Phase I study combining treatment with temsirolimus and sunitinib malate in patients with advanced renal cell carcinoma

Clin Genitourin Cancer. 2009 Jan;7(1):24-7. doi: 10.3816/CGC.2009.n.004.


Purpose: Concurrent inhibition of multiple oncogenic signaling pathways might improve the efficacy of anticancer agents and abrogate resistance mechanisms. This phase I study evaluated temsirolimus in combination with sunitinib in patients with advanced RCC.

Patients and methods: Eligibility included advanced RCC and <or= 2 previous systemic regimens. At the starting dose, temsirolimus 15 mg was administered by intravenous (I.V.) infusion once weekly, and sunitinib 25 mg was administered orally once daily for 4 weeks, followed by a 2-week rest period.

Results: In the first cohort, dose-limiting toxicities (grade 3 treatment-related toxicities that lasted >or= 7 days) were observed in 2 of 3 patients. One patient experienced grade 3 rash during week 3, which led to treatment discontinuation. A second patient had grade 3 thrombocytopenia (platelet count, 48,000/microL), cellulitis, and gout during week 3 and was hospitalized; platelets recovered to 109,000/microL 4 days after discontinuation of protocol therapy. A third patient experienced rash, asthenia, diarrhea, stomatitis, constipation, fever, and rectal hemorrhage, all of which were mild in severity. The study was terminated because of dose-limiting toxicity observed at low starting doses of both agents.

Conclusion: Concomitant use of I.V. temsirolimus 15 mg weekly and oral sunitinib 25 mg daily (4 weeks on, 2 weeks off) is not recommended.

Publication types

  • Case Reports
  • Clinical Trial, Phase I

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Carcinoma, Renal Cell / drug therapy*
  • Carcinoma, Renal Cell / pathology
  • Cellulitis / chemically induced*
  • Diarrhea / chemically induced
  • Drug Eruptions / etiology*
  • Female
  • Humans
  • Indoles / administration & dosage
  • Indoles / adverse effects
  • Infusions, Intravenous
  • Kidney Neoplasms / drug therapy*
  • Kidney Neoplasms / pathology
  • Male
  • Middle Aged
  • Pyrroles / administration & dosage
  • Pyrroles / adverse effects
  • Sirolimus / administration & dosage
  • Sirolimus / adverse effects
  • Sirolimus / analogs & derivatives
  • Stomatitis / chemically induced*
  • Sunitinib
  • Thrombocytopenia / chemically induced*
  • Treatment Outcome


  • Indoles
  • Pyrroles
  • temsirolimus
  • Sunitinib
  • Sirolimus