Patterns of platinum drug use in an acute care setting: a retrospective study

Armstrong-Gordon, Evangeline; Gnjidic, Danijela; McLachlan, Andrew J.; Hosseini, Bayan; Grant, Andrew; Beale, Philip; Wheate, Nial J.

doi:10.1007/s00432-018-2669-6

Cited by 23 publications

(18 citation statements)

References 26 publications

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“…For instance, cisplatin is a component in more active clinical trials worldwide than any other anticancer agent . Unfortunately, intrinsic and acquired resistance due to mutations remain as major obstacles for the use of platinum drugs in treating cancer. − Accordingly, many new types of platinum compounds have been designed to overcome platinum resistance: trans -Pt(II) compounds, polynuclear Pt(II) compounds, Pt(IV) prodrugs, , Pt(IV) prodrugs activated by visible light, glucose–platinum conjugates, , as well as new drug delivery systems are being evaluated. , Cisplatin, carboplatin, oxaliplatin, and arsenic trioxide (As 2 O 3 ) − are the only nonradioactive metal/metalloid-containing drugs approved by the FDA to treat cancer. These drugs are able to trigger apoptotic cell death, in the case of platinum compounds through direct platinum binding to nuclear DNA, , and in the case of As 2 O 3 most likely through the thiophilic As(III) binding to cysteine rich proteins and by its ability to displace zinc from zinc-finger-containing regulatory proteins. − …”

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confidence: 99%

Arsenoplatin-1 Is a Dual Pharmacophore Anticancer Agent

et al. 2019

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Arsenoplatins are adducts of two chemically important anticancer drugs, cisplatin and arsenic trioxide, that have a Pt(II) bond to an As(III) hydroxide center. Screens of the NCI-60 human tumor cell lines reveal that arsenoplatin-1 (AP1), [Pt(μ-NHC(CH 3)O) 2 ClAs(OH) 2 ], the first representative of this novel class of anti-cancer agents, displays a superior activity profile relative to the parent drugs As 2 O 3 or cisplatin in majority of cancer cell lines tested. These activity profiles are important because the success of arsenic trioxide in blood cancers (such as APL) has not been seen in solid tumors due to the rapid clearance of arsenous acid from the body. To understand the biological chemistry of these compounds, we evaluated interactions of AP-1 with the two important classes of biomolecules-proteins and DNA. The first structural studies of AP-1 bound to model proteins reveal that platinum(II) binds the Nε of His in a manner that preserves the Pt-As bond. We find that AP-1 readily enters cells and binds to DNA with an intact Pt-As bond (Pt:As ratio of 1). At longer incubation times, however, the Pt:As ratio in DNA samples increases, suggesting that the Pt-As bond breaks and releases the As(OH) 2 moiety. We conclude that

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confidence: 99%

Arsenoplatin-1 Is a Dual Pharmacophore Anticancer Agent

et al. 2019

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“…Today, the platinum-based drugs cisplatin, carboplatin, and oxaliplatin are widely used and are among the most prominent examples of the use of metals in medicine. A recent study suggested that, in one hospital setting, approximately 50% of chemotherapeutic treatments involved a platinum anticancer drug [6,7]. Since these early discoveries, various kinds of metal-containing compounds have been investigated for their applications in therapy and diagnostics.…”

Section: Metal Complexes: Attractive Alternativesmentioning

confidence: 99%

Metal complexes for therapeutic applications

Karges¹,

Stokes²,

Cohen³

2021

Trends in Chemistry

101

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“…For example, the cure rate of patients diagnosed with testicular cancer increased from 10 to over 95% after the introduction of cisplatin (FDA approval in 1978) [7–9]. At present, cisplatin and its analogues carboplatin and oxaliplatin (Fig 1) are extensively used in cancer chemotherapy, usually in combinations with other drugs [8,10–12]. Indeed, 36 of 75 anticancer treatment regimens listed in Martindale drug reference book are platinum-based [13], while Pt drugs are prescribed to nearly halve of the patients undergoing chemotherapy in Australia [12].…”

Section: Introductionmentioning

confidence: 99%

“…At present, cisplatin and its analogues carboplatin and oxaliplatin (Fig 1) are extensively used in cancer chemotherapy, usually in combinations with other drugs [8,10–12]. Indeed, 36 of 75 anticancer treatment regimens listed in Martindale drug reference book are platinum-based [13], while Pt drugs are prescribed to nearly halve of the patients undergoing chemotherapy in Australia [12]. Furthermore, preclinical and clinical efficacy of new anticancer drug candidates is commonly trialed in combination with platinum chemotherapeutics [11,14].…”

Section: Introductionmentioning

confidence: 99%

Screening-based approach to discover effective platinum-based chemotherapies for cancers with poor prognosis

et al. 2019

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Drug combinations are extensively used to treat cancer and are often selected according to complementary mechanisms. Here, we describe a cell-based high-throughput screening assay for identification of synergistic combinations between broadly applied platinum-based chemotherapeutics and drugs from a library composed of 1280 chemically and pharmacologically diverse (mostly FDA approved) compounds. The assay was performed on chemoresistant cell lines derived from lung (A549) and pancreatic (PANC-1) carcinoma, where platinum-based combination regimens are currently applied though with limited success. The synergistic combinations identified during the screening were validated by synergy quantification using the combination index method and via high content fluorescent microscopy analysis. New promising synergistic combinations discovered using this approach include compounds currently not used as anticancer drugs, such as cisplatin or carboplatin with hycanthone and cisplatin with spironolactone in pancreatic carcinoma, and carboplatin and deferoxamine in non-small cell lung cancer. Strong synergy between cisplatin or carboplatin and topotecan in PANC-1 cells, compared to A549 cells, suggests that this combination, currently used in lung cancer treatment regimens, could be applied to pancreatic carcinoma as well. Several drugs used to treat diseases other than cancer, including pyrvinium pamoate, auranofin, terfenadine and haloprogin, showed strong cytotoxicity on their own and synergistic interactions with platinum drugs. This study demonstrates that non-obvious drug combinations that would not be selected based on complementary mechanisms can be identified via high-throughput screening.

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Patterns of platinum drug use in an acute care setting: a retrospective study

Abstract: The findings suggest that platinum drugs remain one of the most commonly dispensed drugs to treat cancer patients and most patients receive a dose reduction during treatment.

Cited by 23 publications

References 26 publications

Arsenoplatin-1 Is a Dual Pharmacophore Anticancer Agent

Arsenoplatin-1 Is a Dual Pharmacophore Anticancer Agent

Metal complexes for therapeutic applications

Screening-based approach to discover effective platinum-based chemotherapies for cancers with poor prognosis

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