Treatment for Metastatic Kidney Cancer - Temsirolimus

Kidney Cancer Treatment Options at The Kidney Cancer Institute

Metastatic Kidney Cancer
Written by Jaime Landman, Jamie Kearns and George Haramis

Temsirolimus
(ToriselT, Wyeth, Inc.- Year approved: 2007)

Temsirolimus is also known as Torisel. Temsirolimus is a specific inhibitor of mTOR and interferes with the creation of proteins that regulate proliferation, growth and survival of kidney cancer cells. Temsirolimus also inhibits tumor angiogenesis by reducing the synthesis of VEGF. Temsirolimus is administered intravenously at an approved dose of 25mg every week.

An international phase III study performed in 2007 investigated Temsirolimus as first-line therapy for patients with advanced kidney cancer with poor risk factors and metastases. The study randomized 626 patients to receive Temsirolimus, interferon-? or the combination of these two drugs. The results were published in the New England Journal of Medicine in 2007 and were very promising for this particular group of patients. Compared to interferon-a, Temsirolimus by itself was associated with an increase in overall survival (10.9 months vs. 7.3 months), progression-free survival (5.5 months vs. 3.1 months), and response rate (8.6% vs. 4.8%) and was better tolerated than Interferon-? alone (grades 3–4 adverse effects: 69% vs. 85%). The combination of Temsirolimus and Interferon-? did not add benefit over treatment with Temsirolimus alone in overall survival, and patients who received the combination of both Temsirolimus and Interferon-? experienced an increase in severe adverse events (grades 3–4 adverse effects: 87%). This pivotal study was the first to show an overall survival advantage with single-agent Temsirolimus compared with interferon-? in patients with previously untreated advanced kidney cancer.

The above image demonstrates relative progression-free survival (survival with the kidney cancer disease totally stable) of patients with metastatic kidney cancer taking Sutent vs. interferon alpha. The separation of the curves from 1 to 11 months demonstrates that patients who received Sutent had a longer period on average without progression of their metastatic kidney cancer than patients who received interferon alpha. Importantly, the lines come together again between 11 and 12 months, demonstrating that Sutent can increase the amount of time patients will live with metastatic kidney cancer before it gets worse. The differences noted in this study are probably even more pronounced than the results appear as patients who were not doing well on the interferon treatment were switched over to Sunitinib. Results of this study proved the superiority of Sunitinib over IFN-a as first-line treatment for patients with metastatic conventional kidney cancer.

Adverse Effects:
Treatment with Temsirolimus has been generally well tolerated in clinical settings by patients with advanced RCC. Temsirolimus is associated with mild to moderate rash (skin reaction) but not with hand/foot skin reactions, which can occur in patients treated with Sunitinib and Sorafenib. Grade 3 or 4 adverse events were experienced by 67% of patients in the Temsirolimus arm versus 87% of patients in the interferon-? arm. Allergic or hypersensitivity reactions occurred in 9% of patients. Rare serious adverse reactions associated with Temsirolimus, included interstitial lung disease, bowel perforation, and acute renal failure.

Adverse Reactions to IV Temsirolimus
Adverse Effects	All Grades	Grade 3 or (%)
Fatigue	51	11
Rash	47	5
Mucositis or Stomatitis	41	3
Nausea	37	2
Edema	35	3
Anorexia	32	3
Dyspnea	28	9
Pain	28	5
Diarrhea	27	1
Cough	26	1
Pyrexia	24	1
Abdominal pain	21	4
Infections	20	3
Constipation	20	-
Back pain	20	3
Dysgeusia	20	-
Labaratory Abnormalities
Hemoglobin decreased	94	20
Platelets decreased	40	1
Triglycerides increased	83	44
Glucose increased	89	16
Total cholesterol increased	87	2
Alkaline phosphate increased	68	3
Alkaline phosphate increased	57	3