Authors’ response to “Evaluation of Treatments for HIV-Associated Kaposi Sarcoma in Africa”,Infectious Agents and Cancer

当前位置： X-MOL 学术 › Infect. Agents Cancer › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Authors’ response to “Evaluation of Treatments for HIV-Associated Kaposi Sarcoma in Africa”
Infectious Agents and Cancer ( IF 3.1 ) Pub Date : 2021-05-05 , DOI: 10.1186/s13027-021-00372-5
Matthew E. Coldiron , Ana Gabriela Gutierrez Zamudio , Rolanda Manuel , Iza Ciglenecki , Laurence Toutous Trellu , Lucas Molfino

We thank Drs Krown and Borok for the interest they have shown in our work and the opportunity they give us to draw attention to the extremely poor access to cancer treatment in resource-limited settings. Nonetheless, we feel it is important to clarify certain points.

Most importantly, safety follow-up of participants in our study was extensive. In addition to blood counts, serum creatinine and ALT were monitored before each PLD infusion, and PLD was held in case of abnormalities (as stated in the method section of the manuscript) [1]. Furthermore, the presence of AEs was assessed at each study visit, including at the regular PLD infusions. The type and severity of non-serious AE are described in the manuscript.

We agree with several of their concerns about the limitations of our single-site observational study, many of which we presented in the discussion of our manuscript. Our loss to follow-up (13 %) was indeed higher than in the clinical trial co-chaired by Drs Krown and Borok (though our follow up was 24 months vs. 48 weeks in the trial), but our study was not a clinical trial, and loss to follow up over the study period was much lower than in a historical cohort at the same center (36 %) [2, 3].

We used standard outcome measures used in multiple previous studies and believe that this was prudent given the single-site, observational nature of our study. We also point out that the duration of response was defined.

Importantly, we underscore that the study and all patient care provided at the study site (including HIV, TB and KS care) is a result of close collaboration and priority-setting between MSF and the Mozambican Ministry of Health.

Overall, we have not attempted to overstate our results and, as discussed in our manuscript, we believe that direct comparisons of PLD and paclitaxel are necessary. Yet, given the length of time it takes to set up and run such trials, we believe it is imperative to continue improving patient care now. The treatment gap for cancer patients in most of sub-Saharan Africa is a chasm. MSF is often a provider of last resort in these environments, with no viable chemotherapy alternatives available for KS or any other cancer.

Despite the limitations of our observational study, documenting our experience with PLD helped fill important information gaps for the Ministry of Health in Mozambique, led to changes in the national treatment protocol, and to financing for PLD by the Global Fund. PLD is a better solution for patients with advanced KS than the traditional ABV regimen, particularly in ambulatory settings, which is crucial for scale-up of cancer treatment. While waiting for results of direct comparisons between PLD and paclitaxel, which we welcome, this is a pragmatic step forward. Certainly, given its extensive use in high-income settings, PLD’s expansion into low-income settings like Mozambique is welcome. We hope other countries in resource-limited settings will follow Mozambique’s example and provide access to chemotherapy for patients with KS and other cancers.

Not applicable

ALT:: Alanine aminotransferase
PLD:: Pegylated liposomal doxorubicin
AE:: Adverse event
HIV:: Human immunodeficiency virus
KS:: Kaposi sarcoma
MSF:: Médecins Sans Frontières (Doctors Without Borders)
ABV:: Combination therapy with doxorubicin, bleomycin and vincristine

1.
Coldiron ME, Gutierrez Zamudio AG, Manuel R, Luciano G, Rusch B, Ciglenecki I, et al. Outcomes of AIDS-associated Kaposi sarcoma in Mozambique after treatment with pegylated liposomal doxorubicin. Infect Agent Cancer. 2021;16:2
2.
Krown SE, Moser CB, Macphail P, Matining RM, Godfrey C, Caruso SR, et al. Treatment of advanced AIDS-associated Kaposi sarcoma in resource-limited settings: a three-arm, open-label, randomised, non-inferiority trial. Lancet. 2020;395:1195–207.
CAS Article Google Scholar
3.
Fardhdiani V, Molfino L, Zamudio AG, Manuel R, Luciano G, Ciglenecki I, et al. HIV-associated Kaposi’s sarcoma in Maputo, Mozambique: Outcomes in a specialized treatment center, 2010–2015. Infect Agent Cancer. 2018;13:5.

Download references

None

Médecins Sans Frontières.

Affiliations

Epicentre, 14-34 Avenue Jean Jaurès, 75019, Paris, France
Matthew E. Coldiron
Médecins Sans Frontières, Maputo, Mozambique
Ana Gabriela Gutierrez Zamudio & Lucas Molfino
Ministry of Health, Maputo, Mozambique
Rolanda Manuel
Médecins Sans Frontières, Geneva, Switzerland
Iza Ciglenecki
University Hospitals of Geneva, Geneva, Switzerland
Laurence Toutous Trellu

Authors

Matthew E. ColdironView author publications
You can also search for this author in PubMed Google Scholar
Ana Gabriela Gutierrez ZamudioView author publications
You can also search for this author in PubMed Google Scholar
Rolanda ManuelView author publications
You can also search for this author in PubMed Google Scholar
Iza CigleneckiView author publications
You can also search for this author in PubMed Google Scholar
Laurence Toutous TrelluView author publications
You can also search for this author in PubMed Google Scholar
Lucas MolfinoView author publications
You can also search for this author in PubMed Google Scholar

Contributions

MEC wrote the first draft of the response. All authors made important intellectual contributions to the work and have agreed the final draft for submission.

Corresponding author

Correspondence to Matthew E. Coldiron.

Ethics approval and consent to participate

Not applicable

Consent for publication

Not applicable

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and Permissions

Cite this article

Coldiron, M.E., Gutierrez Zamudio, A.G., Manuel, R. et al. Authors’ response to “Evaluation of Treatments for HIV-Associated Kaposi Sarcoma in Africa”. Infect Agents Cancer 16, 27 (2021). https://doi.org/10.1186/s13027-021-00372-5

Download citation

Received: 23 April 2021
Accepted: 29 April 2021
Published: 05 May 2021
DOI: https://doi.org/10.1186/s13027-021-00372-5

Keywords

Kaposi sarcoma
Acquired Immunodeficiency Syndrome
Mozambique
AIDS-related opportunistic infections
Doxorubicin

中文翻译：

作者对“非洲与艾滋病相关的卡波济肉瘤的治疗评估”的回应

我们感谢Krown博士和Borok博士对我们的工作表现出的兴趣，以及他们给我们提供的机会来提请我们注意在资源有限的环境中极难获得癌症治疗的机会。尽管如此，我们认为澄清某些要点很重要。

最重要的是，我们研究参与者的安全性随访很广泛。除血液计数外，每次PLD输注前还应监测血清肌酐和ALT，并在异常情况下保持PLD（如方法部分所述）[1]。此外，在每次研究访视时（包括在常规PLD输注时）都评估了AE的存在。非严重不良事件的类型和严重程度在手稿中进行了描述。

我们同意他们对我们单点观察研究的局限性的担忧，我们在讨论稿件时提出了许多担忧。我们的随访损失（13％）确实比Krown和Borok博士共同主持的临床试验要高（尽管我们的随访时间是24个月，而试验是48周），但是我们的研究不是临床的研究期间，随访期间的随访损失远低于同一中心的历史队列（36％）[2，3]。

我们使用了多项先前研究中使用的标准结局指标，并认为鉴于我们研究的单点观察性质，这是审慎的做法。我们还指出，响应的持续时间已定义。

重要的是，我们强调该研究和研究现场提供的所有患者护理（包括HIV，TB和KS护理）是无国界医生与莫桑比克卫生部之间密切合作和确定优先重点的结果。

总的来说，我们没有试图夸大我们的结果，并且，正如我们在手稿中所讨论的，我们认为PLD和紫杉醇的直接比较是必要的。但是，考虑到建立和运行此类试验所需的时间，我们认为现在必须继续改善患者护理。在撒哈拉以南非洲大部分地区，癌症患者的治疗差距是一个鸿沟。在这些环境中，无国界医生通常是万不得已的提供者，对于KS或任何其他癌症，没有可行的化学疗法可供选择。

尽管我们的观察性研究存在局限性，但记录我们在PLD方面的经验仍有助于填补莫桑比克卫生部的重要信息空白，导致国民治疗方案的变化以及全球基金为PLD筹集资金。与传统的ABV方案相比，PLD是晚期KS患者更好的解决方案，特别是在非卧床环境中，这对于扩大癌症治疗至关重要。在等待我们欢迎PLD和紫杉醇之间直接比较的结果时，这是一个务实的进步。当然，考虑到它在高收入环境中的广泛使用，PLD扩展到莫桑比克等低收入环境受到欢迎。我们希望资源有限的其他国家能效仿莫桑比克的做法，为患有KS和其他癌症的患者提供化学疗法的途径。

不适用

ALT：: 丙氨酸氨基转移酶
PLD：: 聚乙二醇脂质体阿霉素
AE：: 不良事件
艾滋病病毒：: 人类免疫缺陷病毒
KS：: 卡波济肉瘤
无国界医生：: 无国界医生（无国界医生）
ABV：: 阿霉素，博来霉素和长春新碱的联合治疗

1。
Coldiron ME，Gutierrez Zamudio AG，Manuel R，Luciano G，Rusch B，Ciglenecki I等。用聚乙二醇化脂质体阿霉素治疗后，莫桑比克与艾滋病相关的卡波西肉瘤的结果。感染剂癌症。2021; 16：2
2。
Krown SE，Moser CB，Macphail P，Matining RM，Godfrey C，Caruso SR等。在资源有限的环境中治疗晚期艾滋病相关的卡波济肉瘤：一项三臂，开放标签，随机，非自卑性试验。柳叶刀。2020; 395：1195–207。
CAS文章Google学术搜索
3。
Fardhdiani V，Molfino L，Zamudio AG，Manuel R，Luciano G，Ciglenecki I等人。莫桑比克马普托的艾滋病毒相关的卡波济肉瘤：2010-2015年在专门治疗中心的结局。感染剂癌症。2018; 13：5。

下载参考

没有任何

无国界医生组织。

隶属关系

Epicentre，JeanJaurès大道14-34号，75019，巴黎，法国
马修·柯迪伦（Matthew E. Coldiron）
莫桑比克马普托无国界医生组织
安娜·加布里埃拉·古铁雷斯·萨穆迪奥和卢卡斯·莫尔菲诺
莫桑比克马普托卫生部
罗兰达·曼努埃尔（Rolanda Manuel）
无国界医生，瑞士日内瓦
伊萨·西格列内基（Iza Ciglenecki）
日内瓦大学医院，瑞士日内瓦
劳伦斯·图图斯·特雷卢（Laurence Toutous Trellu）

作者

Matthew E. Coldiron查看作者出版物
您也可以在PubMed Google学术搜索中搜索该作者
Ana Gabriela Gutierrez Zamudio查看作者出版物
您也可以在PubMed Google学术搜索中搜索该作者
罗兰达·曼努埃尔（Rolanda Manuel）查看作者出版物
您也可以在PubMed Google学术搜索中搜索该作者
Iza Ciglenecki查看作者出版物
您也可以在PubMed Google学术搜索中搜索该作者
劳伦斯·图图斯·特雷卢（Laurence Toutous Trellu）查看作者出版物
您也可以在PubMed Google学术搜索中搜索该作者
卢卡斯·莫尔菲诺（Lucas Molfino）查看作者出版物
您也可以在PubMed Google学术搜索中搜索该作者

会费

MEC撰写了回应的初稿。所有作者都为这项工作做出了重要的智力贡献，并同意了最终稿以供提交。

通讯作者

对应于Matthew E. Coldiron。

道德规范的批准和参与同意

不适用

同意发表

不适用

利益争夺

作者宣称他们没有竞争利益。

发行人的便条

对于已发布地图和机构隶属关系中的管辖权主张，Springer Nature保持中立。

开放存取本文是根据知识共享署名4.0国际许可许可的，该许可允许以任何媒介或格式使用，共享，改编，分发和复制，只要您对原始作者和出处提供适当的信誉，即可提供链接到知识共享许可，并指出是否进行了更改。本文的图像或其他第三方材料包含在该文章的知识共享许可中，除非在该材料的信用额度中另有说明。如果该材料未包含在该文章的创用CC许可中，并且您的预期用途未得到法律法规的许可或超出了许可的用途，则您将需要直接从版权所有者那里获得许可。要查看此许可证的副本，请访问http://creativecommons.org/licenses/by/4.0/。

转载和许可