Efficacy of Temsirolimus after Previous Treatment with Sunitinib, Sorafenib or Everolimus in Advanced Renal Cell Cancer

Abstract

Objective: Temsirolimus inhibits the mammalian target of rapamycin with demonstrated efficacy in patients with advanced renal cell cancer. Patients and Methods: We present a retrospective analysis of our single-center experience with temsirolimus in patients pretreated with sunitinib, sorafenib or everolimus. Sixteen patients were treated within our center starting in December 2006 until September 2009. The majority of patients (14 of 16) had received a prior antiangiogenic pretreatment. We further analyzed the efficacy of subsequent treatment with temsirolimus in these patients. Results: Stable disease could be achieved in 8 of 14 pretreated patients (57%). The duration of median progression-free survival was 10 weeks (range 1–43). Especially patients with a good response to previous antiangiogenic treatment, a good overall condition and a low Memorial Sloan Kettering Cancer Center (MSKCC) score benefited from subsequent treatment with temsirolimus. We did not see any complete or partial response meeting the World Health Organization criteria. Temsirolimus was well tolerated. Conclusion: Temsirolimus appears to be an effective and well-tolerated substance in the treatment of patients with a good performance status, low MSKCC score and stable disease under previous antiangiogenic treatment in advanced renal cell cancer. However, its use is highly questionable in pretreated patients with a poor performance score and a high MSKCC score.

A phase II study of alternating sunitinib and temsirolimus therapy in patients with metastatic renal cell carcinoma

“…Treatment-emergent AEs experienced by >10% of patients are detailed in Table 4. The most common treatment-emergent AEs were (n of total observed): fatigue (17), platelet count decreased (12), creatinine increased (12), diarrhea (10), oral mucositis (10), limb edema (9), anemia (8), rash (8), hypophosphatemia (7), dysgeusia (7), and palmar-plantar erythrodysesthesia syndrome (7). A greater total number of AEs were related to sunitinib (117) than temsirolimus (65).…”

“…However, this combination was poorly tolerated due to observed dose‐limiting toxicities (DLTs) which included mucositis, neutropenia, anemia, thrombocytopenia, rash, and cellulitis 7,8 . Retrospective studies and a subsequent Phase III trial indicated that temsirolimus treatment following sunitinib was tolerable and provided feasibility for such a sequential therapy regimen in mRCC 9–12 . The concept of sequential or alternating therapy is not new, 13–15 and alternating drugs that have different molecular targets and affect independent signaling pathways after each cycle minimize the likelihood of the development of multi‐resistant cancer cells 16 .…”

“… 7 , 8 Retrospective studies and a subsequent Phase III trial indicated that temsirolimus treatment following sunitinib was tolerable and provided feasibility for such a sequential therapy regimen in mRCC. 9 , 10 , 11 , 12 The concept of sequential or alternating therapy is not new, 13 , 14 , 15 and alternating drugs that have different molecular targets and affect independent signaling pathways after each cycle minimize the likelihood of the development of multi‐resistant cancer cells. 16 Dos Santos et al treated with alternating sunitinib and everolimus (mTOR inhibitor) every 1, 2, or 3 weeks in a human Caki‐1 RCC xenograft mouse model.…”