Direct costs associated with adverse events of systemic therapies for advanced melanoma

Copley-Merriman, Catherine; Stevinson, Kendall; Liu, Frank Xiaoqing; Wang, Jingshu; Mauskopf, Josephine; Zimovetz, Evelina; Chmielowski, Bartosz

doi:10.1097/md.0000000000011736

Cited by 21 publications

(17 citation statements)

References 14 publications

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“…8 Among these therapies, dacarbazine is reported to cause pain symptoms in animal models 10 and oncological patients. 3,31 In the present study, dacarbazine stimulated TRPA1 in cultured mouse DRG neurons and in hTRPA1-HEK293 cells, effects that were abolished by a TRPA1 antagonist. Moreover, we demonstrated that dacarbazine caused mechanical and cold allodynia in mice by TRPA1 activation and sensitization, which was reduced by TRPA1 pharmacological blockade, antioxidants and by TRPA1 gene deletion or silencing.…”

Section: Discussionsupporting

confidence: 50%

“…Antineoplastic therapy has been associated with the development of pain syndrome, which puts limits to its use and compromises the patient's quality of life . Among these therapies, dacarbazine is reported to cause pain symptoms in animal models and oncological patients . In the present study, dacarbazine stimulated TRPA1 in cultured mouse DRG neurons and in hTRPA1‐HEK293 cells, effects that were abolished by a TRPA1 antagonist.…”

Section: Discussionmentioning

confidence: 53%

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Dacarbazine alone or associated with melanoma‐bearing cancer pain model induces painful hypersensitivity by TRPA1 activation in mice

Brusco

Puma

Chiepe

et al. 2019

Intl Journal of Cancer

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Antineoplastic therapy has been associated with pain syndrome development characterized by acute and chronic pain. The chemotherapeutic agent dacarbazine, used mainly to treat metastatic melanoma, is reported to cause painful symptoms, compromising patient quality of life. Evidence has proposed that transient receptor potential ankyrin 1 (TRPA1) plays a critical role in chemotherapy‐induced pain syndrome. Here, we investigated whether dacarbazine causes painful hypersensitivity in naive or melanoma‐bearing mice and the involvement of TRPA1 in these models. Mouse dorsal root ganglion (DRG) neurons and human TRPA1‐transfected HEK293 (hTRPA1‐HEK293) cells were used to evaluate the TRPA1‐mediated calcium response evoked by dacarbazine. Mechanical and cold allodynia were evaluated after acute or repeated dacarbazine administration in naive mice or after inoculation of B16‐F10 melanoma cells in C57BL/6 mice. TRPA1 involvement was investigated by using pharmacological and genetic tools (selective antagonist or antisense oligonucleotide treatment and Trpa1 knockout mice). Dacarbazine directly activated TRPA1 in hTRPA1‐HEK293 cells and mouse DRG neurons and appears to sensitize TRPA1 indirectly by generating oxidative stress products. Moreover, dacarbazine caused mechanical and cold allodynia in naive but not Trpa1 knockout mice. Also, dacarbazine‐induced nociception was reduced by the pharmacological TRPA1 blockade (antagonism), antioxidants, and by ablation of TRPA1 expression. TRPA1 pharmacological blockade also reduced dacarbazine‐induced nociception in a tumor‐associated pain model. Thus, dacarbazine causes nociception by TRPA1 activation, indicating that this receptor may represent a pharmacological target for treating chemotherapy‐induced pain syndrome in cancer patients submitted to antineoplastic treatment with dacarbazine.

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Section: Discussionsupporting

confidence: 50%

Section: Discussionmentioning

confidence: 53%

Dacarbazine alone or associated with melanoma‐bearing cancer pain model induces painful hypersensitivity by TRPA1 activation in mice

Brusco

Puma

Chiepe

et al. 2019

Intl Journal of Cancer

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“…e monetary costs associated with trAEs were assumed to be primarily those resulting from hospitalization costs. ese were estimated as weighted averages of the costs associated with specific grades 3-4 trAEs and the frequency of occurrence of those events in the respective trials [22,33,34,44,45]. Hospitalization due to trAEs was assumed to occur for grades 3-4 only, at a rate that was estimated using insurance claims data [4].…”

Section: Estimates Of Costs and Quality Of Lifementioning

confidence: 99%

Cost-Effectiveness Analysis of Biomarker-Guided Treatment for Metastatic Gastric Cancer in the Second-Line Setting

Lauren

Ostvar

Silver

et al. 2020

Journal of Oncology

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Background. e 5-year survival rate of patients with metastatic gastric cancer (GC) is only 5%. However, trials have demonstrated promising antitumor activity for targeted therapies/immunotherapies among chemorefractory metastatic GC patients. Pembrolizumab has shown particular efficacy among patients with programmed death ligand-1 (PD-L1) expression and high microsatellite instability (MSI-H). e aim of this study was to assess the effectiveness and cost-effectiveness of biomarker-guided second-line GC treatment. Methods. We constructed a Markov decision-analytic model using clinical trial data. Our model compared pembrolizumab monotherapy and ramucirumab/paclitaxel combination therapy for all patients and pembrolizumab for patients based on MSI status or PD-L1 expression. Paclitaxel monotherapy and best supportive care for all patients were additional comparators. Costs of drugs, treatment administration, follow-up, and management of adverse events were estimated from a US payer perspective. e primary outcomes were quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) with a willingness-to-pay threshold of $100,000/QALY over 60 months. Secondary outcomes were unadjusted life years (survival) and costs. Deterministic and probabilistic sensitivity analyses were performed to evaluate model uncertainty.Results. e most effective strategy was pembrolizumab for MSI-H patients and ramucirumab/paclitaxel for all other patients, adding 3.8 months or 2.0 quality-adjusted months compared to paclitaxel. However, this strategy resulted in a prohibitively high ICER of $1,074,620/QALY. e only cost-effective strategy was paclitaxel monotherapy for all patients, with an ICER of $53,705/ QALY. Conclusion. Biomarker-based treatments with targeted therapies/immunotherapies for second-line metastatic GC patients substantially improve unadjusted and quality-adjusted survival but are not cost-effective at current drug prices.

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“…However,t he patients may be at serious risko fk illing normalc ells, developing secondary cancer, and overwhelmingi mmune systemsd ue to toxic side effects arising from nonspecific drug delivery and radiation damage. [4] Photothermalt herapy (PTT) has been developed into an effectivea pproach for cancer therapy that ablates cancer cells by using the heat generated from absorbed near-infrared( NIR) light energyw ith minimum damage fort he patient. [5] Meanwhile, NIR (l = 700-1100 nm) laser-based PTT is preferable due to the large tissue penetration depth of the NIR light, which can reach af ew centimeters.…”

Section: Introductionmentioning

confidence: 99%

“…Currently, traditional therapies include surgery, radiotherapy, and chemotherapy. However, the patients may be at serious risk of killing normal cells, developing secondary cancer, and overwhelming immune systems due to toxic side effects arising from nonspecific drug delivery and radiation damage …”

Section: Introductionmentioning

confidence: 99%

Ag@TiO₂ Nanoprisms with Highly Efficient Near‐Infrared Photothermal Conversion for Melanoma Therapy

Nie

Zhao

et al. 2019

Chemistry An Asian Journal

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Melanoma is ap rimary reason of death from skin cancer and associated with high lethality.P hotothermalt herapy (PTT) has been developed into ap owerful cancer treatment technique in recenty ears. Here, we createdalow-cost and high-performance PTT agent,A g@TiO 2 NPs, which possesses ah igh photothermal conversion efficiency of % 65 % and strong near-infrared (NIR) absorption about8 08 nm. Ag NPs were synthesized using at wo-step methoda nd coated with TiO 2 to obtain Ag@TiO 2 NPs by af acile sol-gel method. Because of the oxide, Ag@TiO 2 NPs exhibit remarkable high photothermal conversion efficiencies and biocompatibility in vivo and in vitro. Cytotoxicity and therapeutic efficiency of photothermal cytotoxicity of Ag@TiO 2 NPs were tested in B16-F10c ells and C57BL/6J mice. Under light irradiation, the elevated temperature causes cell death in Ag NPs-treated (100 mgmL À1 )c ells in vitro (both p < 0.01). In the case of subcutaneous melanoma tumor model, Ag@TiO 2 NPs (100 mgmL À1 )w ere injected into the tumor and irradiated with a8 08 nm laser of 2Wcm À2 for 1minute. As ac onsequence, the tumor volumeg radually decreased by NIRl aser irradiation with only as ingle treatment. The results demonstrate that Ag@TiO 2 NPs are biocompatible and an attractive photothermal agent for cutaneous melanoma by local delivery.[a] Dr.

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Direct costs associated with adverse events of systemic therapies for advanced melanoma

Abstract: Supplemental Digital Content is available in the text

Cited by 21 publications

References 14 publications

Dacarbazine alone or associated with melanoma‐bearing cancer pain model induces painful hypersensitivity by TRPA1 activation in mice

Dacarbazine alone or associated with melanoma‐bearing cancer pain model induces painful hypersensitivity by TRPA1 activation in mice

Cost-Effectiveness Analysis of Biomarker-Guided Treatment for Metastatic Gastric Cancer in the Second-Line Setting

Ag@TiO₂ Nanoprisms with Highly Efficient Near‐Infrared Photothermal Conversion for Melanoma Therapy

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Direct costs associated with adverse events of systemic therapies for advanced melanoma

Abstract: Supplemental Digital Content is available in the text

Cited by 21 publications

References 14 publications

Dacarbazine alone or associated with melanoma‐bearing cancer pain model induces painful hypersensitivity by TRPA1 activation in mice

Dacarbazine alone or associated with melanoma‐bearing cancer pain model induces painful hypersensitivity by TRPA1 activation in mice

Cost-Effectiveness Analysis of Biomarker-Guided Treatment for Metastatic Gastric Cancer in the Second-Line Setting

Ag@TiO2 Nanoprisms with Highly Efficient Near‐Infrared Photothermal Conversion for Melanoma Therapy

Contact Info

Product

Resources

About

Ag@TiO₂ Nanoprisms with Highly Efficient Near‐Infrared Photothermal Conversion for Melanoma Therapy