Hilal E Y, Pinsky C M, Hirshaut Y, Wanebo H J, Hansen J A, Braun D W, Fortner J G, Oettgen H F
Cancer. 1981 Jul 15;48(2):245-51. doi: 10.1002/1097-0142(19810715)48:2<245::aid-cncr2820480206>3.0.co;2-h.
The authors' previous surgical adjuvant trial in patients with malignant melanoma at high risk of recurrence has shown no difference in disease-free interval or survival between patients randomized to surgery + BCG or surgery alone. Reported here is a subsequent nonrandomized trial in 30 similar patients who received surgery + Corynebacterium parvum (CP) 4 mg I.V. daily x 5, followed by 4 mg S.C. weekly for up to three years. After I.V. C. parvum, chills, fever, headache, and hypertension were common. After S.C. C. parvum, varying degrees of local induration, erythema, and pain were experienced. Dose reduction was necessary for 14 patients during I.V. treatment and for six patients during S.C. treatment. A marked decrease in absolute lymphocyte count and a decreased proliferative response of lymphocytes to common antigens in vitro was observed after 2-3 days of I.V. C. parvum. Lymphocyte reactivity to mitogens decreased, particularly with Con A. Marked increase in nitroblue tetrazolium reduction by granulocytes was seen in 20 patients. Although changes in delayed cutaneous hypersensitivity reactions to recall antigens followed no consistent pattern, reactivity to DNCB increased in 18 patients. In addition, median time to recurrence was 33 weeks, significantly shorter than in the previous trial, but the survival distribution was no different from before. It can be concluded, therefore, that the administration of C. parvum in this dose and schedule had essentially no effect on the outcome of these patients.
作者之前针对复发风险高的恶性黑色素瘤患者进行的手术辅助试验表明，随机分配至手术 + 卡介苗组或单纯手术组的患者在无病间期或生存率方面没有差异。本文报告了一项后续的非随机试验，该试验纳入了30例类似患者，他们接受了手术 + 小棒状杆菌（CP）治疗，静脉注射4毫克，每日1次，共5天，随后皮下注射4毫克，每周1次，持续长达三年。静脉注射CP后，寒战、发热、头痛和高血压很常见。皮下注射CP后，患者出现了不同程度的局部硬结、红斑和疼痛。14例患者在静脉注射治疗期间需要减量，6例患者在皮下注射治疗期间需要减量。静脉注射CP 2 - 3天后，观察到绝对淋巴细胞计数显著下降，淋巴细胞对常见抗原的体外增殖反应降低。淋巴细胞对丝裂原的反应性降低，尤其是对刀豆蛋白A的反应。20例患者的粒细胞硝基蓝四氮唑还原能力显著增加。尽管对回忆抗原的迟发性皮肤超敏反应变化没有一致的模式，但18例患者对二硝基氯苯的反应性增加。此外，复发的中位时间为33周，明显短于之前的试验，但生存分布与之前没有差异。因此，可以得出结论，以这种剂量和方案给予CP对这些患者的预后基本上没有影响。
