Continuous infusion of low-dose doxorubicin, epirubicin and mitoxantrone in cancer chemotherapy: A review

Greidanus, J. W.; Willemse, Phb; Uges, Dra; Oremus, Ethgj; Delangen, Zj; Devries, Ege

doi:10.1007/bf02219662

Cited by 9 publications

(8 citation statements)

References 47 publications

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“…Anthraquinone-based drugs are used as chemotherapeutic agents 1, 2 and laxatives. 3 Moreover they show promise as treatments for malaria, 4, 5 and multiple sclerosis.…”

mentioning

confidence: 99%

Anthraquinone-2-sulfonic acid (AQ2S) is A Novel Neurotherapeutic Agent

2013

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Anthraquinone derivatives such as emodin have recently been shown to protect in models of beta amyloid β (Aβ) and tau aggregation-induced cell death. The mechanisms of action possibly involve preconditioning effects, anti-aggregation properties, and/or enhancing the phosphatidylinositol-3-kinase (PI3K)/AKT survival mechanism. We studied several natural (emodin, rhein, and aloin) and synthetic (AQ2S) anthraquinones, to screen for post-treatment therapeutic benefit in two models of neuronal death, namely hydrogen peroxide (H2O2) and staurosporine (STS)-induced injury. Treatment with emodin, rhein, or aloin failed to reduce H2O2 injury. Moreover, consistent with emodin behaving like a mild toxin, it exacerbated oxidative injury at the highest concentration used (50 μM) in our post-treatment paradigm, and potently inhibited AKT. In contrast, AQ2S was neuroprotective. It reduced H2O2 injury at 50 and 75 μM. In addition, AQ2S potently inhibited staurosporine (STS)-induced injury. The mechanisms of action involve caspase inhibition and AKT activation. However, blockade of AKT signaling with LY294002 failed to abolish AQ2S-mediated protection on the STS assay. This is the first study to report that AQ2S is a new neuroprotective compound and a novel caspase inhibitor.

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“…Anthraquinone-based drugs are used as chemotherapeutic agents 1, 2 and laxatives. 3 Moreover they show promise as treatments for malaria, 4, 5 and multiple sclerosis.…”

mentioning

confidence: 99%

Anthraquinone-2-sulfonic acid (AQ2S) is A Novel Neurotherapeutic Agent

2013

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“…The area under the curve (AUC) for leukocyte drug levels is higher during CI than the AUC observed following an equitoxic bolus of MTZ. 26,27 Few centres have undertaken pilot studies of CI-MTZ in relapsed and refractory patients with acute leukemia. 17,26 In patients with newly diagnosed acute lymphoblastic leukemia, the mode of administration of MTZ was shown to be equally effective, without significant difference in relapse rates or survival.…”

Section: Discussionmentioning

confidence: 99%

“…Previous reports on the continuous infusion of anthracyclines also suggest that this route of administration may be associated with less systemic toxicity compared to bolus therapy. 27,29 In phase I clinical studies of CI-MTZ conducted in patients with breast cancer, this mode of administration was associated with decreased myelotoxicity possibly due to avoidance of very high peak plasma levels, without a negative effect on disease response. 30,31 It is interesting to note that in the current study only one patient in the CI-MTZ group experienced a mild and reversible decrease in ejection fraction despite the repetitive use of CI-MTZ.…”

Section: Discussionmentioning

confidence: 99%

A randomized trial of continuous infusion versus bolus mitoxantrone in combination with cytarabine in newly diagnosed patients with acute myeloblastic leukemia

Koç

Oyan

Kars

et al. 2004

Hematological Oncology

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SUMMARYMitoxantrone (MTZ) has been shown to be effective in the treatment of newly diagnosed acute myeloblastic leukemia (AML). The objective of this randomized study was to evaluate the impact of mode of administration of MTZ on the response and recurrence rates in newly diagnosed patients with AML and to compare the toxicity patterns associated with bolus and continuous infusion (CI) of MTZ. From March 1987 to March 1994, 40 newly diagnosed patients with AML were randomized to receive either bolus or CI-MTZ, administered for 3 days at 10 mg/m 2 /day in combination with CI-cytarabine for 7 days at 100 mg/m 2 /day. Patients achieving complete remission (CR) received two consolidation cycles followed by monthly maintenance cycles, aiming a total of 12 cycles of chemotherapy. Fifteen patients (75%) in the bolus arm and 16 patients (80%) in the CI arm achieved CR. There were no significant differences in rates of early death and time to myeloid recovery between the two groups. After 11 years from the initiation of the study, median disease-free survival (DFS) in bolus and CI groups were 19 and 29 months after a median follow-up of 10 and 14 months, respectively. DFS rates at 10 years were 16.7% in the bolus group and 28.6% in the CI group ( p ¼ 0.36). Overall survival (OS) rates during the same period were 10.7 and 21.3% in the bolus and CI groups, respectively ( p ¼ 0.26). No relapse was observed in either group after 4 years. In patients younger than 40 years of age, DFS and OS were found to be significantly longer in the CI arm ( p ¼ 0.02 and p ¼ 0.03, respectively). Mild asymptomatic cardiotoxicity associated with a decrease of 10 to 20% in the ejection fraction occurred in a patient in CI-MTZ arm and in two patients in the bolus arm. None of these patients showed any evidence of cardiac failure during their subsequent follow-up. Grade III-IV alopecia ( p ¼ 0.05) and grade I-II hepatotoxicity ( p ¼ 0.01) were more frequent in the CI arm. A tendency for higher frequency of grade III-IV nausea was observed in the bolus arm (9 vs. 3%, p ¼ 0.10). As a conclusion, bolus and CI administration of MTZ were equally effective and tolerated well. Development of new anti-leukemia agents with novel treatment approaches is still needed to improve the high relapse rates in patients with AML who do not have an HLA-matched donor.

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“…Anthraquinone (AQ) derivatives constitute a large and diverse group, many of which have therapeutic properties and are used as chemotherapeutic, [1,2] antiviral, [3] immuneboosting [4] or anti-inflammatory agents. [5] They are considered as promising scaffolds for the development of antiviral drugs against SARS-CoV-2.…”

Section: Introductionmentioning

confidence: 99%

Adjusting the Structure of β-cyclodextrin to Improve Complexation of Anthraquinone-derived Drugs

Krzak¹,

Święch²,

Majdecki³

et al. 2021

Preprint

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β-cyclodextrin (CD) derivatives containing aromatic triazole ring were studied as potential carriers of drugs containing an anthraquinone moiety in the structure: anthraquinone-2-sulfonic acid (AQ2S), anthraquinone-2-carboxylic acid (AQ2CA) and a common anthracycline, daunorubicin (DNR). UV-Vis and voltammetry measurements were carried out to determine the solubilities and stability constants of the complexes formed and revealed the unique properties of the chosen CDs as effective pH dependent drug complexing agents. The stability constants of the drug complexes with the CDs containing triazole: βCDLip and βCDGAL were significantly larger than with the native βCD. The AQ2CA and AQ2S drugs are ill-soluble and their solubilities increased as the result of complex formation with βCDLip and βCDGAL ligands. AQ2CA, AQ2S were negatively charged at pH 7.4 and therefore they were less prone to form inclusion complex with the hydrophobic CD cavity than at pH 3 (characteristic of gastric juices) when they were protonated. βCDTriazole and βCDGAL ligands were found to form weaker inclusion complexes with the positively charged drug DNR at acidic pH (pH 5.5) than in the neutral medium (pH 7.4) when the drug dissociates to the neutral, uncharged form. This pH dependence is favorable for anti-tumor applications.

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Continuous infusion of low-dose doxorubicin, epirubicin and mitoxantrone in cancer chemotherapy: A review

Cited by 9 publications

References 47 publications

Anthraquinone-2-sulfonic acid (AQ2S) is A Novel Neurotherapeutic Agent

Anthraquinone-2-sulfonic acid (AQ2S) is A Novel Neurotherapeutic Agent

A randomized trial of continuous infusion versus bolus mitoxantrone in combination with cytarabine in newly diagnosed patients with acute myeloblastic leukemia

Adjusting the Structure of β-cyclodextrin to Improve Complexation of Anthraquinone-derived Drugs

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