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| LETTER TO EDITOR |
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| Year : 2020 | Volume
: 3
| Issue : 2 | Page : 394-395 |
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Metronomics: The next generation of multitargeted therapy
Shripad Banavali, Vijay Patil, Vanita Noronha, Kumar Prabhash
Department of Medical Oncology, Tata Memorial Centre; Homi Bhabha National Institute, Mumbai, Maharashtra, India
| Date of Submission | 31-Mar-2020 |
| Date of Decision | 01-Apr-2020 |
| Date of Acceptance | 02-Apr-2020 |
| Date of Web Publication | 19-Jun-2020 |
Correspondence Address:
Shripad Banavali
MD Director Academics Tata Memorial Centre, Mumbai, Maharashtra
India
 Source of Support: None, Conflict of Interest: None
DOI: 10.4103/CRST.CRST_106_20
How to cite this article:
Banavali S, Patil V, Noronha V, Prabhash K. Metronomics: The next generation of multitargeted therapy. Cancer Res Stat Treat 2020;3:394-5 |
We were delighted to read the article titled, “Oral etoposide and cyclophosphamide: A low-cost Palliative Metronomic Chemotherapy in advanced pediatric cancers” by Kumar et al.[1] and the accompanying editorial.[2] This study comprised a retrospective collection of data from 49 patients treated over a period of time with metronomic chemotherapy and has its limitations in the form of a heterogeneous treatment population and variable treatment schedules. Having obtained a median overall survival of 155 days with low toxicity, the authors have concluded that a combination of oral cyclophosphamide and etoposide is a convenient and economical regimen with acceptable response rates in the palliative setting. This is yet another article in the slowly increasing literature on the use of oral metronomic therapies (OMTs) for pediatric cancers.[3],[4]
However, as pointed out by us previously,[5] the regimen does not actually fit into the category of OMTs. By definition, metronomic therapy is “long-term administration of chemotherapeutic agents in a relatively low, minimally toxic dose, with no prolonged drug-free breaks.”[5] As reported in the paper, nearly half of the patients received drugs for 2 weeks with 2 weeks off. This means that the patients received no drugs for 50% of the time, which is a prolonged drug-free break. Furthermore, another limitation of this study is that the authors have clubbed all the tumors together. In this era of precision medicine, we know that the hallmarks of cancer as well as the pathways involved are different not only for different types of cancers, but also for their subtypes. Therefore, one would ideally require different combinations of OMTs for different tumors.[6]
A vital piece of information that this paper provides is that metronomic therapies can not only be useful in solid tumors, but also in hematological malignancies. One of the most successful treatments in oncology is the treatment of childhood acute lymphoblastic leukemia, which is a prime example of metronomic therapy, especially with the standard-risk and intermediate-risk protocols. Therefore, as Dr. Amegan-Aho mentions, we are not only “surviving on less,” we are thriving on less.[2]
With accumulating data, we have moved forward by combining metronomic chemotherapy with repurposed drugs labeled as “metronomics.”[6],[7] We have successfully repurposed drugs such as celecoxib, propranolol, metformin, and tamoxifen. An ideal and effective metronomic combination should have drugs that act on the tumor, drugs that modify the tumor microenvironment, and drugs that modulate immunity. Thus, “metronomics” can potentially become the next generation multi-targeted therapy. Recently, we have published that when used in the right combination, OMCTs can be very effective in patients with refractory/relapsed sarcomas.[8]
We conclude with a quote from Victor Hugo– “Nothing else in the world, not all the armies ……is so powerful as an idea whose time has come.” Now is the right time to conduct randomized, multicentric trials in this field and find out how best to use these cost-effective and infrastructure-sensitive therapies to our advantage.[9] Many of us must have used metronomic therapies during this crisis of the COVID-19 pandemic.[10],[11] Perhaps, collating and publishing these data would be a good start!
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
| References | |  |
| 1. | Kumar K, Radhakrishnan V, Dhanushkodi M, Kalaiyarasi JP, 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.  [Full text] |
| 2. | Amegan-Aho KH. Surviving on less. Cancer Res Stat Treat 2020;3:87-8. [Full text] |
| 3. | Bhuvan LP, Radhakrishnan V, Raja A, Ganesarajah S, Sagar TG. Outcomes in rhabdomyosarcoma: Experience from a tertiary cancer center in India. Cancer Res Stat Treat 2019;2:4-9. |
| 4. | Parambil BC, Ramanathan S. Improving outcomes in rhabdomyosarcoma – The way ahead. Cancer Res Stat Treat 2019;2:69-71. [Full text] |
| 5. | Banavali S, Prabhash K, Patil V. Assessing metronomic chemotherapy for progressive pediatric solid malignant tumors. JAMA Oncol 2018;4:743-4. |
| 6. | André N, Banavali S, Snihur Y, Pasquier E. Time for metronomics in developing countries? Lancet Oncol 2013;14:e239-48. |
| 7. | Chandrasekharan A, Karunanithi S, Gangadharan KV. Metronomic chemotherapy and propranolol in a patient with metastatic angiosarcoma: Magic bullets? Cancer Res Stat Treat 2020;3:110-2. [Full text] |
| 8. | Devadas SK, Banavali S. Retrospective analysis of outcomes of patients with relapsed, refractory and metastatic sarcomas who have received metronomic chemotherapy. Gulf J Oncol 2019;1:22-8. |
| 9. | Noronha V. Making a case for cancer research in India. Cancer Res Stat Treat 2018;1:71-4. [Full text] |
| 10. | Saroha M, Moulik NR. COPING with CORONA: A developing country perspective on managing children with cancer during COVID-19 pandemic. Cancer Res Stat Treat 2020;3 Suppl S1:97-101. |
| 11. | Patil VM, Srikanth A, Noronha V, Joshi A, Dhumal S, Menon N, et al. The pattern of care in head-and-neck cancer: Comparison between before and during the COVID-19 pandemic. Cancer Res Stat Treat 2020;3 Suppl S1:7-12. |
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