HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Phase I trial on sms-D70 somatostatin analogue in advanced prostate and renal cell cancer.

Abstract
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.
AuthorsT K Joensuu, S Nilsson, A R Holmberg, M Márquez, M Tenhunen, T Saarto, H Joensuu
JournalAnnals of the New York Academy of Sciences (Ann N Y Acad Sci) Vol. 1028 Pg. 361-74 (Dec 2004) ISSN: 0077-8923 [Print] United States
PMID15650261 (Publication Type: Clinical Trial, Clinical Trial, Phase I, Journal Article)
Chemical References
  • Antineoplastic Agents
  • Receptors, Somatostatin
  • sms-D70
  • Somatostatin
  • Prostate-Specific Antigen
Topics
  • Adult
  • Aged
  • Antineoplastic Agents (therapeutic use)
  • Carcinoma, Renal Cell (drug therapy)
  • Disease Progression
  • Female
  • Humans
  • Kidney Neoplasms (drug therapy)
  • Kinetics
  • Male
  • Maximum Tolerated Dose
  • Middle Aged
  • Neoplasm Metastasis
  • Prostate-Specific Antigen (chemistry)
  • Prostatic Neoplasms (drug therapy)
  • Protein Binding
  • Receptors, Somatostatin (metabolism)
  • Somatostatin (analogs & derivatives, therapeutic use)
  • Time Factors

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: