A phase II study of everolimus in combination with imatinib for previously treated advanced renal carcinoma

Invest New Drugs. 2011 Apr;29(2):374-9. doi: 10.1007/s10637-009-9365-y. Epub 2009 Dec 10.

Abstract

Purpose: This phase II study evaluated the activity of combined treatment with the mTOR inhibitor everolimus and the PDGFR inhibitor imatinib in patients with previously-treated, advanced renal carcinoma. The primary endpoint was estimation of the 3-month progression-free rate.

Patients and methods: Eligible patients had metastatic or unresectable clear cell renal carcinoma, at least one prior systemic therapy, no prior mTOR inhibitor therapy, performance status 0-2, and measurable disease. Treatment consisted of everolimus 2.5 mg p.o. daily and imatinib 600 mg p.o. daily. The primary endpoint was the 3-month progression-free rate.

Results: The study was closed after the first 19 patients because of an insufficient number of patients who were progression-free at 3 months. The 3-month progression-free rate was 49% (95% C.I. 23%, 72%) and the median progression-free survival was 2.9 months (95% C.I. 1.9, 6.2). Toxicities with an incidence of > 50% included nausea, elevated serum creatinine, edema, anemia, hypocalcemia, fatigue, diarrhea, vomiting, and dyspnea, and leukopenia.

Conclusion: The combination of everolimus with imatinib in previously treated patients with advanced renal carcinoma did not result in a sufficient 3-month progression-free rate to warrant further investigation of this combination.

Publication types

  • Clinical Trial, Phase II
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Antineoplastic Agents / administration & dosage
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Benzamides
  • Everolimus
  • Female
  • Humans
  • Imatinib Mesylate
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Piperazines / administration & dosage
  • Piperazines / adverse effects
  • Piperazines / therapeutic use*
  • Pyrimidines / administration & dosage
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Sirolimus / administration & dosage
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives*
  • Sirolimus / therapeutic use
  • Survival Analysis
  • Treatment Outcome

Substances

  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Everolimus
  • Sirolimus