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.