Plasma concentrations and tolerability of a novel
somatostatin analogue
sms-D70 were studied in patients with metastatic
hormone-resistant
prostate cancer (HRPC) or metastatic
renal cell cancer. To overcome the limitations of the octapeptides having affinity only to
somatostatin receptor subtypes 2 and 5, HRPC expressing mainly
somatostatin receptors 1 and 4, a
somatostatin derivative based on the natural
somatostatin having affinity to all five
somatostatin receptor subtypes, was developed. The in vivo stability of this
dextran-conjugated derivative, somatostatin-D70, was confirmed previously in animal studies, and the nanomolar "panaffinity" has been shown in in vitro receptor binding studies on cell lines transfected with the
somatostatin receptor genes.
Sms-D70 was given with
subcutaneous injection once a week at dose levels of 5, 10, 20, 35, and 50 mg. For pharmacokinetic studies,
sms-D70 was labeled with 131I. Fourteen patients were treated, of whom 10 had prostate and 4
renal cell cancer. The kinetic data revealed high stability with a long half-life in the blood. The
drug was well tolerated, and no grade 4 (WHO) toxicity was observed. The maximal tolerated dose could not be established due to the lack of dose-limiting toxicities. Objective PSA responses were not recorded in these heavily treated patients, but subjective stabilization of
pain was observed and urinary symptoms were alleviated in four patients. Three patients with metastatic HRPC received 5-10-mg
intravenous injections of
sms-D70 once weekly for 4-14 months on a compassionate use basis. In all cases, serum PSA values decreased more than 50% from the pretreatment level, but these results are difficult to interpret due to concomitant treatments given to these patients. In conclusion,
sms-D70 was well tolerated in the treatment of metastatic prostate and
renal cell cancer, but no responses were found in these heavily treated patients.