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Table of Contents
EDITORIAL
Year : 2020  |  Volume : 3  |  Issue : 1  |  Page : 87-88

Surviving on less


Department of Paediatrics, University of Health and Allied Sciences, Ho, Volta Region, Ghana

Date of Submission03-Jan-2020
Date of Decision13-Jan-2020
Date of Acceptance18-Jan-2020
Date of Web Publication24-Feb-2020

Correspondence Address:
Kokou Hefoume Amegan-Aho
PMB 31, Ho, Volta Region
Ghana
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_4_20

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How to cite this article:
Amegan-Aho KH. Surviving on less. Cancer Res Stat Treat 2020;3:87-8

How to cite this URL:
Amegan-Aho KH. Surviving on less. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Apr 10];3:87-8. Available from: http://www.crstonline.com/text.asp?2020/3/1/87/279114



The high survival rates of more than 80% achieved in childhood cancer treatment have been based on intensive therapy or maximum tolerated dose. With the refinement in risk stratification, groups of patients that can achieve acceptably high survival with less intensive therapy and therefore less treatment related toxicity are being identified.[1] Consequently, it becomes logical to assume that smaller doses of anticancer agents are all that is needed in some patients. This approach is quite tempting in resource-constrained lower-middle income countries (LMCs) which carry the huge burden of cancer cases, but limited by the fact that long-term survival rarely exceeds 20% in some of these countries.[2] The reasons for the dismal outcome in the LMC are many. A significant number of patients are diagnosed at an advanced stage and therefore are likely to relapse or qualify for outright palliative care. The limited supportive care available in the LMCs means that treatment toxicities cannot be managed efficiently. In addition, most families do not have enough resources to absorb the huge costs of treatment.[3] Parents/patients' lack of faith in the health-care system due to high mortality rate may fuel delay in diagnosis and treatment abandonment, creating a vicious circle.[4]

Giving low-dose chemotherapy in a continuous fashion without prolonged drug-free breaks, as in the case of oral metronomic chemotherapies (OMC),[5] may well suit the reality of the LMC.[6] Among the mechanism of actions of OMC such as the activation of immunity,[5] induction of tumor dormancy, and senescence,[7] their antiangiogenic properties are probably the most studied.[8] Endothelial cells that contribute to tumor growth are more susceptible to low-dose chemotherapy without significant possibility of developing resistance.[9] In addition, certain agents at low dose, such as cyclophosphamide, can still kill tumor cell directly.[10] Through regular symposia such as that organized in Mumbai in 2016,[11] the question of OMC has gathered enough momentum. Evidence is needed especially in LMC to advance therapy and improve survival. While numerous studies on OMC are conducted in the adult population, evidence in pediatric malignancies is scanty.

In this retrospective study covering a 7-year period, Kumar et al.[12] present the real-world evidence of 49 children aged between 1 and 18 years with relapsed/refractory childhood cancers. There were 14 cases of hematolymphoid malignancies (non-Hodgkin lymphoma [HL], HL, and acute myeloid leukemia [AML]) and 25 cases of solid tumors (Ewing's sarcoma, osteosarcoma, neuroblastoma, and rhabdomyosarcoma) treated nonuniformly with various doses and schedules of 2-drug OMC (cyclophosphamide and etoposide). After a median treatment period of 50 days, there was no evidence of complete tumor response in any case. However, 11 (22.4%) patients showed some clinical benefit in terms of partial response (10.2%) or stable disease (12.2%). Based on the specific malignancy, clinical benefit was noted in about one-third of the patients with HL and Ewing's sarcoma. No clinical benefit was noted in the four patients with osteosarcoma. There was stable disease in one out of the four patients with AML. The median time to progression and death was about 2 months and 5 months, respectively. The authors reported that lower age and longer duration of treatment were independent predictors of higher OS, but the details were not available.[12]

The retrospective design, the limited number of cases, and the heterogeneous treatment regimens are the major limitations of this study. There were no data on the number of conventional treatments with curative intent given to the patients before relapse to inform future analysis on the impact of the chemo-switch phenomenon[13] on outcome. Although this was a retrospective study, comparison to a control group such as patients on palliation without chemotherapy or any other antiangiogenic drug would have been very informative.

This study contributes to evidence on the impact of OMC in improving survival after conventional therapies have failed or if they cannot be given upfront. The clinical benefit rate in Ewing's sarcoma is particularly encouraging. This contrasts with the results of the randomized controlled trial by Pramanik et al., which did not show any benefit of a 4-drug OMC in bone tumors.[14] The study by Kumar et al. also sheds some light on the usefulness of OMC in pediatric hematolymphoid malignancies. The toxicity rate associated with OMC in this study is acceptable. OMC indeed presents an opportunity for limited resource centers in prolonging or improving the quality of life when the goal of treatment is no longer curative but palliative. With the ongoing advances in research and with the encouraging results using targeted therapies, there is a hope that OMC would be indicated upfront in more patients, with acceptable outcomes, especially in patients at high risk of relapse after completion of conventional treatment.[15]

Clinical trials using different regimens of OMC in LMC are needed.[16] The role of OMC in pediatric hematolymphoid malignancies, the reasons why some types of patients do not respond to OMC and the use of concomitant traditional treatment among patients on palliative therapy need to be clarified. Centers with limited resources should consider homogeneous regimens and schedules of OMC either upfront in patients with advanced pediatric cancers or as alternative treatment when conventional therapy has failed.



 
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Kumar K, Radhakrishnan V, Dhanushkodi M, Jeyachandran PK, Mehra N, Kumar AR, et al. Oral etoposide and cyclophosphamide: A low-cost palliative metronomic chemotherapy in advanced pediatric cancers. Cancer Res Stat Treat 2020;3:64-8.  Back to cited text no. 12
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Chinnaswamy G, Sankaran H, Bhat V, KC A, Saroha M, Prasad M, et al. Dev-19. The role of combat (combined oral metronomic biodifferentiating antiangiogenic treatment) in high-risk and relapsed medulloblastoma: A single institution experience. Neuro Oncol 2018;20 Suppl 2:i48-9.  Back to cited text no. 15
    
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Noronha V. Making a case for cancer research in India. Cancer Res Stat Treat 2018;1:71-4.  Back to cited text no. 16
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