Adverse Event Management of Oral Mucositis in Patients with Breast Cancer

Seiler, Sabine; Kosse, Jens; Loibl, Sibylle; Jackisch, Christian

doi:10.1159/000366246

Cited by 16 publications

(28 citation statements)

References 36 publications

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“…At the time that the study was launched, it is conceivable that many of the participating centers would have had limited experience with mTOR inhibitor therapy. In the case of mTOR inhibitors, it has been shown that patient education, preventive measures, and early treatment with mouthwashes and/or lidocaine preparations help limit stomatitis and decrease dose interruptions [24, 25]. Potentially, the lack of familiarity of these centers with these measures may have resulted in higher toxicity and may partly explain the discrepancy in tolerability between phase I and phase II.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer

Baselga

Morales

Awada

et al. 2017

Breast Cancer Res Treat

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Purpose Combining the mTOR inhibitor ridaforolimus and the anti-IGFR antibody dalotuzumab demonstrated antitumor activity, including partial responses, in estrogen receptor (ER)-positive advanced breast cancer, especially in high proliferation tumors (Ki67 > 15%). Methods This randomized, multicenter, international, phase II study enrolled postmenopausal women with advanced ER-positive breast cancer previously treated with a nonsteroidal aromatase inhibitor (NCT01234857). Patients were randomized to either oral ridaforolimus 30 mg daily for 5 of 7 days (once daily [qd] × 5 days/ week) plus intravenous dalotuzumab 10 mg/kg/week or oral exemestane 25 mg/day, and stratified by Ki67 status. Due to a high incidence of stomatitis in the ridaforolimus– dalotuzumab group, two sequential, nonrandomized, reduced-dose cohorts were explored with ridaforolimus 20 and 10 mg qd × 5 days/week. The primary endpoint was progression-free survival (PFS). Results Median PFS was 21.4 weeks for ridaforolimus 30 mg qd × 5 days/week plus dalotuzumab 10 mg/kg (n = 29) and 24.3 weeks for exemestane (n = 33; hazard ratio = 1.00; P = 0.5). Overall survival and objective response rates were similar between treatment arms. The incidence of drug-related, nonserious, and serious adverse events was higher with ridaforolimus/dalotuzumab (any ridaforolimus dose) than with exemestane. Lowering the ridaforolimus dose reduced the incidence of grade 3 stomatitis, but overall toxicity remained higher than acceptable at all doses without improved efficacy. Conclusions The combination of ridaforolimus plus dalo-tuzumab was no more effective than exemestane in patients with advanced ER-positive breast cancer, and the incidence of adverse events was higher. Therefore, the combination is not being further pursued.

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Section: Discussionmentioning

confidence: 99%

A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer

Baselga

Morales

Awada

et al. 2017

Breast Cancer Res Treat

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“…The most common adverse events (AEs; all grades) related to 300 mg avapritinib in ≥35% of patients were nausea, fatigue, and anemia [26]. Supportive care and flexible dosing strategies (including dose interruptions and/or reductions), which are common strategies for managing AEs associated with multi-targeted TKIs [28][29][30][31][32], were used to manage the AEs seen with avapritinib in the NAVIGATOR phase I study.…”

Section: Introductionmentioning

confidence: 99%

Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors

et al. 2021

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Background Avapritinib, a novel inhibitor of KIT/PDGFRA, is approved in the U.S. for the treatment of adults with PDGFRA exon 18‐mutant unresectable or metastatic gastrointestinal stromal tumors (U/M GISTs). We assessed the safety of avapritinib and provide evidence‐based guidance on management of avapritinib‐associated adverse events (AEs), including cognitive effects and intracranial bleeding. Materials and Methods We performed a post hoc analysis of data from a two‐part, single‐arm dose escalation/expansion phase I study (NAVIGATOR; NCT02508532) in patients with U/M GISTs treated with oral avapritinib 30–600 mg once daily. The primary endpoints were safety and tolerability; the impact of dose modification (interruption and/or reduction) on progression‐free survival (PFS) was a secondary endpoint. Efficacy analyses were limited to patients who started avapritinib at 300 mg (approved dose). Results Of 250 patients enrolled in the study, 74.0% presented with KIT mutation and 24.8% presented with PDGFRA exon 18‐mutation; 66.8% started avapritinib at 300 mg. The most common treatment‐related AEs (any grade) were nausea (59.2%), fatigue (50.0%), periorbital edema (42.0%), anemia (39.2%), diarrhea (36.0%), vomiting (36.0%), and increased lacrimation (30.8%). No treatment‐related deaths occurred. Among 167 patients starting on 300 mg avapritinib, all‐cause cognitive effects rate (grade 1–2) was 37.0% in all patients and 52.0% in patients ≥65 years. Cognitive effects improved to a lower grade more quickly with dose modification (1.3–3.1 weeks) than without (4.9–7.6 weeks). Median PFS was 11.4 months with dose modification and 7.2 months without. Conclusion Tolerability‐guided dose modification of avapritinib is an effective strategy for managing AEs in patients with GISTs. Implications for Practice Early recognition of adverse events and tailored dose modification appear to be effective approaches for managing treatment‐related adverse events and maintaining patients on avapritinib. Dose reduction does not appear to result in reduced efficacy. Patients' cognitive function should be assessed at baseline and monitored carefully throughout treatment with avapritinib for the onset of cognitive adverse events. Dose interruption is recommended at the first sign of any cognitive effect, including grade 1 events.

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“…This toxicity has been shown in patients receiving chemotherapy with both hematologic malignancies and solid tumours such as nonHodgkin lymphoma, breast, lung, or colorectal cancer (Rosen et al 2006;Niscola et al 2007;Blijlevens et al 2008;Seiler et al 2014). Chemotherapeutic agents such as 5-fluorouracil (5-FU), anthracyclines and taxanes are associated with a high incidence of oral mucositis (Keefe et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Wound healing activity of Pluchea indica leaf extract in oral mucosal cell line and oral spray formulation containing nanoparticles of the extract

Buranasukhon

Athikomkulchai

Tadtong

et al. 2017

Pharmaceutical Biology

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Context: Pluchea indica (L.) Less (Asteraceae) is an herb used as a traditional medicine for wound healing. The chemical compounds found in Pluchea indica leaves are phenolic acids, flavonoids, anthocyanins and carotenoids.Objective: This study investigates the effect of Pluchea indica leaf ethanol extract and its nanoparticles (NPs) on cytotoxicity, cell survival and migration of human oral squamous carcinoma cell line. Materials and methods: Cell viability was measured using MTT assay to assess the effect of Pluchea indica leaf extract and NPs (1-500 lg/mL) on cytotoxicity and cell survival. The effect of Pluchea indica leaf extract and NPs on cell migration was determined by scratch assay. The % relative migration was calculated after 24, 48 and 72 h of treatment.Results: The sizes of Pluchea indica leaf extract NPs were in a range of nanometers. NPs possessed negative charge with the polydispersity index (PDI) smaller than 0.3. After the treatment for 24, 48 and 72 h, Pluchea indica leaf extract had IC 50 value of 443.2, 350.9 and 580.5 lg/mL, respectively, whereas the IC 50 value of NPs after the treatment for 24, 48 and 72 h were 177.4, 149.2 and 185.1 lg/mL, respectively. The % relative migration of cells was significantly increased when the cells were treated with 62.5 and 125 lg/mL of the extract and 62.5 lg/mL of NPs. Discussion and Conclusions: NPs increased cytotoxicity of the Pluchea indica leaf extract, increased the migration of cells at low concentration and increased colloidal stability of the extract in an oral spray formulation. ARTICLE HISTORY

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Adverse Event Management of Oral Mucositis in Patients with Breast Cancer

Cited by 16 publications

References 36 publications

A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer

A phase II study of combined ridaforolimus and dalotuzumab compared with exemestane in patients with estrogen receptor-positive breast cancer

Optimal Avapritinib Treatment Strategies for Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumors

Wound healing activity of Pluchea indica leaf extract in oral mucosal cell line and oral spray formulation containing nanoparticles of the extract

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