A DOSE-FINDING STUDY OF LANREOTIDE (A SOMATOSTATIN ANALOG) IN PATIENTS WITH COLORECTAL-CARCINOMA

BACKGROUND. Laboratory data suggest that insulin-like growth factor-1 (IGF-1) may stimulate the growth of different human tumors. At least i n acromegalic patients, somatostatin (SMS) analogs, such as lanreotide , suppress the serum levels of growth hormone (GH) and IGF-1. METHODS. To evaluate the tolerability and biologic activity of different doses of lanreotide in patients with advanced colorectal carcinoma, consecu tive groups of 3 patients each were subcutaneous treated with lanreoti de at doses of 1, 2, 3, 4, 5, or 6 mg three times a day for 2 months. In the event of Grade 3 side effects, 3 additional patients were treat ed with the same dose before the next dose escalation. Serum samples w ere obtained on Days 0, 15, 30, and 60 for serum GH, IGF-1, and lanreo tide assessment. RESULTS. Twenty-four patients were enrolled and all w ere evaluable. Except for the 3 and 6 mg doses, for which the observat ion of a Grade 3 side effect required that an additional three patient s be treated, it was sufficient to treat 3 patients at each dose. The overall incidence of side effects was as follows: changes in bowel hab its, 83%; abdominal cramps, 79%; diarrhea, 17%; vomiting, 17%; nausea, 21%; steatorrhea, 78%; hyperglycemia, 35%; laboratory hypothyroidism, 39%; gallstones, 13%; and weight loss, 17%. No evidence of an increas e in the incidence, intensity, or duration of side effects was observe d with dose escalation. Serum IGF-1 levels were as follows: Day 15: 63 %, 60%, and 67% of the baseline values for the low (1-2 mg), intermedi ate (3-4 mg), and high (5-6 mg) dose groups, respectively; Day 30: 63% , 59%, and 51%, respectively; and Day 60: 73%, 69%, and 47%, respectiv ely. Serum lanreotide levels declined during treatment in all of the d ose groups (90 ng/mL on Day 15, and 35 ng/mL on Day 60 for the 5-6 mg group; 10 ng/mL on Day 15, and 1.5 ng/mL on Day 60 for the 1-2 mg grou p). No antitumor activity or tumor marker reduction was observed. CONC LUSIONS. No increase in toxicity was observed when subcutaneous lanreo tide doses were escalated to 6 mg three times a day for 2 months. The highest doses seemed to maintain reduced serum IGF-1 levels; with the lowest doses, a ''rebound'' in serum IGF-1 levels was observed during treatment. Nevertheless, intermittent subcutaneous injections do not e nsure constant serum drug concentrations over time. (C) 1996 American Cancer Society.