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Torisel (Temsirolimus) - Summary

 
 



TORISEL SUMMARY

Temsirolimus, an inhibitor of mTOR, is an antineoplastic agent.

TORISEL is indicated for the treatment of advanced renal cell carcinoma.


See all Torisel indications & dosage >>

NEWS HIGHLIGHTS

Media Articles Related to Torisel (Temsirolimus)

Clinical Focus in Renal Cell Carcinoma: Indolent Disease Tx
Source: MedPage Today Oncology/Hematology [2014.11.19]
(MedPage Today) -- Initial observation and intermittent therapy might be options for selected patients.

Clinical Focus In Renal Cell Carcinoma: Clues from Gene Studies
Source: MedPage Today Oncology/Hematology [2014.11.17]
(MedPage Today) -- Mutations in four genes appear to play a key role in the origin of renal cell carcinoma.

more news >>

Published Studies Related to Torisel (Temsirolimus)

Temsirolimus and bevacizumab, or sunitinib, or interferon alfa and bevacizumab for patients with advanced renal cell carcinoma (TORAVA): a randomised phase 2 trial. [2011.07]
BACKGROUND: Combining targeted treatments for renal cell carcinoma has been suggested as a possible method to improve treatment efficacy. We aimed to assess the potential synergistic or additive effect of the combination of bevacizumab, directed against the VEGF receptor, and temsirolimus, an mTOR inhibitor, in metastatic renal cell carcinoma... INTERPRETATION: The toxicity of the temsirolimus and bevacizumab combination was much higher than anticipated and limited treatment continuation over time. Clinical activity was low compared with the benefit expected from sequential use of each targeted therapy. This combination cannot be recommended for first-line treatment in patients with metastatic renal cell carcinoma. FUNDING: French Ministry of Health and Wyeth Pharmaceuticals. Copyright (c) 2011 Elsevier Ltd. All rights reserved.

Quality of life in patients with advanced renal cell carcinoma treated with temsirolimus or interferon-alpha. [2010.05.11]
BACKGROUND: Temsirolimus was approved in Europe as first-line treatment of poor-prognosis advanced renal cell carcinoma (advRCC) based on significant clinical benefits... CONCLUSION: Temsirolimus is associated with significantly higher EQ-5D scores compared with interferon-alpha in patients with previously untreated poor-prognosis advRCC.

Cost-effectiveness of sorafenib for second-line treatment of advanced renal cell carcinoma. [2010.01]
OBJECTIVES: To estimate the cost-effectiveness of sorafenib (Nexavar, Bayer, Leverkusen, Germany) versus best supportive care (BSC) for second-line treatment of advanced renal cell carcinoma from the perspective of the UK National Health Service... CONCLUSIONS: Sorafenib has been shown to be clinically effective compared to BSC, offering additional health benefits; however, with a cost per QALY in excess of pound70,000, it may not be regarded as a cost-effective use of resources in some health-care settings.

FDA approval summary: temsirolimus as treatment for advanced renal cell carcinoma. [2010]
This report summarizes the U.S... Temsirolimus has demonstrated superiority in terms of OS and PFS over IFN-alpha and provides an additional treatment option for patients with advanced RCC.

Q-TWiST analysis of patients receiving temsirolimus or interferon alpha for treatment of advanced renal cell carcinoma. [2010]
BACKGROUND AND OBJECTIVES: For patients with advanced cancers, it is important that treatment improves the quality as well as the quantity of survival. This quality-adjusted time without symptoms of progression or toxicity (Q-TWiST) analysis provides a combined measure of both the overall survival interval and the quality of survival for patients with advanced renal cell carcinoma (RCC) receiving temsirolimus, interferon (IFN)-alpha or the combination of these agents, using data from a phase III clinical trial... CONCLUSION: Temsirolimus resulted in significantly longer Q-TWiST (quality-adjusted survival) in patients with advanced RCC than IFNalpha therapy.

more studies >>

Clinical Trials Related to Torisel (Temsirolimus)

IMC-A12 in Combination With Temsirolimus (CCI-779) in Patients With Advanced Cancers [Recruiting]
The goal of this clinical research study is to find the highest tolerable dose combination of IMC-A12 and temsirolimus that can be given to patients with advanced or metastatic cancer. Researchers will look at safety of the study drugs, and whether the study dosing schedule is tolerated by participants. Researchers will also perform biomarker tests to study how IMC-A12 and temsirolimus affect genes (material in the cells passed from parent to child that gives the child certain traits or characteristics) or proteins (the building blocks of cells) found in the blood.

Temsirolimus and Radiation for Non-Small Cell Lung Cancer [Recruiting]
To determine the maximum tolerated dose of the drug temsirolimus (15mg, 20mg or 25mg) given with radiation therapy for patients with non-small cell lung cancer.

Temsirolimus (CCI-770, Torisel) Combined With Cetuximab in Cetuximab-Refractory Colorectal Cancer [Recruiting]
In this study, the investigational drug, temsirolimus, will be combined with cetuximab, a biologic agent used in the treatment of colorectal cancer. Cetuximab in combination with temsirolimus may be more effective in treating advanced colorectal cancer than cetuximab alone. The purpose of this research study is to try to define the highest dose of cetuximab that can be used safely in combination with temsirolimus to treat advanced colorectal cancer that has progressed through standard therapy.

Phase I Study of Docetaxel and Temsirolimus in Resistant Solid Malignancies [Recruiting]
Rationale:

The Mammalian Target of Rapamycin (mTOR) is a large polypeptide serine/threonine kinase of 289 kDa; kinases have been shown to be important regulators of cancer cell cycle, proliferation, invasion, and angiogenesis, and mTOR has been shown to have a key role in the signaling of malignant cell growth, proliferation, differentiation, migration, and survival. Inhibition of mTOR would result in arrest of cell growth in the G1 phase of the cell cycle.

Temsirolimus (CCI-779) is a soluble ester analogue of rapamycin (sirolimus) which has shown impressive in vitro and in vivo cytostatic activity in selectively inhibiting mTOR. In animal models, temsirolimus has demonstrated an impressive cytostatic effect on a wide variety of cancer cells. In vitro, it inhibited the growth of human T-cell leukemia, glioblastoma, melanoma, prostate, breast, renal cell, and pancreatic cells, all of which showed particular sensitivity to temsirolimus, with significant growth inhibition at concentrations of less that 0. 01micrometers. In Phase I trials, temsirolimus has been investigated as a single agent on a weekly schedule as well as daily for 5 days every other

week, and evidence of activity was observed over the entire dose range (15 - 220 mg/m2) in

patients with both breast and renal cancer. There was no apparent relationship between exposure and clinical benefit, suggesting that the inhibition of mTOR may be achieved at doses well below dose levels that result in dose limiting toxicities. Major tumor responses were noted in Phase I trials in patients previously treated with lung, breast, renal as well as neuroendocrine tumors. Minor responses were noted in soft tissue sarcoma, endometrial, and cervical carcinoma.

Docetaxel is a taxane analog which is active against many solid tumors including breast, non-small cell lung, prostate, gastric, ovarian, head and neck, and pancreatic cancers, soft tissue sarcoma, and melanoma. It has been shown in several Phase III studies to have clinically significant activity in several solid tumors.

We propose treating patients with resistant solid malignancies with docetaxel and temsirolimus. In a study using human breast cancer cell lines, mTOR inhibition with rapamycin had a synergistic cytotoxic effect with paclitaxel. Given the novel mechanism of action of mTOR inhibitors and known synergistic activity of an mTOR inhibitor, rapamycin, with a taxane, paclitaxel, in vitro, we envision that this regimen would be highly active in patients with solid tumor malignancies.

Objectives:

Primary

- To define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of

temsirolimus in combination with pegylated liposomal doxorubicin in patients with resistant solid malignancies.

- To determine the incidence and severity of other toxicities of temsirolimus in

combination with pegylated liposomal doxorubicin in patients with resistant solid malignancies.

Secondary

- To assess the pharmacokinetic profile of temsirolimus in combination with pegylated

liposomal doxorubicin.

- To determine any anti-tumor activity and response to the combination of temsirolimus

and pegylated liposomal doxorubicin in treatment of patients with resistant solid malignancies.

Phase I Study of DOXIL and Temsirolimus in Resistant Solid Malignancies [Recruiting]
Rationale:

The Mammalian Target of Rapamycin (mTOR) is a large polypeptide serine/threonine kinase of 289 kDa; kinases have been shown to be important regulators of cancer cell cycle, proliferation, invasion, and angiogenesis, and mTOR has been shown to have a key role in the signaling of malignant cell growth, proliferation, differentiation, migration, and survival. Inhibition of mTOR would result in arrest of cell growth in the G1 phase of the cell cycle.

Temsirolimus (CCI-779) is a soluble ester analogue of rapamycin (sirolimus) which has shown impressive in vitro and in vivo cytostatic activity in selectively inhibiting mTOR. In animal models, temsirolimus has demonstrated an impressive cytostatic effect on a wide variety of cancer cells. In vitro, it inhibited the growth of human T-cell leukemia, glioblastoma, melanoma, prostate, breast, renal cell, and pancreatic cells, all of which showed particular sensitivity to temsirolimus, with significant growth inhibition at concentrations of less that 0. 01micrometer. In Phase I trials, temsirolimus has been investigated as a single agent on a weekly schedule as well as daily for 5 days every other

week, and evidence of activity was observed over the entire dose range (15 - 220 mg/m2) in

patients with both breast and renal cancer. There was no apparent relationship between exposure and clinical benefit, suggesting that the inhibition of mTOR may be achieved at doses well below dose levels that result in dose limiting toxicities. Major tumor responses were noted in Phase I trials in patients previously treated with lung, breast, renal as well as neuroendocrine tumors. Minor responses were noted in soft tissue sarcoma, endometrial, and cervical carcinoma.

Pegylated liposomal doxorubicin has been FDA approved for use in refractory metastatic ovarian cancer and AIDS-related Kaposi's Sarcoma. It has also been shown to be effective in previously treated metastatic breast cancer.

Combination studies in preclinical models suggest that rapamycin and its analogues are at least additive in effect with standard chemotherapy and radiation. In addition, studies in breast cancer cell lines suggest that the mTOR inhibitors may reverse resistance to anti-estrogen agents. Thus, we are proposing that the combination of temsirolimus and liposomal doxorubicin will be highly effective in metastatic solid tumor malignancies.

Objectives:

Primary

- To define the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT) of

temsirolimus in combination with pegylated liposomal doxorubicin in patients with resistant solid malignancies.

- To determine the incidence and severity of other toxicities of temsirolimus in

combination with pegylated liposomal doxorubicin in patients with resistant solid malignancies.

Secondary

- To assess the pharmacokinetic profile of temsirolimus in combination with pegylated

liposomal doxorubicin.

- To determine any anti-tumor activity and response to the combination of temsirolimus

and pegylated liposomal doxorubicin in treatment of patients with resistant solid malignancies.

more trials >>

Reports of Suspected Torisel (Temsirolimus) Side Effects

Disease Progression (39)Death (25)Renal Cell Carcinoma (19)Dyspnoea (15)Decreased Appetite (14)Fatigue (12)Rash (12)Diarrhoea (12)Nausea (9)Neoplasm Malignant (9)more >>


Page last updated: 2014-11-19

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