Talk:WikiJournal of Medicine/Anthracyclines

Latest comment: 6 years ago by Alisoncheong in topic Second peer review

WikiJournal of Medicine
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<meta name='citation_doi' value='10.15347/wjm/2018.001'>

Article information

Authors: Alison Cheong[i][a], Sean McGrath[i][a], Suzanne Cutts[a][ii]  

See author information ▼
  1. 1.0 1.1 1.2 La Trobe University, Melbourne, Australia
  1. 1.0 1.1 contributed equally to the work
  2. s.cutts@latrobe.edu.au

 

Plagiarism check

  Pass. Report from WMF copyvios tool: Violation Unlikely, 5.7% confidence. Matches were "...for the treatment of cancer" and "...anthracyclines are doxorubicin, daunorubicin, epirubicin and idarubicin" that matches text from the following work:

  • McGowan, John V; Chung, Robin; Maulik, Angshuman; Piotrowska, Izabela; Walker, J Malcolm; Yellon, Derek M (2017). "Anthracycline Chemotherapy and Cardiotoxicity". Cardiovascular Drugs and Therapy 31 (1): 63–75. doi:10.1007/s10557-016-6711-0. ISSN 0920-3206. 

However, the former is a common phrase, and the latter is just a particular ordering of main members, so neither is significant plagiarism. Mikael Häggström (discusscontribs) 19:49, 19 April 2018 (UTC)Reply

Agreed; no problem here. Klbrain (discusscontribs) 16:31, 2 May 2018 (UTC)Reply

Editor's comment


Comments by anonymous editor ,
These editorial comments were submitted on , and refer to this previous version of the article

The article reads well with an appropriate scientific style and is appropriately referenced. I've added some wikilinks; it's suitable for review.

First peer review


Review by anonymous peer reviewer , Lecturer at a UK University
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These assessment comments were submitted on , and refer to this previous version of the article

Overall a nice section about anthracylines liposomal based formulations that needs few amendments and additions as highlighted below:

In regards to the section on liposomal-based clinical formulations, I would include a small paragraph about what are liposomes and their use as drug delivery systems (DDS). A structure or schematic of a conventional liposome should also be included as well as where the anthracyclines are included within the liposome.

Response

As an introduction to this section we have now added a short description of liposomes and their use as a drug delivery system, with a link to a description of liposomes. We have also added an original figure of basic liposome structure with encapsulated doxorubicin (Figure 3A), as well as an electron micrograph of doxil liposomes (Figure 3B).

Please change the word “nano-drug” to liposomal drug delivery system (DDS) as the drug is the same but was just encapsulated inside a liposome.

Response

The term “nano-drug” has been removed and replaced with the suggested description (3rd para, 1st sentence).

No need to mention “weakly anionic”, just keep hydrophilic polyethylene glycol polymer (PEG)

Response

We have removed the description “weakly anionic” (3rd para, 2nd sentence)

There is no link of the PEG to the retention/encapsulation of doxorubicin inside the liposomes as stated in this sentence “The PEG coating serves as a barrier from opsonisation, rapid clearance and stably retains the drug inside the nano-carriers via an ammonium sulphate chemical gradient”. The chemical gradient is independent on the PEG coating, please refer to this reference Haran et al. Biochim. Biophys. Acta. 1993;1151:201–215.

Response

We have corrected the sentence and added the suggested reference (3rd para, 3rd sentence).

I am not sure what “these characteristics” refer to in the 2nd paragraph. For clarifications, while the PEGylation prolongs the circulation of the liposomes, the improvement in tumour targeting is indirectly related to the improved circulation but also due to the size of the liposomes via the enhanced permeability and retention (EPR) effect which is not equal to extravasation through the leaky vasculature as the authors had between brackets. EPR effect = passive targeting which takes advantage of the leaky vasculature, size of DDS and prolonged retention due to impaired lymphatic drainage etc. Authors can refer this review Maeda et al 2013, Advanced Drug Delivery Reviews, 65(1)71-19 and reference it in their article.

Response

We have modified the text to more accurately describe the EPR effect and have added the suggested reference (3rd para, 4th sentence).

What do you mean by free drug peak? Maximum serum concentration that doxorubicin achieve after Doxil administration ? Please add respectively after this sentence “Doxil can cause Palmar-plantar erythrodysesthesia (PPE, hand and foot syndrome) and mucositis due to its accumulation in the skin and mucous respectively” though I am not sure how significant and common is mucositis.

Response

For clarification, we have changed the term “free drug peak” to “maximum plasma concentration of free doxorubicin”. We have removed the mention of mucositis and just retained the mention of PPE as this is the major adverse effect (4th para).

Authors need to add how different LipoDox is in terms of pharmacokinetics and side effects to Doxil.

Response

LipoDox is the generic version of Doxil and has not been well studied so we have chosen to remove this small section.

DaunoXome is [discontinued by the FDA] so I would remove that section as you are highlighting the anthracycline liposomal-based clinical formulations.

Response

As suggested, we have removed this section.

As for Myocet, authors need to mention its half-life and how comparable is it to that of Doxil. The diameter of the liposomes as this was mentioned for Doxil. It should also be mentioned that the loading of Doxorubicin in Myocet is based on a pH gradient. Why isPPE rare in Myocet treated patients. Any other significant side effects?

Response

Myocet and Doxil have now been compared in a new Table (Table 3). We have removed the statement of Mycocet with respect to PPE.

I recommend that the authors include a table in which they compare the clinically approved anthracycline liposomal formulation in a similar attempt to what they have included in the following section “Clinical Trials” and they should include:

  • Composition of liposome including PEGylation
  • Size of the liposomes
  • How the doxorubicin is loaded inside the liposomes (concentration or pH gradient)
  • Dose, volume of distribution and half- life in comparison to doxorubicin alone
  • Clinical indication
Response

A new Table (Table 3) has been added to incorporate this information.

In regards to the section on Clinical Trials, the authors are advised to make sure their table is up-to-date and to check whether these systems are currently in clinical trials or they were as some of the references that were used are from 2011/2014. It will also be good if the authors include the status of the clinical trial (recruiting, completed etc).

Response

The table has been updated (Table 4). Specifically we have updated the current status, added clinical trial links, and we have removed the nano-carrier candidates that have been discontinued.

Conflict of interest : none declared


Comments by anonymous editor ,
These editorial comments were submitted on , and refer to this previous version of the article

Reviewer 1 has informed me that "I am happy with the revision and how that section looks like now"

Second peer review


Review by anonymous peer reviewer , Chemistry and chemical Engineering lecturer
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These assessment comments were submitted on , and refer to this previous version of the article

Few lines are not clearly elaborated in abstract like Several liposomal formulations of are in use....of what?

Response

We have corrected the sentence to indicate that several liposomal formulations of doxorubicin are in use, and rectified minor errors. Alisoncheong (discusscontribs) 03:14, 21 November 2018 (UTC)Reply

In history, author claimed that thousands of analogues have been produced ........ therapeutic applications. Briefly explain about analogues and their positive or negative aspects.

Response

We have added extra detail about the advantage of the clinically used anthracycline analogue idarubicin as it is orally bioavailable. We have also added a paragraph describing other useful compounds to stem from the anthracyclines, including the clinically used anthracenedione drug mitoxantrone. Alisoncheong (discusscontribs) 04:17, 27 November 2018 (UTC)Reply

In my point of view, the mechanism of action need to be explain in more details.

Response

We have focused on mechanisms that have been characterised to be relevant at clinically achievable drug doses, and also provided an introductory paragraph to provide context for this section. Furthermore we have added a section describing the use of biomarkers that have been evaluated to be predictive of anthracycline benefit in breast cancer patients. Alisoncheong (discusscontribs) 04:17, 27 November 2018 (UTC)Reply

Overall article is good, but author should also include section about anthracyclines as radiopharmaceutical.

Response

Radiopharmaceutical versions of anthracyclines are not currently used in the clinic. However, a promising technetium-labelled version of doxorubicin for tumour imaging has been reported in the literature and this has now been described. Alisoncheong (discusscontribs) 04:17, 27 November 2018 (UTC)Reply

Conflict of interest : none declared


Comments by anonymous editor ,
These editorial comments were submitted on , and refer to this previous version of the article

Reviewer 2 has informed me that " Yes, authors address all the point which I recommended. I am satisfy with the author response. I think no further update is needed for this article."

Editor's summary


Comments by anonymous editor ,
These editorial comments were submitted on , and refer to this previous version of the article

My view is that the article is genuinely strong and written by subject experts. I’d be happy to see it published with only 2 reviews. The editors have made some good points which the authors have appropriately responded to; both reviewers have confirmed that they are satisfied with the responses.

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