Incidence of Melanoma in Catalonia, Spain, Is Rapidly Increasing in the Elderly Population. A Multicentric Cohort Study

Podlipnik, Sebastián; Carrera, Cristina; Boada, Aram; Richarz, Nina A.; Marcoval, Joaquim; Ferreres, J.R.; Bodet, D.; Martí, Rosa M.; Segura, Sònia; Sàbat, Mireia; Dalmau, Joan; Quintana, Mònica; Azón-Masoliver, Antoni; Curcó, N.; Formigón, M; Olivella-Garcés, María Rosa; Zaballos, Pedro; Solà, Joaquím Fernández; Galvany, Loida; Baliu-Piqué, Carola; Alegre, M.; Pasquali, Paola; Malvehy, Josep; Puig, Susana

doi:10.3390/jcm9113396

Cited by 25 publications

(15 citation statements)

References 35 publications

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“…The incidence of melanoma is keeping a worldwide increase. Incidence in Europe is about 25 cases per 100,000 population, while in Australia it reaches a rate of 60 new cases per 100,000 ( Podlipnik et al, 2020 ; Conforti and Zalaudek, 2021 ). Total melanoma incidence was higher in male than female in US individuals (limited to white race), Canada, Australia, and New Zealand.…”

Section: Introductionmentioning

confidence: 99%

Phase I pharmacokinetic study of an oral, small-molecule MEK inhibitor tunlametinib in patients with advanced NRAS mutant melanoma

Zhao

Wang²,

Wang³

et al. 2022

Front. Pharmacol.

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Background: Malignant melanoma is an aggressive disease. Tunlametinib (HL-085) is a potent, selective, and orally bioavailable MEK1/2 inhibitor. The objective of this study was to determine the pharmacokinetics (PK) of tunlametinib and its main metabolite M8 in patients with NRAS-mutant melanoma following a single dose and multiple doses in a phase I safety and PK study.Methods: A multiple-center phase I study was performed in patients with melanoma including dose-escalation phase and dose-expansion phase. PK following a single oral dose and multiple doses of 0.5–18 mg twice daily was assessed.Results: A total of 30 participants were included in the dose escalation phase and then 11 patients were included in the dose-expansion phase (12 mg twice daily). Tunlametinib plasma concentration rapidly increased after dosing, with a Tmax of 0.5–1 h. Mean elimination half-life (t1/2) was dose-independent and had a range from 21.84 to 34.41 h. Mean apparent clearance (CL/F) and distribution volume (V/F) were 28.44–51.93 L/h and 1199.36–2009.26 L, respectively. The average accumulation ratios of AUC and Cmax after the multiple administration of tunlametinib were 1.64–2.73 and 0.82–2.49, respectively. Tunlametinib was rapidly transformed into the main metabolite M8 and M8 reached the peak concentration about 1 h after administration. Mean t1/2 of M8 was 6.1–33.54 h. The body exposure of M8 in plasma was 36%–67% of that of tunlametinib. There were general dose-proportional increases in maximum concentration (Cmax) and area under the curve (AUC) of tunlametinib and M8 both in the single dose phase and in the multiple doses phase.Conclusion: Tunlametinib was absorbed rapidly and eliminated at a medium speed after drug withdrawal. Pharmacokinetic body exposure increased in general dose-proportional manner from 0.5 mg up to 18 mg. Slight accumulation was found after multiple oral doses. The pharmacokinetics of tunlametinib and its metabolite suggest that twice daily dosing is appropriate for tunlametinib.

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Section: Introductionmentioning

confidence: 99%

Phase I pharmacokinetic study of an oral, small-molecule MEK inhibitor tunlametinib in patients with advanced NRAS mutant melanoma

Zhao

Wang²,

Wang³

et al. 2022

Front. Pharmacol.

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“…Melanoma only accounts for 1-2% of all cancer cases worldwide and less than 5% of skin cancers, but is responsible for around 95% of deaths due to skin cancer [ 3 ]. Melanoma can also appear early in life and is the solid tumor that causes the greatest number of potential life-years lost [ 3 , 4 ].…”

Section: Introductionmentioning

confidence: 99%

Temporal Trends in the Incidence and Mortality of Skin Malignant Melanoma in China from 1990 to 2019

Bai

Huang

Li³

et al. 2021

Journal of Oncology

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Purpose. Skin malignant melanoma (SMM) is one of the fastest-growing cancers in China, with a poor prognosis, high invasiveness, and high mortality rate. The aim of this study was to determine the long-term trends in the incidence and mortality of SMM in China between 1990 and 2019. Patients and Methods. Incidence and mortality data were extracted from the Global Burden of Disease Study 2019 and were analyzed using an age-period-cohort framework. Results. The annual incidence net drifts were 3.523% (95% confidence interval (CI): 3.318% to 3.728%) and 3.779% (95% CI: 3.585% to 3.974%) for males and females, respectively, while the corresponding annual net drifts of mortality were −0.754% (95% CI: −1.073% to −0.435%) and –0.826% (95% CI: −1.164% to −0.487%). The local drift from 1990 to 2019 was highest in males aged from 25 to 29 years. After controlling for period deviations in a single birth cohort, the SMM incidence and mortality increased exponentially with age for both sexes. Similar increasing monotonic trends were found for period and cohort effects on the incidence, while a declining trend was found for mortality. Conclusion. While the age-standardized mortality rate of SMM in China has decreased in both sexes over the past 30 years, the crude incidence rate, age-standardized incidence rate, and crude mortality rate have all increased. SMM may greatly threaten the health of the elderly in China due to the aging population. Appropriate changes should be made to raise the awareness, reduce the exposure to risk factors, and promote the early detection of SMM.

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“…Melanoma is an aggressive skin cancer with an increasing incidence. 1 Melanoma is more common in lower latitudes and in older patients compared with higher latitudes and younger patients. 2 Melanoma is associated with a high mortality rate and accounts for a high proportion of cancer-related years of life lost per death from the disease.…”

Section: Introductionmentioning

confidence: 99%

Metastatic melanoma presenting with dyspepsia: a case report

2022

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The gastrointestinal tract is an uncommon site for metastasis. Gastrointestinal metastasis of melanoma is usually asymptomatic, often affects the small intestine (81.1%) and the colon (15.1%), and rarely affects the stomach. Our patient was a 40-year-old man presenting with gradually worsening dyspepsia of a few weeks’ duration. He did not mention other gastrointestinal symptoms, and he was not anemic. He had a history of auricular melanoma, which was resected. A black lesion with a diameter of approximately 20 mm was detected in the body of his stomach during upper gastrointestinal endoscopy. Biopsies were taken, and the diagnosis of metastatic melanoma was confirmed by immunohistochemistry (IHC). A gastrointestinal work-up, computed tomography (CT), and positron-emission tomography (PET) did not reveal additional lesions. The lesion in the stomach was resected, and a new course of chemotherapy was initiated. A lower threshold should be considered for gastrointestinal work-up in patients with melanoma.

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Incidence of Melanoma in Catalonia, Spain, Is Rapidly Increasing in the Elderly Population. A Multicentric Cohort Study

Cited by 25 publications

References 35 publications

Phase I pharmacokinetic study of an oral, small-molecule MEK inhibitor tunlametinib in patients with advanced NRAS mutant melanoma

Phase I pharmacokinetic study of an oral, small-molecule MEK inhibitor tunlametinib in patients with advanced NRAS mutant melanoma

Temporal Trends in the Incidence and Mortality of Skin Malignant Melanoma in China from 1990 to 2019

Metastatic melanoma presenting with dyspepsia: a case report

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