactory out-patient schedule, the authors evaluated the effects of gallium nitrate administered as a continuous infusion in patients with advanced malignant lymphoma. In an initial Phase I trial, four dose levels which ranged from 200 to 400 mg/m2/day in 27 patients were studied. Nausea which impaired oral hydration was found to be dose-limiting. A dose of 300 mg/m2/day was chosen for extended Phase II evaluation and 37 additional patients were entered into the study at that dose level. Overall, 16 of 47 patients (34%) who had bi-dimensionally measurable parameters of disease achieved major antitumor responses (six of 15 with diffuse "histiocytic" lymphoma, five of ten with diffuse poorly-differentiated lymphocytic lymphoma, two of five with nodular poorly-differentiated lymphocytic lymphoma, and three of 17 with Hodgkin's disease). The median duration of response was 2.5 months. Only 8% of patients who received 300 mg/m2/day developed an increase in serum creatinine concentration greater than 1.1 mg/dl over baseline values. Hypocalcemia occurred in two-thirds of patients. Other toxic effects, including paresthesiae, diarrhea, and hearing loss, were noted in less than 5% of patients. There was minimal myelosuppression. The authors conclude that gallium nitrate administered as a continuous infusion for seven days at 300 mg/m2/day is well-tolerated and effective treatment for patients with advanced malignant lymphoma. Outpatient administration using portable infusion pumps is safe and practical. Further evaluation of the drug administered as a constant infusion is indicated in patients with other neoplastic diseases.
先前硝酸镓（NSC - 15200）的试验表明，大剂量推注给药会产生剂量限制性肾毒性，且无显著抗肿瘤活性。为提高该化合物的治疗指数并制定令人满意的门诊给药方案，作者评估了晚期恶性淋巴瘤患者持续输注硝酸镓的效果。在最初的I期试验中，对27例患者进行了研究，剂量水平为200至400mg/m²/天，分四个剂量组。发现影响口服补液的恶心是剂量限制性因素。选择300mg/m²/天的剂量进行扩展II期评估，另外37例患者以该剂量水平进入研究。总体而言，47例具有二维可测量疾病参数的患者中有16例（34%）获得了主要抗肿瘤反应（15例弥漫性“组织细胞性”淋巴瘤中有6例，10例弥漫性低分化淋巴细胞性淋巴瘤中有5例，5例结节性低分化淋巴细胞性淋巴瘤中有2例，17例霍奇金病中有3例）。反应的中位持续时间为2.5个月。接受300mg/m²/天治疗的患者中，只有8%的患者血清肌酐浓度较基线值升高超过1.1mg/dl。三分之二的患者出现低钙血症。其他毒性作用，包括感觉异常、腹泻和听力丧失，在不到5%的患者中出现。骨髓抑制轻微。作者得出结论，对于晚期恶性淋巴瘤患者，以300mg/m²/天持续输注7天的硝酸镓耐受性良好且有效。使用便携式输液泵进行门诊给药安全且实用。对于其他肿瘤性疾病患者，建议进一步评估持续输注该药物的效果。
