Temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR) kinase, is an antineoplastic agent.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12
Temsirolimus is used for the treatment of advanced renal cell carcinoma (RCC)1, 2, 12 and is designated an orphan drug by FDA for this use.17
The current indication for temsirolimus is based principally on the results of a randomized, open-label, multicenter phase 3 study in 626 patients with previously untreated, poor-prognosis, advanced renal cell carcinoma.1, 2 In this study, patients were randomized to receive temsirolimus (25 mg IV weekly), interferon alfa (3 million units subcutaneously 3 times weekly, increased up to 18 million units if tolerated), or combination therapy with temsirolimus (15 mg IV weekly) and interferon alfa (3 million units, increased to 6 million units, subcutaneously 3 times weekly).1, 2 Approximately 80% of patients had clear-cell carcinoma histology,2 67% had undergone nephrectomy,1, 2 and approximately 80% had been diagnosed as having metastatic disease within 12 months prior to study entry.2, 20 Median overall survival was prolonged in patients receiving temsirolimus alone (10.9 months) compared with those receiving interferon alfa alone (7.3 months); however, the combination of temsirolimus and interferon alfa did not significantly improve overall survival (8.4 months) when compared with interferon alfa alone.1, 2 Median progression-free survival times, as determined by radiologic assessments performed at 8-week intervals, were 5.5, 3.1, or 4.7 months in patients receiving temsirolimus alone, interferon alfa alone, or the combination regimen, respectively.1, 2, 20
Clear-cell histology is the most common subtype of renal cell carcinoma (RCC); guidelines published by the American Society of Clinical Oncology (ASCO) in 2022 provide recommendations for the management of metastatic clear-cell RCC.23 In patients with newly-diagnosed metastatic clear-cell RCC who require systemic treatment, dual combined immune checkpoint inhibitor therapy, an immune checkpoint inhibitor in combination with a vascular endothelial growth factor (VEGFR) tyrosine kinase inhibitor, or monotherapy with an agent from either class are generally recommended according to disease risk stratification and comorbidities.23 In the second- and subsequent-line setting, treatment with nivolumab or cabozantinib is recommended in patients who experienced disease progression with VEGFR tyrosine kinase inhibitor monotherapy.23 Temsirolimus is not included in the treatment recommendations for first-, second-, or later-line treatment of clear cell renal cell carcinoma.23
The National Cancer Institute (NCI) includes temsirolimus as one of several treatment options for first-line therapy of stage IV renal cancer.22 Use of temsirolimus in immediate and poor risk patients has been shown to result in prolonged outcome survival compared with interferon alfa.2, 22
Dispensing and Administration Precautions
Temsirolimus is administered by IV infusion.1 The manufacturer recommends use of an infusion pump to ensure accurate drug delivery.1
The commercially available injection must be diluted with the supplied diluent and then further diluted with 0.9% sodium chloride injection.1
Temsirolimus injection concentrate contains polysorbate 80, which can cause leaching of diethylhexylphthalate (DEHP) from polyvinyl chloride (PVC) infusion bags and administration sets.1 To minimize exposure of patients to leached DEHP, appropriate administration materials should be composed of glass, polyolefin, or polyethylene.1 An in-line polyethersulfone filter with a pore size not exceeding 5 µm should be used.1
Temsirolimus injection concentrate should be protected from light, stored at 2-8°C, and protected from excessive room light and sunlight during handling and preparation.1, 6
To avoid precipitation, temsirolimus injection concentrate must be diluted in a 2-step process prior to administration. 1
In the first dilution step, 1.8 mL of the nonaqueous diluent provided should be added to a vial labeled as containing 25 mg/mL of temsirolimus; the resultant solution contains approximately 10 mg/mL of the drug in a total volume of 3 mL.1 Contents of the vial should be mixed well by inversion, allowing sufficient time for air bubbles to subside.1 Temsirolimus solutions that have been diluted to 10 mg/mL (initial dilution) may be stored for up to 24 hours at controlled room temperature (<25°C).1
In the second dilution step, the appropriate dose of temsirolimus should be withdrawn from the vial, then rapidly diluted in 250 mL of 0.9% sodium chloride injection in a suitable container (polypropylene, polyolefin, polyethylene, or glass).1 The final diluted solution should be mixed by gently inverting the bag or bottle; shaking the container should be avoided to prevent excessive foaming of the solution.1
Precipitation will occur if undiluted temsirolimus injection concentrate is added directly to an aqueous infusion solution (e.g., 0.9% sodium chloride injection).1 Always combine the commercially available injection concentrate with the manufacturer-supplied diluent before adding to infusion solutions.1
Administration of the final diluted solution of temsirolimus should be completed within 6 hours of the time that the diluted temsirolimus mixture is added to the sodium chloride injection.1
Final diluted temsirolimus solutions should be infused IV over 30-60 minutes.1
The recommended adult dosage of temsirolimus in the treatment of advanced renal cell carcinoma is 25 mg by IV infusion once weekly.1 Therapy should be continued until disease progression or unacceptable toxicity occurs.1, 2
Dosage Modification for Toxicity
Therapy should be temporarily interrupted if hematologic toxicities (e.g., absolute neutrophil count less than 1000/mm3, platelet count less than 75,000/mm3) or National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) grade 3 or greater toxicity occurs.1
Following resolution of toxicity to grade 2 or less, temsirolimus may be restarted at a reduced weekly dosage that is 5 mg less than the previous dosage, but not less than 15 mg weekly.1
Dosage Modification for Concomitant Use with Strong CYP3A4 Inhibitors or Inducers
Concomitant use of temsirolimus with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole, grapefruit juice) should be avoided.1 If patients must be administered a strong CYP3A4 inhibitor, consider a dosage reduction of temsirolimus to 12.5 mg weekly.1 If the strong CYP3A4 inhibitor is discontinued, allow a washout period of approximately 1 week before temsirolimus is adjusted back to the dosage used prior to initiation of the CYP3A4 inhibitor.1
Concomitant use with strong CYP3A4 inducers (e.g., dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifampicin, phenobarbital) should be avoided.1 If patients must be administered a strong CYP3A4 inducer, consider a dosage increase of temsirolimus from 25 mg weekly to 50 mg weekly.1 If the strong inducer is discontinued, adjust temsirolimus dosage back to the dosage used prior to initiation of the strong CYP3A4 inducer.1
In patients with mild hepatic impairment (bilirubin >1-1.5 times upper limit of normal [ULN] or AST>ULN but bilirubin ≤ULN), reduce the dosage of temsirolimus to 15 mg weekly.1 Temsirolimus is contraindicated in patients with bilirubin >1.5 times ULN.1
No dosage adjustment is recommended in patients with renal impairment.1
The manufacturer makes no specific geriatric dosage recommendations at this time.1
Hypersensitivity/Infusion Reactions
Hypersensitivity or infusion reactions including, but not limited to, anaphylaxis, dyspnea, flushing, hypotension, apnea, loss of consciousness, and chest pain have been reported.1 These reactions can occur early with the first infusion or with subsequent infusions.1
Temsirolimus should be used with caution in patients with known hypersensitivity to the drug or its metabolites (e.g., sirolimus), polysorbate 80, or any other ingredient in the formulation.1
Pretreatment with an H1 antihistamine prior to each dose of temsirolimus is recommended to prevent hypersensitivity reactions.1, 2, 6 Temsirolimus should be used with caution in patients with known hypersensitivity to antihistamines or with conditions requiring avoidance of antihistamines.1
If a hypersensitivity reaction develops, the infusion should be discontinued and the patient observed for at least 30-60 minutes.1 Treatment may be resumed at the discretion of the physician with administration of a histamine H1-receptor antagonist (e.g., diphenhydramine), if not previously used, and/or with a histamine H2-receptor antagonist (e.g., famotidine 20 mg, ranitidine 50 mg) administered IV approximately 30 minutes before restarting the temsirolimus infusion.1 IV infusion may be resumed at a slower rate (infusion time of up to 60 minutes).1 Assess the risks versus benefits of therapy prior to continuing temsirolinus in patients with severe or life-threatening reactions.1
Hyperglycemia/Glucose Intolerance
Hyperglycemia is likely to develop with the use of temsirolimus.1 Patients may require initiation or increased dosage of insulin and/or an oral hypoglycemic agent.1 Serum glucose should be monitored prior to and during therapy, and patients should be advised to report excessive thirst or any increase in the volume or frequency of urination.1
Immunosuppression may occur with the use of temsirolimus.1 Patients should be carefully observed for infections, including opportunistic infections.1 Pneumocystis jiroveci pneumonia (PJP), including fatalities, reported and may be associated with the concomitant use of corticosteroids or other immunosuppressive agents.1 Consider prophylaxis for PJP when concomitant use of corticosteroids or other immunosuppressive agents is required during temsirolimus treatment.1
Interstitial lung disease, sometimes fatal, has occurred in patients treated with temsirolimus.1 While some patients were asymptomatic or had minimal symptoms with inflitrates on CT scan or chest radiograph, other patients presented with symptoms such as dyspnea, cough, hypoxia, and fever.1
Patients should be observed for signs and symptoms (e.g., dyspnea, cough, hypoxia, fever) and radiographic changes.1 Baseline radiographic assessment by lung CT scan or chest radiograph is recommended prior to initiation of temsirolimus and periodically.1 If clinically significant respiratory symptoms develop, consider withholding temsirolimus until recovery of symptoms and improvement of radiographic findings related to pneumonitis.1 Consideration should be given to use of corticosteroids and/or antibiotics.1
Hyperlipemia with increased triglycerides and cholesterol is likely to develop with the use of temsirolimus.1 Initiation or increased dosage of a lipid-lowering agent may be required.1 Serum cholesterol and triglycerides should be monitored prior to and during therapy.1
Bowel perforations, sometimes fatal, have been reported in patients receiving temsirolimus.1 Patients with metabolic acidosis, fever, abdominal pain, bloody stools, diarrhea, and/or acute abdomen should be promptly evaluated.1
Acute renal failure that is rapidly progressive and sometimes fatal has occurred in patients receiving temsirolimus; these cases were not clearly related to disease progression.1 Renal function should be monitored prior to and during therapy.1 Some patients do not respond to dialysis.1
Abnormal wound healing has been reported with the use of temsirolimus.1 The drug should be used with caution in patients during the perioperative period.1
An increased risk of intracerebral bleeding, sometimes fatal, has been reported in patients with primary CNS tumors or metastases and/or in those receiving anticoagulation therapy while receiving temsirolimus.1
Proteinuria and Nephrotic Syndrome
Proteinura, including nephrotic syndrome, has been reported in patients receiving temsirolimus.1 Monitor urine protein prior to initiation of treatment with temsirolimus and periodically thereafter.1 Discontinue temsirolimus if patients develop nephrotic syndrome.1
Patients should avoid concomitant use of temsirolimus with strong inhibitors or inducers of cytochrome P-450 (CYP) isoenzyme 3A; if alternative treatment cannot be given, adjustment of temsirolimus dosage is recommended.1
Concomitant use of temsirolimus and sunitinib has resulted in dose-limiting toxicity.1
Immunizations and Risks Associated with Live Vaccines
Avoid use of live vaccines and close contact with those who have received live vaccines during treatment with temsirolimus.1 Examples of live vaccines include intranasal influenza, measles, mumps, rubella, oral polio, BCG, yellow fever, varicella, and TY21a typhoid vaccines.1
Fetal/Neonatal Morbidity and Mortality
Temsirolimus may cause fetal harm based on animal findings and mechanism of action.1 Animal studies indicate adverse effects on embryofetal development.1 Advise pregnant women and females of reproductive potential of the potential risk to fetus and of the need to use effective contraception.1 (See Females and Males of Reproductive Potential under Cautions.)
Older adults are more likely to experience certain adverse reactions with temsirolimus (e.g., diarrhea, edema, pneumonia).1
Temsirolimus may cause fetal harm.1 Animal studies indicate adverse effects on embryofetal development.1 Advise pregnant women and females of reproductive potential of the potential risk to the fetus.1
Not known whether temsirolimus is distributed into milk or the effects on the breastfed child or milk production.1 Advise lactating females not to breastfeed during treatment with temsirolimus and for 3 weeks after the final dose.1
Females and Males of Reproductive Potential
Temsirolimus can cause fetal harm when administered to pregnant females.1 Females of reproductive potential should use effective contraception during and for 3 months after completion of temsirolimus treatment.1 Male patients with partners of childbearing potential also should use reliable contraception during temsirolimus treatment and for 3 months after the last dose.1
Based on animal studies, male and female fertility may be compromised by temsirolimus treatment.1 It is not known if the results are reversible.1
There is limited information on the use of temsirolimus in pediatric patients.1 Effectiveness of the drug in pediatric patients with advanced recurrent/refractory solid tumors has not been established.1 In a clinical study that included 59 pediatric patients ages 1-17 years of age, temsirolimus 10 mg/m2 to 150 mg/m2 was given in 3 week cycles for treatment of advanced recurrent/refractory solid tumors to explore safety and pharmacodynamics.1 In a later study, 52 pediatric patients with recurrent/relapsed neruoblastoma, rhabdomyosarcoma, or high grade glioma received temsirolimus 75 mg/m2 weekly.1 One patient with neuroblastoma had a partial response; no objective responses were observed with the other indications for use.1
Adverse reactions associated with temsirolimus in the pediatric population were similar to adults.1 The most common reactions (≥20%) in pediatric patients receiving the temsirolimus 75 mg/m2 weekly dosage included thrombocytopenia, infections, asthenia/fatigue, fever, pain, leukopenia, rash, anemia, hyperlipidemia, increased cough, stomatitis, anorexia, increased plasma levels of alanine aminotransferase and aspartate aminotransferase, hypercholesterolemia, hyperglycemia, abdominal pain, headache, arthralgia, upper respiratory infection, nausea and vomiting, neutropenia, hypokalemia, and hypophosphatemia.1
There is insufficient experience in patients 65 years of age or older to determine whether geriatric patients respond differently than younger adults.1 Elderly patients may be more likely to experience adverse reactions of temsirolimus such as diarrhea, edema, and pneumonia.1
Increased risk of toxicity has been observed in patients with baseline bilirubin >1.5 times the upper limit of normal (ULN) receiving temsirolimus.1 The overall frequency of grade ≥3 adverse reactions and deaths, including deaths due to progression of disease, was greater in such patients compared with those with baseline bilirubin ≤1.5 times ULN.1
If temsirolimus must be used in patients with mild hepatic impairment (bilirubin >1-1.5 times ULN or AST >ULN but bilirubin ≤ULN), reduce the dosage to 15 mg weekly.1 Assess AST and bilirubin levels before initiation of temsirolimus therapy and periodically thereafter to manage dosage adjustments.1
Temsirolimus is contraindicated in patients with bilirubin >1.5 times ULN.1
Safety and efficacy of temsirolimus in patients with renal impairment have not been studied specifically to date.1 Renal impairment is not expected to substantially alter systemic exposure to the drug.1
The most common adverse reactions (≥30%) reported with temsirolimus are rash, asthenia, mucositis, nausea, edema, and anorexia.1 The most common laboratory abnormalities (≥30%) are anemia, hyperglycemia, hyperlipidemia, hypertriglyceridemia, elevated alkaline phosphatase, elevated serum creatinine, lymphopenia, hypophosphatemia, thrombocytopenia, elevated AST, and leukopenia.1
Both temsirolimus and its principal active metabolite, sirolimus, are metabolized by cytochrome P-450 (CYP) isoenzyme 3A4.1, 6, 16, 18 In vitro studies using human liver microsomes indicate that temsirolimus inhibits CYP isoenzymes 2D6 and 3A4.1
Drugs Affecting Hepatic Microsomal Enzymes
CYP3A4 inhibitors: Potential pharmacokinetic interaction (increased plasma concentrations of the principal active metabolite sirolimus).1 Concomitant use with a potent CYP3A4 inhibitors should be avoided; if no alternative is available, consideration should be given to temsirolimus dosage adjustment.1
CYP3A4 inducers: Potential pharmacokinetic interaction (decreased plasma concentrations of the principal active metabolite sirolimus).1 Concomitant use with potent CYP3A4 inducers should be avoided; if no alternative is available, consideration should be given to temsirolimus dosage adjustment.1
For specific recommendations when temsirolimus is used concomitantly with a potent inhibitor or inducer of CYP3A4, see the following sections on interactions with specific drugs or drug classes.
Drugs Metabolized by Hepatic Microsomal Enzymes
Substrates of CYP2D6 and CYP3A: No evidence of clinically important effects in drug interaction studies with substrates of CYP2D6; no effect is anticipated when temsirolimus is co-administered with drugs metabolized by CYP3A or CYP2D6.1
Drugs Affecting or Affected by Transport Systems
Temsirolimus is a substrate of P-glycoprotein (P-gp) in vitro.1 If temsirolimus is administered with drugs that inhibit P-gp, increased concentrations of temsirolimus are likely and caution should be exercised.1
In vitro, temsirolimus inhibited P-gp.1 If temsirolimus is administered with drugs that are substrates of P-gp, increased concentrations of the substrate drug are likely and caution should be exercised.1
Angiotensin-converting Enzyme Inhibitors
Angioedema-type reactions have been observed during concomitant use of temsiroliimus with angiotensin-converting enzyme (ACE) inhibitors (e.g., ramipril).1 Monitor patients for signs and symptoms of angioedema when temsirolimus is given concomitantly with ACE inhibitors.1
An increased risk of intracerebral bleeding has been reported in patients receiving temsirolimus and anticoagulants concomitantly.1 Caution is advised.1
Decreased plasma sirolimus concentrations may occur during concomitant therapy with anticonvulsants that are strong CYP3A4 inducers (e.g., carbamazepine, phenobarbital, phenytoin).1, 20 Temsirolimus dosage should be increased from 25 mg weekly to 50 mg weekly; if the anticonvulsant is discontinued, temsirolimus dosage should be resumed at the previous level.1
Increased plasma sirolimus concentrations may occur during concomitant therapy with azole antifungals (e.g., itraconazole, ketoconazole, voriconazole).1, 20 Temsirolimus dosage should be decreased from 25 mg weekly to 12.5 mg weekly; if the antifungal is discontinued, an interval of 1 week should be allowed before resuming previous level of temsirolimus dosage.1
Decreased plasma sirolimus concentrations have been reported during concomitant therapy with rifamycin antimycobacterials (e.g., rifabutin, rifampin).1 Temsirolimus dosage should be increased from 25 mg weekly to 50 mg weekly; if the antimycobacterial is discontinued, temsirolimus dosage should be resumed at previous level.1
Angioedema-type reactions have been observed during concomitant therapy with calcium channel blockers (e.g., amlodipine).1 Monitor patients for signs and symptoms of angioedema when temsirolimus is given concomitantly with calcium channel blockers.1
Decreased plasma sirolimus concentrations may occur during concomitant therapy with dexamethasone.1, 20, 21 Temsirolimus dosage should be increased from 25 mg weekly to 50 mg weekly; if dexamethasone is discontinued, temsirolimus dosage should be resumed at previous level.1
Increased plasma sirolimus concentrations may occur during concomitant use with grapefruit juice.1, 20 Such concomitant use should be avoided.1
Increased plasma sirolimus concentrations may occur during concomitant therapy with HIV protease inhibitors (e.g., atazanavir, indinavir, nelfinavir, ritonavir, saquinavir).1, 20 Temsirolimus dosage should be decreased from 25 mg weekly to 12.5 mg weekly; if the HIV protease inhibitor is discontinued, an interval of 1 week should be allowed before resuming previous level of temsirolimus dosage.1
Increased plasma sirolimus concentrations may occur during concomitant therapy with macrolide anti-infectives (e.g., clarithromycin, telithromycin).1, 20 Temsirolimus dosage should be decreased from 25 mg weekly to 12.5 mg weekly; if the macrolide is discontinued, an interval of 1 week should be allowed before resuming previous level of temsirolimus dosage.1
Increased plasma sirolimus concentrations may occur during concomitant therapy with nefazodone.1, 20 Temsirolimus dosage should be decreased from 25 mg weekly to 12.5 mg weekly; if nefazodone is discontinued, an interval of 1 week should be allowed before resuming previous level of temsirolimus dosage.1
St. John's Wort ( Hypericum perforatum )
Unpredictable decreases in plasma temsirolimus concentrations have been reported with concomitant use of St. John's wort.1 Concomitant use should be avoided. 1
Increased risk of dose-limiting toxicity requiring hospitalization (e.g., grade 3/4 erythematous maculopapular rash, gout/cellulitis) has been reported with concurrent use of temsirolimus and sunitinib.1
The use of live vaccines and close contact with those who have received live vaccines should be avoided during treatment with temsirolimus.1
Temsirolimus, an inhibitor of mammalian target of rapamycin (mTOR) kinase, is an antineoplastic agent.1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 Receptor tyrosine kinases (RTKs) are involved in the initiation of various cascades of intracellular signaling events that lead to cell proliferation and/or influence processes critical to cell survival and tumor progression (e.g., angiogenesis, metastasis), inhibition of apoptosis.1, 2, 3, 4, 5, 6, 7, 8 Temsirolimus binds with high affinity to the intracellular protein FK506 binding protein-12 in vitro, forming a drug-protein complex that inhibits the activation of mTOR, which regulates cell division.1, 2, 3 This disruption of mTOR signaling suppresses proteins that regulate cell-cycle progression, thereby blocking cells in the G1 phase of the cell cycle.2, 3, 11 Inhibition of mTOR by temsirolimus also has been associated with reduced expression of hypoxia inducible factor 1α and 2α (HIF-1α and HIF-2α) in vitro, resulting in reduced expression of vascular endothelial growth factor (VEGF) and a potential antiangiogenic effect.1, 3, 4, 7, 8, 9, 10
Temsirolimus inhibited T lymphocyte activity in mice, but the effects were reversible and T lymphocyte activity returned to normal within 24 hours of discontinuance.6 No consistent effect on lymphocyte population or activation was demonstrated in humans.6 However, infections may result from immunosuppression.1
Temsirolimus is metabolized by hydrolysis to sirolimus, the principal active metabolite.1, 15, 16 Both temsirolimus and sirolimus also are metabolized by cytochrome P-450 (CYP) isoenzyme 3A4.16, 18 Although temsirolimus is metabolized to sirolimus, temsirolimus itself exhibits antitumor activity and is not considered a prodrug.15 The mean half-lives of temsirolimus and sirolimus were 17.3 hours and 54.6 hours, respectively.1 Following IV administration of a single radiolabeled dose of temsirolimus, approximately 78% of the total radioactivity is recovered in feces and 4.6% in urine within 14 days.1
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV infusion only | 25 mg/mL* | Temsirolimus Injection (supplied with diluent) | |
Torisel® (supplied with diluent) |
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions February 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
1. Wyeth Pharmaceuticals Inc. Torisel® (temsirolimus) injection prescribing information. Philadelphia, PA: 2023 Apr.
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3. Cho D, Signoretti S, Regan M et al. The role of mammalian target of rapamycin inhibitors in the treatment of advanced renal cancer. Clin Cancer Res. 2007; 13(Suppl 2):758s-63s. [PubMed 17255306]
4. Atkins MB, Ernstoff MS, Figlin RA et al. Innovations and challenges in renal cell carcinoma: summary statement from the Second Cambridge Conference. Clin Cancer Res. 2007; 13(Suppl 2):667S-70S. [PubMed 17255291]
5. Motzer RJ, Bukowski RM. Targeted therapy for metastatic renal carcinoma. J Clin Oncol. 2006; 24:5601-8. [PubMed 17158546]
6. Hidalgo M, Buckner JC, Erlichman C et al. A phase I and pharmacokinetic study of temsirolimus (CCI-779) administered intravenously daily for 5 days every 2 weeks to patients with advanced cancer. Clin Cancer Res. 2006; 12:5755-63. [PubMed 17020981]
7. Rini BI. Molecularly targeted therapy in renal cell carcinoma: where do we go from here? Expert Rev Anticancer Ther. 2006; 6:1753-60.
8. Pouessel D, Culine S. Targeted therapies in metastatic renal cell carcinoma: the light at the end of the tunnel. Expert Rev Anticancer Ther. 2006; 6:1761-7. [PubMed 17181490]
9. Hutson TE, Sonpavde G, Galsky MD. Targeting growth factor and antiangiogenic pathways in clear-cell renal cell carcinoma: rationale and ongoing trials. Clin Genitourin Cancer. 2006; 5(Suppl 1):31S-9S.
10. Escudier B. Advanced renal cell carcinoma: current and emerging management strategies. Drugs. 2007; 67:1257-64. [PubMed 17547470]
11. Reddy GK, Mughal TI, Rini BI. Current data with mammalian target of rapamycin inhibitors in advanced-stage renal cell carcinoma. Clin Genitourin Cancer. 2006; 5:110-3. [PubMed 17026798]
12. Atkins MB, Hidalgo M, Stadler WM et al. Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma. J Clin Oncol. 2004; 22:909-18. [PubMed 14990647]
13. Halbert RJ, Figlin RA, Atkins MB et al. Treatment of patients with metastatic renal cell cancer: a RAND appropriateness panel. Cancer. 2006; 107:2375-83. [PubMed 17048248]
14. Ozols RF, Herbst RS, Colson YL et al. Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening-a report from the American Society of Clinical Oncology. J Clin Oncol. 2007; 25:146-62. [PubMed 17158528]
15. Wyeth Pharmaceuticals Inc. Collegeville, PA: Personal communication. 2007 Jul 2.
16. Boni JP, Leister C, Bender G et al. Population pharmacokinetics of CCI-779: correlations to safety and pharmacogenomic responses in patients with advanced renal cancer. Clin Pharmacol Ther. 2005; 77:76-89. [PubMed 15637533]
17. Food and Drug Administration. Orphan designations pursuant to section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97 414). Rockville, MD. From FDA web site. Accessed 2007 Jul 25. [Web]
18. Office of Clinical Pharmacology, Food and Drug Administration. Clinical pharmacology and biopharmaceutics review section of FDA approval package for temsirolimus. From the FDA website. 2007 May 30. [Web]
19. Motzer RJ, Hudes GR, Curti BD et al. Phase I/II trial of temsirolimus combined with interferon alfa for advanced renal cell carcinoma. J Clin Oncol . 2007: 25:3958-64.
20. Wyeth Pharmaceuticals Inc. Collegeville, PA: Personal communication.
21. Kato M, Chiba K, Horikawa M et al. The quantitative prediction of in vivo enzyme induction caused by drug exposure from in vitro information on human hepatocytes. Drug Metab Pharmacokinet. 2005; 20:236-43. [PubMed 16141603]
22. National Cancer Institute. Renal Cell Cancer Treatment (PDQ®)-Health Professional Version. From NIH website. Accessed 2023 Feb [Web]
23. ASCO. Management of Metastatic Clear Cell Renal Cell Carcinoma: ASCO Guideline. J Clin Oncol 2022;40:2957-2995.