Management of adverse events associated with the use of everolimus in patients with advanced renal cell carcinoma

Porta, Camillo; Osanto, Susanne; Ravaud, Alain; Climent, Miguel Ángel; Vaishampayan, Ulka N.; White, Dorothy A.; Creel, Patricia; Dickow, Brenda; Fischer, Pamela J.; Gornell, Suzanne Sweeney; Meloni, Federica; Motzer, Robert J.

doi:10.1016/j.ejca.2011.02.014

Cited by 130 publications

(160 citation statements)

References 26 publications

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“…This outcome is consistent with the report that topical clobetasol treatment reduced aphthous ulceration in renal transplant patients receiving sirolimus 50. In addition, the steroid mouth rinses and “magic” mouthwashes, often used for the palliative management of chemotherapy‐induced stomatitis, have been suggested for the prevention and treatment of mIAS 17, 46. A case report of a patient with mIAS for whom treatment included topical dexamethasone, intralesional injections of the corticosteroid triamcinolone, and magic mouthwash oral rinse demonstrated significant improvement in the signs and symptoms of mIAS lesions 47.…”

Section: Preventing and Treating Mtor Inhibitor–associated Stomatitissupporting

confidence: 87%

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Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice

et al. 2016

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In recent years oral mucosal injury has been increasingly recognized as an important toxicity associated with mammalian target of rapamycin (mTOR) inhibitors, including in patients with breast cancer who are receiving everolimus. This review addresses the state‐of‐the‐science regarding mTOR inhibitor‐associated stomatitis (mIAS), and delineates its clinical characteristics and management. Given the clinically impactful pain associated with mIAS, this review also specifically highlights new research focusing on the study of the molecular basis of pain. The incidence of mIAS varies widely (2–78%). As reported across multiple mTOR inhibitor clinical trials, grade 3/4 toxicity occurs in up to 9% of patients. Managing mTOR‐associated oral lesions with topical oral, intralesional, and/or systemic steroids can be beneficial, in contrast to the lack of evidence supporting steroid treatment of oral mucositis caused by high‐dose chemotherapy or radiation. However, steroid management is not uniformly efficacious in all patients receiving mTOR inhibitors. Furthermore, technology does not presently exist to permit clinicians to predict a priori which of their patients will develop these lesions. There thus remains a strategic need to define the pathobiology of mIAS, the molecular basis of pain, and risk prediction relative to development of the clinical lesion. This knowledge could lead to novel future interventions designed to more effectively prevent mIAS and improve pain management if clinically significant mIAS lesions develop.

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Section: Preventing and Treating Mtor Inhibitor–associated Stomatitissupporting

confidence: 87%

“…As noted in Table 3, prophylactic measures to prevent mIAS have been proposed by expert panel groups 17, 46, 47. In comparison, study of the use of topical or systemic corticosteroids for mIAS treatment suggests their possible efficacy 14, 48, 49.…”

Section: Preventing and Treating Mtor Inhibitor–associated Stomatitismentioning

confidence: 99%

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice

et al. 2016

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“…High incidence rates (56%) of stomatitis or mucositis have also been reported in randomized clinical trials of the approved mTOR inhibitor everolimus in combination treatments for breast cancer (45,46). Patients should be educated about early detection and maintaining good preventative oral hygiene to minimize the risk of occurrence of this adverse event (41,47,48).…”

Section: Tumor Responsementioning

confidence: 99%

A Phase I Trial of Combined Ridaforolimus and MK-2206 in Patients with Advanced Malignancies

Gupta

Argilés

Münster

et al. 2015

Clinical Cancer Research

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Purpose: The PI3K/Akt/mTOR signaling pathway is aberrantly activated in many cancers. Combining ridaforolimus, an mTOR inhibitor, with MK-2206, an Akt inhibitor, may more completely block the PI3K pathway and inhibit tumor growth.Experimental Design: This phase I study assessed dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) for the combination of oral ridaforolimus plus oral MK-2206 in patients with advanced solid tumors. Efficacy was evaluated in patients with biomarker-identified estrogen receptor-positive breast cancer (low RAS gene signature and high Ki67 index) or castrationresistant prostate cancer (PTEN deficiency) with PI3K pathway addiction.Results: Thirty-five patients were enrolled: 11 patients in part A (three breast cancer) and 24 biomarker-eligible patients in part B (16 breast cancer, eight prostate cancer). One patient with breast cancer from part A was also found to be biomarker-eligible when tested after she had clinical response. The MTD was 10 mg/d ridaforolimus 5 d/wk þ 90 mg/wk MK-2206; 1 of 17 patients experienced DLT (grade 3 rash) at this dose. The most common adverse events at MTD were rash (44.4%), stomatitis (38.9%), diarrhea (27.8%), and decreased appetite (27.8%). By investigator assessment, 2 of 16 (12.5%) evaluable patients with breast cancer had partial response; by central assessment, 2 of 14 (14.3%) evaluable patients had complete response. Two patients had durable stable disease (SD) for 416 and 285 days, respectively. No patients with prostate cancer responded; one patient had SD for !6 months.Conclusions: Combination ridaforolimus and MK-2206 showed promising activity and good tolerability in heavily pretreated patients with hormone-positive and -negative breast cancer exhibiting PI3K pathway dependence.

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“…42 In terms of patient education, physicians should inform patients to avoid exposure to direct sunlight and wear protective clothes covering the head, face, hands, arms and legs. 43 In addition, a sunscreen with dual UVA/UVB protection should be generously applied at least four-hourly whenever exposure to the sun is a possibility (more frequent application may be necessary for patients who sweat excessively or during swimming).…”

Section: Ta B L E 2 Recommended Management Of Various Skin Conditionsmentioning

confidence: 99%

Management of epidermal growth factor receptor tyrosine kinase inhibitor‐related cutaneous and gastrointestinal toxicities

Tan

Chin

et al. 2017

Asia-Pac J Clncl Oncology

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Patients with advanced stage non-small cell lung cancer with sensitizing epidermal growth factor receptor (EGFR) mutations using EGFR tyrosine kinase inhibitors (TKIs) such as erlotinib, gefitinib and afatinib as first-line treatment had better progression-free survival, overall response rate and quality of life than those on chemotherapy. Although EGFR TKIs are commonly associated with skin-related (rash, xerosis and paronychia) and gastrointestinal-related (diarrhea and stomatitis) adverse events (AEs), these effects are usually mild. But severe cases can occur, significantly affecting patient's well-being, treatment compliance and quality of life. Therefore, patient education, early diagnosis, and prophylactic treatment are important strategies to optimally manage EGFR TKI-related adverse effects. In this review, we summarize the commonly encountered EGFR TKI-related AEs and provide a current overview of AE management in local practice with a focus on Asian patients. K E Y W O R D Sadverse drug events, gastrointestinal tract, mutations, non-small cell lung cancer, skin BACKGROUNDEighty percent of lung cancers are advanced-stage non-small cell lung cancer (NSCLC). (1) Epidermal growth factor receptor (EGFR) gene mutation, which is a major and potent oncogenic driver in NSCLC is a therapeutic target, with EGFR tyrosine kinase inhibitors (EGFR TKIs), altering the pattern of care in patients with advanced stage NSCLC.With EGFR TKIs (erlotinib, gefitinib and afatinib) as first-line treatment for patients with advanced stage NSCLC with sensitizing EGFR mutations, higher progression-free survival, overall response rate and quality of life than chemotherapy can be achieved. 1 These drugs are generally well tolerated as they have a predictable toxicity profile and less serious toxicities than traditional cytotoxic chemotherapy. 2 Nevertheless, EGFR TKIs can still produce severe adverse events (AEs) and impair quality of life.This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. wileyonlinelibrary.com/journal/ajco 23

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Management of adverse events associated with the use of everolimus in patients with advanced renal cell carcinoma

Cited by 130 publications

References 26 publications

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice

Oral mucosal injury caused by mammalian target of rapamycin inhibitors: emerging perspectives on pathobiology and impact on clinical practice

A Phase I Trial of Combined Ridaforolimus and MK-2206 in Patients with Advanced Malignancies

Management of epidermal growth factor receptor tyrosine kinase inhibitor‐related cutaneous and gastrointestinal toxicities

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