Side Effects of temsirolimus: A Synthesis of Findings from 30 Studies

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Original Abstract of the Article

Major Research Findings

Multiple studies have shown temsirolimus to be an effective mTOR inhibitor for the treatment of metastatic renal cell carcinoma. 29 However, temsirolimus can cause a variety of side effects. 3

Reasons for Side Effects

The side effects of temsirolimus are mainly due to its mTOR inhibitory action. 10 mTOR is a protein that regulates cell growth and angiogenesis, playing a role in promoting the growth of cancer cells. Temsirolimus inhibits mTOR, thereby suppressing the growth of cancer cells. However, because mTOR is also involved in the growth and function of normal cells, temsirolimus can cause various side effects.

Common Side Effects

Fatigue

Temsirolimus can cause fatigue. 24

Loss of Appetite

Temsirolimus can cause loss of appetite. 20

Diarrhea

Temsirolimus can cause diarrhea. 20

Mouth Sores

Temsirolimus can cause mouth sores. 24

High Blood Sugar

Temsirolimus can cause high blood sugar. 20

High Cholesterol

Temsirolimus can cause high cholesterol. 10

Low Phosphorus

Temsirolimus can cause low phosphorus. 10

Infections

Temsirolimus has immunosuppressive effects and can increase the risk of infections. 6

Measures to Counteract Side Effects

Fatigue

If you experience severe fatigue, consult your doctor. 13

Loss of Appetite

If you experience severe loss of appetite, consult your doctor. 13

Diarrhea

If you experience severe diarrhea, consult your doctor. 13

Mouth Sores

If you experience severe mouth sores, consult your doctor. 13

High Blood Sugar

If you are concerned about high blood sugar, consult your doctor. 13

High Cholesterol

If you are concerned about high cholesterol, consult your doctor. 13

Low Phosphorus

If you are concerned about low phosphorus, consult your doctor. 13

Infections

To prevent infections, practice good hygiene such as hand washing. 13

Comparison Between Studies

Commonalities

Multiple studies have reported fatigue, loss of appetite, diarrhea, and mouth sores as side effects of temsirolimus. 24 20 13

Differences

Some studies have reported metabolic abnormalities such as high blood sugar and high cholesterol. 10 In addition, the potential for increased risk of infection has been pointed out. 6

Cautions for Applying Research to Real Life

Temsirolimus is an effective drug for the treatment of metastatic renal cell carcinoma, but it can cause a variety of side effects. It is important to understand the risk of side effects and to take temsirolimus as directed by your doctor. 3

Limitations of Current Research

Research on the side effects of temsirolimus is still insufficient. Further research is needed.

Future Research Directions

It is necessary to elucidate the mechanism of temsirolimus side effects and develop new treatments to reduce them. In addition, guidelines for safe administration of temsirolimus need to be established.

Conclusion

Temsirolimus is an effective drug for the treatment of metastatic renal cell carcinoma, but it can cause a variety of side effects. It is important to understand the risk of side effects and to take temsirolimus as directed by your doctor. If you are concerned about side effects, consult your doctor.

Keywords
Benefit Keywords
Cancer treatment
2
Maintains effective treatment
4
Inhibition of mTOR pathway
5
Cancer treatment
Organ rejection prevention
6
Breast cancer treatment
Improved progression-free survival
7
RCC treatment
8
RCC treatment
9
Tumor growth suppression
mRCC treatment
10
Cancer treatment
11
Lower mTOR inhibitor dose
Reduced angiogenesis
12
Renal cell carcinoma treatment
13
brain tumor treatment
14
Renal cell carcinoma treatment
15
Antibiotic
Antiretroviral
Cancer treatment
16
Antinociception
Anxiolysis
17
Stable disease
Tumor response
18
Treats renal cell carcinoma
19
Metastatic RCC treatment
Progression-free survival
20
RCC treatment
21
RCC treatment
22
Treat cancer
Treat transplantation
23
Improved treatment for mRCC
24
Feasible treatment
26
Metastatic kidney cancer treatment
27
Cancer treatment
28
Hepatocellular cancer treatment
29
Progression-free survival
Response rate
30
Risk Keywords
Anemia
Fatigue
Hyperglycemia
Hyperlipidemia
Weight loss
1
Anemia
Cardiovascular morbidity
Dyspnea
Elevated lipase
Fatigue/asthenia
Hand-foot syndrome
Hyperglycemia
Hypertension
Hypophosphatemia
ICH
Lymphopenia
Mucositis/stomatitis
Neutropenia
2
Asthenia
Comorbidities
Drug interactions
Hypersensitivity
Toxicity
3
Increased infection risk
6
Quality of life impact
Side effects
7
Fatigue
Hand-foot syndrome
Hypertension
8
Hypercholesterolemia
Hypertriglyceridemia
Hypothyroidism
10
Renal cell carcinoma
11
Vascular endothelial growth factor inhibition side effects
13
Side effects
15
Amnesic
Anxiogenic
17
Fistula
Hand-foot syndrome
Hypertension
Mucositis
Pancytopenia
18
Side effects
19
Anorexia
Asthenia
Diarrhea
Hand-and-foot syndrome
Hypertension
20
Immune-related adverse event
22
Adverse reactions
23
Gastrointestinal side effects
24
Cognitive impairment
25
Gastrointestinal disorders
Hematological toxicities
Lack of efficacy
Metabolic disorders
26
Side effects
28
Pneumonitis
30
Literature analysis of 30 papers
Positive Content
26
Neutral Content
1
Negative Content
3
Article Type
1
0
1
9
29
1.

A pilot study of temsirolimus and body composition.

Author: Veasey-RodriguesHeloisa, ParsonsHenrique A, JankuFilip, NaingAung, WhelerJennifer J, TsimberidouApostolia M, KurzrockRazelle

Anemia
Fatigue
Hyperglycemia
Hyperlipidemia
Weight loss

Temsirolimus, an mTOR inhibitor, was associated with weight loss in patients with advanced solid tumors. Patients with higher grade toxicities tended to lose more body fat, suggesting a possible end-organ metabolic effect of temsirolimus.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

4.

A cross-sectional investigation of fatigue in advanced renal cell carcinoma treatment: results from the FAMOUS study.

Author: P JGoebell, AMünch, LMüller, H JHurtz, MKoska, SBusies, NMarschner

Maintains effective treatment

This study aimed to assess fatigue in patients with advanced or metastatic renal cell carcinoma (RCC) by comparing the evaluation of the physician to the one provided by the patient.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

5.

Pharmacodynamic evaluation of temsirolimus in patients with newly diagnosed advanced-stage head and neck squamous cell carcinoma.

Author: EkshyyanOleksandr, MillsGlenn M, LianTimothy, AmirghahariNazanin, RongXiaohua, Lowery-NordbergMary, AbreoFleurette, VeillonDiana M, CalditoGloria, SpeicherLisa, GlassJonathan, NathanCherie-Ann O

Inhibition of mTOR pathway

Temsirolimus, an mTOR inhibitor, significantly decreased pS6 and p4E-BP1 in tumors and pS6 and pAkt in peripheral blood mononuclear cells (PBMCs). The mTOR inhibitors may be used as adjuvant therapy for patients with minimal residual disease, and PBMCs are potential surrogate markers.

Clinical TrialA clinical trial is a planned study conducted on humans to evaluate the efficacy and safety of pharmaceuticals, medical devices, and treatment methods. It aims to explore the possibilities of new treatments and improve the health of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

6.

Molecular Pathways: Increased Susceptibility to Infection Is a Complication of mTOR Inhibitor Use in Cancer Therapy.

Author: EidenAdrian M, ZhangShuling, GaryJoy M, SimmonsJohn K, MockBeverly A

Cancer treatment
Organ rejection prevention
Increased infection risk

mTOR inhibitors have been studied for various conditions, including cancer and transplant rejection. While mTOR inhibitors are effective, long-term use can increase the risk of infections.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., IntramuralFunding provided by the NIH for research projects within the NIH.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

8.

Targeted therapies for metastatic renal cell carcinoma: an overview of toxicity and dosing strategies.

Author: HutsonThomas E, FiglinRobert A, KuhnJohn G, MotzerRobert J

RCC treatment
Fatigue
Hand-foot syndrome
Hypertension

Targeted therapies like sunitinib, sorafenib, temsirolimus, and bevacizumab have significantly improved outcomes for patients with advanced renal cell carcinoma (RCC). These therapies can be associated with side effects, such as hypertension, fatigue, hand-foot syndrome, and metabolic changes, that can be managed effectively in most patients with medical treatment or supportive interventions.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

9.

A serum metabolomic fingerprint of bevacizumab and temsirolimus combination as first-line treatment of metastatic renal cell carcinoma.

Author: JobardElodie, BlancEllen, NégrierSylvie, EscudierBernard, GravisGwenaelle, ChevreauChristine, Elena-HerrmannBénédicte, TrédanOlivier

RCC treatment

This study used metabolomics to investigate the metabolic signatures associated with targeted therapies for metastatic renal cell carcinoma (mRCC), a chemoresistant cancer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

12.

Methylnaltrexone potentiates the anti-angiogenic effects of mTOR inhibitors.

Author: SingletonPatrick A, MambetsarievNurbek, LennonFrances E, MathewBiji, SieglerJessica H, Moreno-VinascoLiliana, SalgiaRavi, MossJonathan, GarciaJoe Gn

Lower mTOR inhibitor dose
Reduced angiogenesis

Methylnaltrexone (MNTX) synergistically inhibited VEGF-induced human endothelial cell proliferation and migration with the mTOR inhibitors temsirolimus and rapamycin. This could potentially lower the therapeutic dose of mTOR inhibitors.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

13.

Tolerability of first-line therapy for metastatic renal cell carcinoma.

Author: PortaCamillo, SzczylikCezary

Renal cell carcinoma treatment
Vascular endothelial growth factor inhibition side effects

The treatment options for metastatic renal cell carcinoma (RCC) have expanded significantly in recent years, with four new agents available and others in development. This has changed the standard of first-line care, with sunitinib or bevacizumab plus interferon favored for patients with good or intermediate-risk RCC, and temsirolimus for poor-risk disease. While sunitinib and bevacizumab plus interferon have similar efficacy, treatment choice is further influenced by factors such as tumor histology, patient comorbidities, Memorial Sloan-Kettering Cancer Center risk assessment, and patient preference. This review focuses on the tolerability of first-line treatment options for clear cell RCC, considering how tolerability profiles relate to drug mechanisms of action. It describes the incidence and causes of side effects associated with vascular endothelial growth factor (VEGF) and VEGF receptor inhibition using sunitinib and bevacizumab, as well as the non-specific side effects of sunitinib. The review also considers the potential patient impact and management of these side effects, as well as those of interferon and temsirolimus. Finally, it assesses the implications of tolerability profiles for combination therapy and broader patient populations beyond those enrolled in trials.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

14.

Pharmacokinetic and tumor distribution characteristics of temsirolimus in patients with recurrent malignant glioma.

Author: KuhnJohn G, ChangSusan M, WenPatrick Y, CloughesyTimothy F, GreenbergHarry, SchiffDavid, ConradCharles, FinkKaren L, RobinsH Ian, MehtaMinesh, DeAngelisLisa, RaizerJeffrey, HessKenneth, LambornKathleen R, DanceyJanet, PradosMichael D,

brain tumor treatment

This study characterizes the pharmacokinetics of temsirolimus and its major metabolite, sirolimus, in patients receiving enzyme-inducing antiepileptic drugs (EIAED) compared with patients receiving non-EIAEDs. It also aimed to determine whether concentrations of temsirolimus or sirolimus were achieved in brain tumor tissue.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

16.

New drugs08, part 2.

Author: HussarDaniel A

Antibiotic
Antiretroviral
Cancer treatment

This article summarizes eight new drugs, including doripenem (antibiotic), maraviroc (antiretroviral), and ixabepilone (cancer drug), and provides information on their uses, indications, and potential side effects.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.

Language : English

17.

Dissociation of the pharmacological effects of THC by mTOR blockade.

Author: PuighermanalEmma, Busquets-GarciaArnau, Gomis-GonzálezMaria, MarsicanoGiovanni, MaldonadoRafael, OzaitaAndrés

Antinociception
Anxiolysis
Amnesic
Anxiogenic

This study investigates the role of the mTOR pathway in the pharmacological effects of delta9-tetrahydrocannabinol (THC). Inhibition of the mTOR pathway prevented the anxiogenic- and amnesic-like effects of THC but did not affect its anxiolytic, hypothermic, hypolocomotor, and antinociceptive effects. These findings suggest potential for targeting the endocannabinoid system to segregate beneficial and negative effects of cannabinoid agonists.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

18.

Phase I study of the antiangiogenic antibody bevacizumab and the mTOR/hypoxia-inducible factor inhibitor temsirolimus combined with liposomal doxorubicin: tolerance and biological activity.

Author: MoroneyJohn, FuSiqing, MoulderStacy, FalchookGerald, HelgasonThorunn, LevenbackCharles, HongDavid, NaingAung, WhelerJennifer, KurzrockRazelle

Stable disease
Tumor response
Fistula
Hand-foot syndrome
Hypertension
Mucositis
Pancytopenia

The combination of bevacizumab, temsirolimus, and liposomal doxorubicin was well tolerated and showed promising activity in patients with various advanced malignancies, especially in patients with parotid gland adenocarcinoma, metaplastic breast cancer, and endometrial endometrioid carcinoma.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, N.I.H., ExtramuralResearch funding provided by the NIH to external research institutions and researchers.

Language : English

20.

[Renal cell carcinoma and antiangiogenic therapies].

Author: PouesselDamien, CulineStéphane, VerhoestGregory, PatardJean-Jacques

Metastatic RCC treatment
Progression-free survival
Anorexia
Asthenia
Diarrhea
Hand-and-foot syndrome
Hypertension

Targeted therapies such as sunitinib, sorafenib, bevacizumab, and temsirolimus have shown promise in treating metastatic renal cell carcinoma (RCC), offering improved progression-free survival and overall survival compared to traditional immunotherapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : French

21.

Novel agents for renal cell carcinoma require novel selection paradigms to optimise first-line therapy.

Author: SchmidingerManuela, ZielinskiChristoph C

RCC treatment

The availability of first-line therapies for metastatic renal cell carcinoma (RCC) has increased rapidly with the introduction of three novel agents: sunitinib, temsirolimus, and bevacizumab (in combination with interferon [IFN]). This expansion makes selecting the optimal therapy for individual patients more challenging and crucial. Currently, a treatment algorithm based on tumor histology and patient risk status guides clinical practice, but it doesn't always identify specific treatment for individual patients, particularly for those with favorable or intermediate-risk clear cell RCC. Treatment selection for these patients should consider potential for cure and optimal progression-free survival (PFS) with good tolerability and quality of life. Bevacizumab combined with IFN may be the treatment of choice for patients with a realistic opportunity for cure. However, sunitinib and bevacizumab combined with IFN yield similar PFS. Therefore, if optimal PFS is the treatment goal, other factors, such as patient-related factors (needs, circumstances, comorbidities) and the associated side effects of bevacizumab combined with IFN and sunitinib, should be considered. The review discusses these factors in detail, highlighting factors that may lead to the selection of bevacizumab combined with IFN or sunitinib for individual patients.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

22.

Frequency of pre-treatment may not increase the immune-related adverse events of RCC patients treated with nivolumab.

Author: MizutaniKosuke, ItoToshiki, TakaharaKiyoshi, AndoRyosuke, IshiharaTakuma, YasuiTakahiro, ShirokiRyoichi, MiyakeHideaki, KoieTakuya

RCC treatment
Immune-related adverse event

This study investigates the association between immune-related adverse events (irAEs) due to nivolumab treatment and the number of prior targeted therapies in patients with renal cell carcinoma (RCC). The results suggest that the number of prior therapies is associated with higher grades of irAEs, but not the incidence of irAEs.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Observational StudyResearch that observes and collects data on participants' behavior and outcomes in their natural state, without intervention.

Language : English

25.

The Route to 'Chemobrain' - Computational probing of neuronal LTP pathway.

Author: FahimAmmad, RehmanZaira, BhattiMuhammad Faraz, VirkNasar, AliAmjad, RashidAmir, ParachaRehan Zafar

Cognitive impairment

This study investigates the potential off-target interactions of chemotherapeutic drugs with proteins involved in neuronal long-term potentiation (LTP). Several drugs were identified as potential LTP pathway inhibitors, suggesting possible interference with neurotransmission and synaptic plasticity in cancer patients receiving chemotherapy.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

26.

Gemcitabine Combined with the mTOR Inhibitor Temsirolimus in Patients with Locally Advanced or Metastatic Pancreatic Cancer. A Hellenic Cooperative Oncology Group Phase I/II Study.

Author: KaravasilisVasilios, SamantasEpaminontas, KoliouGeorgia-Angeliki, Kalogera-FountzilaAnna, PentheroudakisGeorge, VarthalitisIoannis, LinardouHelena, RallisGrigorios, SkondraMaria, PapadopoulosGeorgios, PapatsibasGeorge, SgourosJoseph, GoudopoulouAthina, KalogerasKonstantine T, DervenisChristos, PectasidesDimitrios, FountzilasGeorge

Feasible treatment
Gastrointestinal disorders
Hematological toxicities
Lack of efficacy
Metabolic disorders

The combination of gemcitabine (G) and temsirolimus (T) was feasible in patients with locally advanced or metastatic pancreatic carcinoma (MPC) with manageable side effects. However, the combination lacked clinical efficacy, with a median progression-free survival of 2.69 months and a 6-month progression-free survival rate of 30.9%.

Clinical Trial, Phase IThe first stage of clinical trials in humans. Evaluates the safety, tolerability, and pharmacokinetics of a new drug/treatment.
Clinical Trial, Phase IIA Phase II trial is a trial that further evaluates the efficacy and safety of a new drug or treatment, whose safety has been confirmed to some extent in a Phase I trial, in a small number of patients.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Multicenter StudyResearch conducted in collaboration with multiple research institutions. It aims to collect a wide range of data and obtain more generalizable results.
Randomized Controlled TrialA clinical trial that randomly assigns participants to treatment and control groups to evaluate the effects of an intervention.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Language : English

27.

Addition of bevacizumab to temsirolimus in kidney cancer patients.

Author: BoyleH, NégrierS

Metastatic kidney cancer treatment

Adding bevacizumab to temsirolimus improved disease control and side effects in two patients with metastatic kidney cancer who had progressed on the mTOR inhibitor alone.

Case ReportsIn the medical field, a report that describes in detail a unique case, an unusual medical condition, or the effect of a treatment. Provides new insights and possibilities for treatment through individual patient cases.

Language : English

28.

Toxicities associated with the administration of sorafenib, sunitinib, and temsirolimus and their management in patients with metastatic renal cell carcinoma.

Author: BhojaniNaeem, JeldresClaudio, PatardJean-Jacques, PerrottePaul, SuardiNazareno, HuttererGeorg, PatenaudeFrançois, OudardStéphane, KarakiewiczPierre I

Cancer treatment
Side effects

Sorafenib, sunitinib, and temsirolimus, three kinase inhibitors used to treat cancer, all have a range of side effects that can be managed effectively.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.
Systematic ReviewA review that systematically collects, evaluates, and integrates relevant research to answer a specific research question.

Language : English

29.

mTOR inhibitors for hepatocellular cancer: a forward-moving target.

Author: TreiberGerhard

Hepatocellular cancer treatment

mTOR is a protein that plays a key role in cell growth and the formation of blood vessels. In about half of people with liver cancer, the mTOR pathway is overactive. mTOR inhibitors are medications that block the mTOR pathway and have been shown to reduce tumor growth and blood vessel formation in laboratory studies. Clinical trials are ongoing to evaluate the use of mTOR inhibitors in treating advanced liver cancer.

Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.
ReviewAn article that critically examines existing research on a particular topic and summarizes the current state of knowledge in the field.

Language : English

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