Background:
Laboratory data suggest that insulin-like growth factor-1 (igf-1) may stimulate the growth of different human tumors. at least in 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, consecutive groups of 3 patients each were subcutaneous treated with lanreotide 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 treated with the same dose before the next dose escalation. serum samples were obtained on days 0, 15, 30, and 60 for serum gh, igf-1, and lanreotide assessment.
Results:
Twenty-four patients were enrolled and all were evaluable. except for the 3 and 6 mg doses, for which the observation of a grade 3 side effect required that an additional three patients be treated, it was sufficient to treat 3 patients at each dose. the overall incidence of side effects was as follows: changes in bowel habits, 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 increase in the incidence, intensity, or duration of side effects was observed 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), intermediate (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%, respectively. serum lanreotide levels declined during treatment in all of the dose 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 group). no antitumor activity or tumor marker reduction was observed.
Conclusions:
No increase in toxicity was observed when subcutaneous lanreotide 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 ensure constant serum drug concentrations over time.