<scp>S</scp>afety profile of platinum-based chemotherapy in the treatment of advanced non-small cell lung cancer in elderly patients

Rossi, Antonio; Maione, Paolo; Gridelli, Cesare

doi:10.1517/14740338.4.6.1051

Cited by 20 publications

(14 citation statements)

References 102 publications

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“…At the same time several treatment options should still be evaluated as for example: doublets with and without platinum, maintenance strategies and biologic agents [73] . A third-generation agent given alone is at the time the recommended option for elderly advanced NSCLC patients [79][80][81] . The choice for the best agent should consider together expected toxicities, pharmacokinetics aspects, liver-kidney function and co-existing illnesses.…”

Section: Resultsmentioning

confidence: 99%

Advanced non-small cell lung cancer in elderly patients: A review

Buffoni¹

2015

WJR

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Over 50% of patients diagnosed with non-smallcell lung cancer (NSCLC) are 65 years old while 30% exceed 70 years old. Comparing elderly patients to their younger counterpart they poorly tolerate chemotherapy due to progressive reduction of organ function and age-related co-existing pathologies. Due to this reason elderly are usually excluded from platinum-based chemotherapy, which still represent the standard of care for advanced NSCLC. In every-day practice, single-agent schedule with a third-generation drug is the recommended option for elderly patients with advanced NSCLC. A modest increase in toxicity for elderly patients has been demonstrated by subgroup analyses concluding for platinum-based combination chemotherapy being similar in young patients and fit elderly. Even though the cited evidence, feasibility of chemotherapy based on platinum remains an open question. Prospective randomised trials are warranted in order to change guide lines and give the clinicians a new therapeutic option. Recent emerging role of molecular target in selecting patients for new targeted therapies suggest dedicated trials for elderly patients. The same is for more accurate evaluation of elderly patients with increasing evidence for a comprehensive geriatric assessment as a valid tool for customized treatment in NSCLC elderly patients. Suitable evidences for the treatment of elderly patients affected by advanced NSCLC together with more appropriate and validated tools for patients selection are reviewed along the manuscript.

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Section: Resultsmentioning

confidence: 99%

Advanced non-small cell lung cancer in elderly patients: A review

Buffoni¹

2015

WJR

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“…However, elderly patients were more sensitive to docetaxel exposure than nonelderly patients, resulting in different recommended doses [24]. The safety profile of cisplatin-based chemotherapy in the elderly has been fully reviewed elsewhere [25]. Geriatric assessment is a multidimensional, multidisciplinary approach, involving functional status, comorbidity, socioeconomic status, cognitive status, emotional status, nutritional status and the presence of geriatric symptoms [1].…”

Section: Assessment Of Elderly Nsclc Patientsmentioning

confidence: 99%

Age-Related Genetic Abnormalities: The Achilles‘ Heel for Customizing Therapy in Elderly Lung Cancer Patients

Rosell

Santarpía

Morán

et al. 2007

Personalized Medicine

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Aging and cancer are closely related, and DNA repair systems, mainly involving the nucleotide excision repair pathway, have an important caretaker function in both processes. More than half of non-small cell lung cancer patients are elderly, and the expression of some genes involved in the mitotic checkpoint, such as BubR1, declines with aging. Cisplatin-based chemotherapy is the standard treatment for advanced non-small cell lung cancer; if performance status is good, both elderly and younger patients can tolerate this treatment equally well. Customized cisplatin treatment, based on reduction of the nucleotide excision repair pathway function, could be an attractive approach, and the assessment of mitotic checkpoint genes can be used for selecting docetaxel treatment. Epidermal growth factor receptor (EGFR) mutations are particularly frequent in elderly lung cancer patients who are never-smokers and constitute an attractive target for treatment with EGFR tyrosine kinase inhibitors.

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“…3,4 However, DDP-based regimens often have severe side effects, which are a frequent cause of poor tolerability, limited therapeutic efficacy, and drug discontinuation. 5 Therefore, novel strategies for treatment of lung cancer are urgently needed.…”

Section: Introductionmentioning

confidence: 99%

Reversal of multidrug resistance by cisplatin-loaded magnetic Fe3O4 nanoparticles in A549/DDP lung cancer cells in vitro and in vivo

Chen²,

Xu³

et al. 2013

IJN

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Abstract:The purpose of this study was to explore whether magnetic Fe 3 O 4 nanoparticles (Fe 3 O 4 -MNP) loaded with cisplatin (Fe 3 O 4 -MNP-DDP) can reverse DDP resistance in lung cancer cells and to investigate mechanisms of multidrug resistance in vitro and in vivo. MTT assay showed that DDP inhibited both A549 cells and DDP-resistant A549 cells in a timedependent and dose-dependent manner, and that this inhibition was enhanced by Fe 3 O 4 -MNP. An increased rate of apoptosis was detected in the Fe 3 O 4 -MNP-DDP group compared with a control group and the Fe 3 O 4 -MNP group by flow cytometry, and typical morphologic features of apoptosis were confirmed by confocal microscopy. Accumulation of intracellular DDP in the Fe 3 O 4 -MNP-DDP group was greater than that in the DDP group by inductively coupled plasma mass spectrometry. Further, lower levels of multidrug resistance-associated protein-1, lung resistance-related protein, Akt, and Bad, and higher levels of caspase-3 genes and proteins, were demonstrated by reverse transcriptase polymerase chain reaction and Western blotting in the presence of Fe 3 O 4 -MNP-DDP. We also demonstrated that Fe 3 O 4 -MNP enhanced the effect of DDP on tumor growth in BALB/c nude mice bearing DDP-resistant human A549 xenografts by decreasing localization of lung resistance-related protein and Ki-67 immunoreactivity in cells. There were no apparent signs of toxicity in the animals. Overall, these findings suggest potential clinical application of Fe 3 O 4 -MNP-DDP to increase cytotoxicity in lung tumor xenografts.

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Safety profile of platinum-based chemotherapy in the treatment of advanced non-small cell lung cancer in elderly patients

Cited by 20 publications

References 102 publications

Advanced non-small cell lung cancer in elderly patients: A review

Advanced non-small cell lung cancer in elderly patients: A review

Age-Related Genetic Abnormalities: The Achilles‘ Heel for Customizing Therapy in Elderly Lung Cancer Patients

Reversal of multidrug resistance by cisplatin-loaded magnetic Fe3O4 nanoparticles in A549/DDP lung cancer cells in vitro and in vivo

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