|LETTER TO EDITOR
|Year : 2020 | Volume
| Issue : 1 | Page : 131-133
Authors' reply to Kumar et al. and Kannan et al.
Vijai Simha, Vijay Patil, Amit Joshi, Kumar Prabhash, Vanita Noronha
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India
|Date of Submission||23-Jan-2020|
|Date of Acceptance||24-Jan-2020|
|Date of Web Publication||24-Feb-2020|
Department of Medical Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Simha V, Patil V, Joshi A, Prabhash K, Noronha V. Authors' reply to Kumar et al. and Kannan et al. Cancer Res Stat Treat 2020;3:131-3
We thank the authors for their valuable comments regarding our review article on systemic therapy for esophageal and gastroesophageal cancer.
The fact that systemic therapy has shown a survival benefit in the meta-analysis notwithstanding the small magnitude itself shows that there is a general favorable signal with the use of these agents in advanced esophageal cancer. The survival benefit is small, and the risk-benefit analysis is not clear; we completely agree with Kumar and Shetty that more robust evidence is needed.
Palliative chemotherapy can improve dysphagia and improve quality of life apart from the impact on survival as pointed out in an article by Joshi et al. The purpose of the review article was to put in front of the readers an unbiased review of all the relevant work that has been done recently as well as the past and does not necessarily imply that aggressive systemic therapies must be utilized in each and every patient.
We hope to drive away the attitude of therapeutic nihilism that has originated from years together of toxic and unsuccessful intravenous chemotherapy. Chemotherapies in the 1990s meant high dose of chemotherapy and an immediate threat from mortality due to the treatment., The results from these studies were so disappointing that the doors of systemic therapy appeared to have been shut forever for any patient with advanced esophageal cancer. However, with the advent of targeted therapy, metronomic therapy (particularly oral metronomic therapy), systemic therapy can be gentle yet effective.,, These studies showed that a small proportion of patients (who represent the tails of the Kaplan–Meier curves) benefit more than the average patient exposed to such systemic therapies. The identification of this population would be the goal of treating physicians. Careful selection and mindfulness of toxicities in all patients will lead to early dose modification or stoppage of futile therapies in nonresponders while continuing the same therapies in responders.
While evidence may be generated from trials with fit patients in ideal settings, it is the duty of the practitioner relying on these trials to apply the results of these trials to similar patients in practice. Systemic therapy should not be used without regard to performance status, comorbidities, and organ function. Patients with advanced esophageal cancer may occasionally have an excellent performance status and these patients may benefit from two drugs or even three-drug combinations.
Kannan and Rangarajan make a very important point that histology is an important differentiator in the management of esophageal carcinoma. In our article, we have not overtly mentioned that certain regimens may not be appropriate for squamous cell carcinomas, but we have mentioned whether a particular trial only included patients with adenocarcinoma histology.
We disagree with the statement that recent studies have only focused on adenocarcinomas, as recent trials, including the immunotherapy trial KEYNOTE-181 stratified patients based on histology. Similarly, trials evaluating cetuximab in esophageal carcinoma and the metronomic studies also included squamous cell histologies. We have structured our article based on the type of agents rather than histologies and hence the use of the regimen with regard to the histology may not be clearly evident in the flow of the article as the authors have pointed out.
We agree with Kumar et al.'s comments on the cost implications of the regulatory approval of drugs which have a small clinical benefit. Our literature review suggests that very inexpensive drugs can be used in such complex situations so that patients from all walks of life stand to benefit from low dose systemic therapies rather than end up at the proverbial 'table in the corner.' While the ESMO Magnitude of Clinical Benefit Scale may be useful in making policy decisions, it may not mean much at an individual level. Balancing the quantum of benefit with quality of life is very important when using any therapy.
Despite significant advances in other cancer sites, esophageal cancer continues to be ever evasive to medical breakthroughs though progress is occurring at a very slow pace and definitely in a positive direction. Discovery of new molecular targets or druggable mutations may be perhaps the only hope for this disease, which continues to bear a tag of 'dismal disease.'
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Simha V, Patil V, Joshi A, Prabhash K, Noronha V. Role of palliative chemotherapy and targeted therapy in advanced esophageal and gastroesophageal junction cancers. Cancer Res Stat Treat 2019;2:172-81. [Full text]
Kumar H, Shetty N. Primum non nocere. Cancer Res Stat Treat 2020;3:129-30. [Full text]
Joshi A, Noronha V, Pandey A, Patil V, Samar A, Mahajan A, et al
. Outcomes with palliative weekly paclitaxel in advanced, recurrent, and metastatic esophageal cancer – Real world experience. Indian J Med Paediatr Oncol 2018;39:46-51. [Full text]
Levard H, Pouliquen X, Hay JM, Fingerhut A, Langlois-Zantain O, Huguier M, et al
. 5-Fluorouracil and cisplatin as palliative treatment of advanced oesophageal squamous cell carcinoma. A multicentre randomised controlled trial. The French Associations for Surgical Research. Eur J Surg 1998;164:849-57.
Harstrick A, Bokemeyer C, Preusser P, Köhne-Wömpner CH, Meyer HJ, Stahl M, et al
. Phase II study of single-agent etoposide in patients with metastatic squamous-cell carcinoma of the esophagus. Cancer Chemother Pharmacol 1992;29:321-2.
Popa EC, Shah MA. Capecitabine in the treatment of esophageal and gastric cancers. Expert Opin Investig Drugs 2013;22:1645-57.
He S, Shen J, Hong L, Niu L, Niu D. Capecitabine “metronomic” chemotherapy for palliative treatment of elderly patients with advanced gastric cancer after fluoropyrimidine-based chemotherapy. Med Oncol 2012;29:100-6.
Kannan RA, Rangarajan B. Systemic therapy in metastatic esophageal malignancies – Time to move away from 'one size fits all (histologies)'. Cancer Res Stat Treat 2020;3:130-1. [Full text]
Shah MA, Adenis A, Enzinger PC, Kojima T, Muro K, Bennouna J, et al
. Pembrolizumab versus chemotherapy as second-line therapy for advanced esophageal cancer: Phase 3 keynote-181 study. J Clin Oncol 2019;37 Suppl 15:4010.
Philip CC, Mathew A, John MJ. Cancer care: Challenges in the developing world. Cancer Res Stat Treat 2018;1:58-62. [Full text]