Anthony L, Johnson D, Hande K, Shaff M, Winn S, Krozely M, Oates J
Department of Medicine and Radiology, Vanderbilt University, Nashville, TN 37232-5536.
Acta Oncol. 1993;32(2):217-23. doi: 10.3109/02841869309083915.
To further investigate the antineoplastic efficacy and safety of somatostatin analogues, 2 trials were performed. Octreotide, SMS 201-995 (Sandostatin), was escalated in doses ranging from 1,500 micrograms to 6,000 micrograms daily in 14 patients with carcinoid. Somatuline, (BIM 23014C, Angiopeptin, Lanreotide) was given in doses ranging from 2,250 micrograms to 9,000 micrograms daily to 13 neuroendocrine patients (6 carcinoid, 2 atypical carcinoid, 3 pancreatic islet cell and 2 small cell lung cancer patients). All patients successfully completed dose escalations without significant adverse effects and were evaluable for toxicity. The dose limiting side-effect of octreotide was the injection volume. No dose limiting adverse effects have been observed with somatuline. Carcinoid syndrome symptoms were better controlled with higher octreotide doses. Thirteen patients were evaluable for octreotide's antitumor efficacy with a partial response observed in 4 (31%), stable disease in 2 and progressive disease in 7 patients. Radiographic changes of increased tumor necrosis occurred in 5 patients and was independent of response. Somatuline resulted in a partial response in 4 patients (2 carcinoids, 1 gastrinoma and 1 small cell lung cancer) (31%), stable disease in 1 atypical carcinoid, and progressive disease in 8 (4 carcinoid, 1 atypical carcinoid, 2 islet cell and 1 multi-drug resistant small cell lung cancer). Six of the 8 carcinoid patients had radiographic changes of increased necrosis. Dose escalation of somatostatin analogues is well tolerated and may be associated with antitumor activity in some neuroendocrine neoplasms.
为进一步研究生长抑素类似物的抗肿瘤疗效和安全性，进行了2项试验。在14例类癌患者中，奥曲肽（SMS 201-995，善宁）的剂量从每日1500微克递增至6000微克。在13例神经内分泌患者（6例类癌、2例非典型类癌、3例胰岛细胞瘤和2例小细胞肺癌患者）中，索马杜林（BIM 23014C，血管活性肠肽，兰瑞肽）的剂量为每日2250微克至9000微克。所有患者均成功完成剂量递增，无明显不良反应，且可评估毒性。奥曲肽的剂量限制性副作用是注射体积。未观察到索马杜林有剂量限制性不良反应。较高剂量的奥曲肽能更好地控制类癌综合征症状。13例患者可评估奥曲肽的抗肿瘤疗效，4例（31%）出现部分缓解，2例病情稳定，7例病情进展。5例患者出现肿瘤坏死增加的影像学改变，且与反应无关。索马杜林使4例患者（2例类癌、1例胃泌素瘤和1例小细胞肺癌）出现部分缓解（31%），1例非典型类癌病情稳定，8例（4例类癌、1例非典型类癌、2例胰岛细胞瘤和1例多药耐药小细胞肺癌）病情进展。8例类癌患者中有6例出现坏死增加的影像学改变。生长抑素类似物的剂量递增耐受性良好，可能与某些神经内分泌肿瘤的抗肿瘤活性有关。
