A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate

Justine Yang Bruce, Jens Eickhoff, Roberto Pili, Theodore Logan, Michael Carducci, Jamie Arnott, Anthony Treston, George Wilding, Glenn Liu

Research output: Contribution to journalArticle

45 Citations (Scopus)

Abstract

Background: Current treatment for metastatic renal cell cancer with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) have provided improved overall survival, but complete responses are rare. We conducted a multicenter phase II study to evaluate the objective response rate of 2-methoxyestradiol (2ME2 NCD) alone and in combination with sunitinib for patients with metastatic renal cell carcinoma who have progressed on sunitinib alone. Methods: Adults with metastatic kidney cancer were stratified depending on whether they were still taking sunitinib or had discontinued sunitinib therapy at the time of registration. Patients were treated with 2ME2 NCD alone or in combination with sunitinib. The primary endpoint was objective response rate. Results: In total, 17 patients were enrolled, and 12 were evaluable for response (arm A, n=7; arm b, n=5). In arm A, four patients had the best response of stable disease, and three patients developed disease progression. In arm B, three patients had a best response of stable disease, and two patients had disease progression. One patient continued to receive treatment for a total of 14 cycles before developing disease progression. Fatigue was the most common observed toxicities. Thirty five percent of patients required discontinuation of therapy secondary to toxicities. Conclusions: 2ME2 NCD had minimal anti-tumor activity, with no observed objective responses. The study was terminated because 2ME2 NCD was not found to be tolerable at the recommended phase 2 dose in this patient population. A newer 2ME2 analog is in development with a more favorable toxicity profile and increased potency.

Original languageEnglish
Pages (from-to)794-802
Number of pages9
JournalInvestigational New Drugs
Volume30
Issue number2
DOIs
StatePublished - Apr 2012

Fingerprint

Renal Cell Carcinoma
Nanoparticles
Disease Progression
2-methoxyestradiol
sunitinib
Kidney Neoplasms
Therapeutics
Protein-Tyrosine Kinases
Vascular Endothelial Growth Factor A
Fatigue
Survival

Keywords

  • 2-methoxyestradiol
  • Antiangiogenic agent
  • Clinical trials
  • Phase II
  • Renal cell carcinoma
  • Sunitinib malate

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

A phase II study of 2-methoxyestradiol nanocrystal colloidal dispersion alone and in combination with sunitinib malate in patients with metastatic renal cell carcinoma progressing on sunitinib malate. / Bruce, Justine Yang; Eickhoff, Jens; Pili, Roberto; Logan, Theodore; Carducci, Michael; Arnott, Jamie; Treston, Anthony; Wilding, George; Liu, Glenn.

In: Investigational New Drugs, Vol. 30, No. 2, 04.2012, p. 794-802.

Research output: Contribution to journalArticle

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abstract = "Background: Current treatment for metastatic renal cell cancer with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) have provided improved overall survival, but complete responses are rare. We conducted a multicenter phase II study to evaluate the objective response rate of 2-methoxyestradiol (2ME2 NCD) alone and in combination with sunitinib for patients with metastatic renal cell carcinoma who have progressed on sunitinib alone. Methods: Adults with metastatic kidney cancer were stratified depending on whether they were still taking sunitinib or had discontinued sunitinib therapy at the time of registration. Patients were treated with 2ME2 NCD alone or in combination with sunitinib. The primary endpoint was objective response rate. Results: In total, 17 patients were enrolled, and 12 were evaluable for response (arm A, n=7; arm b, n=5). In arm A, four patients had the best response of stable disease, and three patients developed disease progression. In arm B, three patients had a best response of stable disease, and two patients had disease progression. One patient continued to receive treatment for a total of 14 cycles before developing disease progression. Fatigue was the most common observed toxicities. Thirty five percent of patients required discontinuation of therapy secondary to toxicities. Conclusions: 2ME2 NCD had minimal anti-tumor activity, with no observed objective responses. The study was terminated because 2ME2 NCD was not found to be tolerable at the recommended phase 2 dose in this patient population. A newer 2ME2 analog is in development with a more favorable toxicity profile and increased potency.",
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AU - Logan, Theodore

AU - Carducci, Michael

AU - Arnott, Jamie

AU - Treston, Anthony

AU - Wilding, George

AU - Liu, Glenn

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N2 - Background: Current treatment for metastatic renal cell cancer with vascular endothelial growth factor (VEGF) tyrosine kinase inhibitors (TKI) have provided improved overall survival, but complete responses are rare. We conducted a multicenter phase II study to evaluate the objective response rate of 2-methoxyestradiol (2ME2 NCD) alone and in combination with sunitinib for patients with metastatic renal cell carcinoma who have progressed on sunitinib alone. Methods: Adults with metastatic kidney cancer were stratified depending on whether they were still taking sunitinib or had discontinued sunitinib therapy at the time of registration. Patients were treated with 2ME2 NCD alone or in combination with sunitinib. The primary endpoint was objective response rate. Results: In total, 17 patients were enrolled, and 12 were evaluable for response (arm A, n=7; arm b, n=5). In arm A, four patients had the best response of stable disease, and three patients developed disease progression. In arm B, three patients had a best response of stable disease, and two patients had disease progression. One patient continued to receive treatment for a total of 14 cycles before developing disease progression. Fatigue was the most common observed toxicities. Thirty five percent of patients required discontinuation of therapy secondary to toxicities. Conclusions: 2ME2 NCD had minimal anti-tumor activity, with no observed objective responses. The study was terminated because 2ME2 NCD was not found to be tolerable at the recommended phase 2 dose in this patient population. A newer 2ME2 analog is in development with a more favorable toxicity profile and increased potency.

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