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Table of Contents
MUSINGS
Year : 2018  |  Volume : 1  |  Issue : 1  |  Page : 71-74

Making a case for cancer research in India


Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra, India

Date of Web Publication12-Dec-2018

Correspondence Address:
Dr. Vanita Noronha
Department of Medical Oncology, Tata Memorial Hospital, Mumbai, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_14_18

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How to cite this article:
Noronha V. Making a case for cancer research in India. Cancer Res Stat Treat 2018;1:71-4

How to cite this URL:
Noronha V. Making a case for cancer research in India. Cancer Res Stat Treat [serial online] 2018 [cited 2019 Jun 19];1:71-4. Available from: http://www.crstonline.com/text.asp?2018/1/1/71/247326



When confronted with a complex clinical scenario, I often refer to standard oncology guidelines, published by the National Comprehensive Cancer Network and the American Society of Clinical Oncology.[1],[2] These guidelines are the distillation of evidence from multiple prior studies. Invariably, these studies have been carried out in a non-Indian patient population, yet the guidelines are widely followed in India. Certainly, there are Indian guidelines, for example, the Indian Council of Medical Research (ICMR) consensus guidelines; however, they generally echo the international guidelines rather than providing specific recommendations for Indian patients.[3]

The lacunae in oncology research in India start from a basic deficiency of good quality epidemiological data. This is gradually changing with the establishment of the Indian National Cancer Registry Program, started in 1981 by the ICMR.[4] Currently, there are 27 population-based cancer registries and some hospital-based cancer registries. As a result of the data generated by these registries, we now know that the cancer incidence in the northeastern states of India is not low as was initially perceived but is actually higher (age-adjusted incidence rate [AAIR] of 100–250 cases per 100,000 population) than the national average (AAIR of 80–100 cases per 100,000 population), giving the North East the dubious title of the 'national cancer capital of India.'[5] The limitations of the cancer registries include the fact that they do not cover the entire population and often do not include treatment and outcome data, as is done in the Surveillance, Epidemiology and End Results Program database maintained by the National Cancer Institute of America.[6]

Other gaps include a lack of adequate diagnostic and therapeutic information ranging from machinery, surgical and radiation technologies, and medicines, both chemotherapeutics and biologics. Our standard oncologic practice has been adopted without being adequately tested in the Indian research setting. Compare this to the gefitinib approval story in the USA: the Food and Drug Administration granted accelerated approval to gefitinib based on the response rate in the Phase II IDEAL trials;[7],[8] however, when the mandated Phase III ISEL trial failed to show a survival benefit,[9] they withdrew the approval for new patients, even though gefitinib continued to be approved and marketed in Europe and Asia. Sometimes, clear ethnic differences exist between oncology patients from different countries. Over 50% of our lung cancer patients are non-smokers, which is in stark contrast to reports from other countries.[10] The rate of epidermal growth factor receptor mutation in non-small cell lung cancer (NSCLC) varies from 10%-15% in North Americans and Europeans, to 25%–30% in Asians.[11],[12] The toxicity spectrum also varies. In the landmark trials that established the use of first-line pemetrexed-platinum for non-squamous NSCLC, hyponatremia was not a reported side-effect, yet 35% of our advanced NSCLC patients developed ≥Grade 3 hyponatremia when treated with this regimen.[13],[14],[15] Over 52% of our locally advanced head-and-neck squamous cell carcinoma patients treated with high-dose cisplatin chemoradiotherapy developed ≥Grade 3 hyponatremia,[16] while hyponatremia was not a reported toxicity in the landmark trials of Bernier et al. and Cooper et al.[17],[18] Hyponatremia may be a unique toxicity that occurs in our Indian patients.

Several possible explanations exist for the deficiencies in oncology research in India. There is a lack of collaboration between various stakeholders, including between institutions, between clinicians and basic scientists, between academia and the pharmaceutical industry, between investigators in different Indian states, and between Indian and international researchers. Funding is practically nonexistent, especially for interventional trials, drug trials, and instruments. Several government agencies do provide research funding like the Department of Biotechnology and the ICMR. However, most of these funds are for basic research. The results of basic and translational research are not implemented in the clinic. There is a lack of trained workforce to run clinical trials, starting from lack of research training of investigators and lack of trained research coordinators, research nurses, and data entry operators. There are very few trained biostatisticians who have an in-depth understanding of oncology trials. There is a lack of expert regulatory bodies and, for the existing regulatory bodies, there is a lack of transparency in their functioning. There is a tremendous patient load in busy academic centers. Lack of protected research time and absence of focus of the administration on research add to the demotivation.

The major academic oncology centers in India have failed to take on the mantle of research leadership. There certainly has been some seminal work done in India over the past 10 years. High-impact work has been done by Dr. Dikshit from Tata Memorial Center (TMC) and the India State Disease Burden Initiative Cancer Collaborators in epidemiology;[19],[20] Dr. Shankaranarayanan and Dr. Shastri from TMC in prevention, screening, and early detection;[21],[22],[23],[24] Dr. Dutt from TMC in genomic profiling;[25] Dr. Badwe and Dr. D'Cruz from TMC in surgical oncology;[26],[27],[28] Dr. Jalali and Dr. Srivastava from TMC in radiation oncology;[29],[30] Dr. Gupta and Dr. Prabhash from TMC; and Dr. Sharma from AIIMS in medical oncology.[16],[31],[32] This list is by no means comprehensive. But the bottom-line remains that very few landmark trials have been done in India. We certainly can and should do exponentially better.

With multiple responsibilities competing for our time and attention including patient care, administrative duties, and teaching of residents and fellows, it is easy for research to take a backseat. As clinicians, our primary training is in patient care, and that is what provides instant gratification. However, only through appropriate research activity can we understand the true scope of the cancer problem, identify and then rectify deficiencies in the system. Through oncology research in India, we could identify unique issues that our cancer patients face. We can better understand the ethnic differences between patients, the differential response to treatments, and the differential survival in various malignancies. This is the first step toward improving oncologic outcomes. Certain cancers such as oral cavity, cervical, and penile cancers are common in India; at least for these cancers, we should lead the research. Other areas uniquely suited to research in the Indian context include drug repurposing, using medications in low and frequent dosing (metronomic scheduling), and the role of alternative branches of medicine such as Ayurveda, homeopathy, and Unani. In terms of direct patient care, we believe that patients on clinical trials have the best possible outcomes, regardless of what the specific research question is, and we should strive for a future when most of our patients are enrolled in a study.

As clinicians, we make a difference in the lives of the patients we treat daily in the clinic. This impact is immediately tangible. However, this impact is limited; a very busy clinician could treat between 10 and 30 new patients a day, which works out to approximately 5000 new patients a year. To illustrate the potential impact that research could have, let us take the example of the N0 trial, done on approximately 500 Indian patients with early-stage oral cavity cancer.[28] According to GLOBOCAN 2012, there are 77,003 new oral cavity cancer patients annually in India and 300,000 worldwide.[33] Approximately 20%–40% of these patients will have early-stage disease.[34] Thus, the N0 trial results will potentially impact 23,000 early-stage oral cavity cancer patients in India and 90,000 patients globally per year.

There are some immediate actionable points that can improve the research situation in India. There should be changes in the national policy, making cancer research part of the agenda. Technology is widely available and utilized in India. Cancer registries should be established to cover an adequate population and cancer reporting should be enabled, paralleling how the Aadhaar card has been enabled for various government and nongovernment services. In all major cancer centers, there should be compulsory audits, including treatment and outcomes. Training in research methodology and establishment of a research mindset should start from undergraduate training. There should be a commitment from regulatory bodies for timely approval of trials and to encourage scientific rigor in the conduct of trials. Academic cancer centers should be rewarded for conducting and publishing practice-changing trials. Within institutions, high-quality research could be incentivized; for example, academic promotion or a commitment to fund the next trial conducted by that group of investigators. Resources should be established, in the form of workforce, funding, space, and infrastructure. Funding bodies should consider important clinical studies and should commit some funding for clinical trials. Most importantly, patients should be involved as stakeholders in the design and conduct of meaningful clinical research.

When surveyed, 66.4% of Indian patients stated that clinical research benefits society.[35] A national public opinion poll by Research! America found that 72% of Americans would be likely to participate in a clinical trial if recommended by their doctor, yet only 22% said that a doctor or health-care provider had discussed clinical trials with them and only 16% said that they or a family member had participated in a clinical trial.[36] It is estimated that worldwide, <5% of adult cancer patients are enrolled in clinical trials.[37] My hope is that the Indian oncology community and the Government of India understand sooner rather than later the importance of high-quality oncology research and that we start providing our own patients and the rest of the world with answers to the innumerable questions that currently plague the practice of oncology. When that happens, I hope to one day be able to quote George Orwell, “We shall meet in a place where there is no darkness” (1984).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Available from: https://www.nccn.org/. [Last accessed on 2018 Oct 06].  Back to cited text no. 1
    
2.
Available from: http://www.ascopubs.org/jco/site/misc/specialarticles.xhtml. [Last accessed on 2018 Oct 06].  Back to cited text no. 2
    
3.
Available from: http://www.cancerindia.org.in/icmr-consensus-documents-for-cancer-management/. [Last accessed on 2018 Sep 06].  Back to cited text no. 3
    
4.
Available from: http://www.ncdirindia.org/ncrp/. [Last accessed on 2018 Sep 30].  Back to cited text no. 4
    
5.
Available from: http://www.ncdirindia.org/Reports_Ne/NE2012_2014/Files/NE_2012_14.pdf. [Last accessed on 2018 Sep 30].  Back to cited text no. 5
    
6.
Available from: https://www.seer.cancer.gov/data/. [Last accessed on 2018 Sep 30].  Back to cited text no. 6
    
7.
Fukuoka M, Yano S, Giaccone G, Tamura T, Nakagawa K, Douillard JY, et al. Multi-institutional randomized phase II trial of gefitinib for previously treated patients with advanced non-small-cell lung cancer (The IDEAL 1 trial) [corrected]. J Clin Oncol 2003;21:2237-46.  Back to cited text no. 7
    
8.
Kris MG, Natale RB, Herbst RS, Lynch TJ Jr., Prager D, Belani CP, et al. Efficacy of gefitinib, an inhibitor of the epidermal growth factor receptor tyrosine kinase, in symptomatic patients with non-small cell lung cancer: A randomized trial. JAMA 2003;290:2149-58.  Back to cited text no. 8
    
9.
Thatcher N, Chang A, Parikh P, Rodrigues Pereira J, Ciuleanu T, von Pawel J, et al. Gefitinib plus best supportive care in previously treated patients with refractory advanced non-small-cell lung cancer: Results from a randomised, placebo-controlled, multicentre study (Iressa survival evaluation in lung cancer). Lancet 2005;366:1527-37.  Back to cited text no. 9
    
10.
Noronha V, Dikshit R, Raut N, Joshi A, Pramesh CS, George K, et al. Epidemiology of lung cancer in India: Focus on the differences between non-smokers and smokers: A single-centre experience. Indian J Cancer 2012;49:74-81.  Back to cited text no. 10
[PUBMED]  [Full text]  
11.
Noronha V, Prabhash K, Thavamani A, Chougule A, Purandare N, Joshi A, et al. EGFR mutations in Indian lung cancer patients: Clinical correlation and outcome to EGFR targeted therapy. PLoS One 2013;8:e61561.  Back to cited text no. 11
    
12.
Chougule A, Prabhash K, Noronha V, Joshi A, Thavamani A, Chandrani P, et al. Frequency of EGFR mutations in 907 lung adenocarcinoma patients of Indian ethnicity. PLoS One 2013;8:e76164.  Back to cited text no. 12
    
13.
Gota V, Kavathiya K, Doshi K, Gurjar M, Damodaran SE, Noronha V, et al. High plasma exposure to pemetrexed leads to severe hyponatremia in patients with advanced non-small cell lung cancer receiving pemetrexed-platinum doublet chemotherapy. Cancer Manag Res 2014;6:261-5.  Back to cited text no. 13
    
14.
Scagliotti GV, Parikh P, von Pawel J, Biesma B, Vansteenkiste J, Manegold C, et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer. J Clin Oncol 2008;26:3543-51.  Back to cited text no. 14
    
15.
Paz-Ares LG, de Marinis F, Dediu M, Thomas M, Pujol JL, Bidoli P, et al. PARAMOUNT: Final overall survival results of the phase III study of maintenance pemetrexed versus placebo immediately after induction treatment with pemetrexed plus cisplatin for advanced nonsquamous non-small-cell lung cancer. J Clin Oncol 2013;31:2895-902.  Back to cited text no. 15
    
16.
Noronha V, Joshi A, Patil VM, Agarwal J, Ghosh-Laskar S, Budrukkar A, et al. Once-a-week versus once-every-3-weeks cisplatin chemoradiation for locally advanced head and neck cancer: A phase III randomized noninferiority trial. J Clin Oncol 2018;36:1064-72.  Back to cited text no. 16
    
17.
Bernier J, Domenge C, Ozsahin M, Matuszewska K, Lefèbvre JL, Greiner RH, et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 2004;350:1945-52.  Back to cited text no. 17
    
18.
Cooper JS, Pajak TF, Forastiere AA, Jacobs J, Campbell BH, Saxman SB, et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 2004;350:1937-44.  Back to cited text no. 18
    
19.
Dikshit R, Gupta PC, Ramasundarahettige C, Gajalakshmi V, Aleksandrowicz L, Badwe R, et al. Cancer mortality in India: A nationally representative survey. Lancet 2012;379:1807-16.  Back to cited text no. 19
    
20.
India State-Level Disease Burden Initiative Cancer Collaborators. The burden of cancers and their variations across the states of India: The Global Burden of Disease Study 1990-2016. Lancet Oncol 2018;19:1289-1306.  Back to cited text no. 20
    
21.
Sankaranarayanan R, Nene BM, Shastri SS, Jayant K, Muwonge R, Budukh AM, et al. HPV screening for cervical cancer in rural India. N Engl J Med 2009;360:1385-94.  Back to cited text no. 21
    
22.
Sankaranarayanan R, Prabhu PR, Pawlita M, Gheit T, Bhatla N, Muwonge R, et al. Immunogenicity and HPV infection after one, two, and three doses of quadrivalent HPV vaccine in girls in India: A multicentre prospective cohort study. Lancet Oncol 2016;17:67-77.  Back to cited text no. 22
    
23.
Sankaranarayanan R, Ramadas K, Thara S, Muwonge R, Prabhakar J, Augustine P, et al. Clinical breast examination: Preliminary results from a cluster randomized controlled trial in India. J Natl Cancer Inst 2011;103:1476-80.  Back to cited text no. 23
    
24.
Shastri SS, Mittra I, Mishra GA, Gupta S, Dikshit R, Singh S, et al. Effect of VIA screening by primary health workers: Randomized controlled study in Mumbai, India. J Natl Cancer Inst 2014;106:dju009.  Back to cited text no. 24
    
25.
Chandrani P, Prabhash K, Prasad R, Sethunath V, Ranjan M, Iyer P, et al. Drug-sensitive FGFR3 mutations in lung adenocarcinoma. Ann Oncol 2017;28:597-603.  Back to cited text no. 25
    
26.
Badwe R, Hawaldar R, Nair N, Kaushik R, Parmar V, Siddique S, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: An open-label randomised controlled trial. Lancet Oncol 2015;16:1380-8.  Back to cited text no. 26
    
27.
Badwe R, Hawaldar R, Parmar V, Nadkarni M, Shet T, Desai S, et al. Single-injection depot progesterone before surgery and survival in women with operable breast cancer: A randomized controlled trial. J Clin Oncol 2011;29:2845-51.  Back to cited text no. 27
    
28.
D'Cruz AK, Vaish R, Kapre N, Dandekar M, Gupta S, Hawaldar R, et al. Elective versus therapeutic neck dissection in node-negative oral cancer. N Engl J Med 2015;373:521-9.  Back to cited text no. 28
    
29.
Jalali R, Gupta T, Goda JS, Goswami S, Shah N, Dutta D, et al. Efficacy of stereotactic conformal radiotherapy vs. conventional radiotherapy on benign and low-grade brain tumors: A Randomized clinical trial. JAMA Oncol 2017;3:1368-76.  Back to cited text no. 29
    
30.
Shrivastava S, Mahantshetty U, Engineer R, Chopra S, Hawaldar R, Hande V, et al. Cisplatin chemoradiotherapy vs radiotherapy in FIGO stage IIIB squamous cell carcinoma of the uterine cervix: A Randomized clinical trial. JAMA Oncol 2018;4:506-13.  Back to cited text no. 30
    
31.
Gupta S, Maheshwari A, Parab P, Mahantshetty U, Hawaldar R, Sastri Chopra S, et al. Neoadjuvant chemotherapy followed by radical surgery versus concomitant chemotherapy and radiotherapy in patients with stage IB2, IIA, or IIB squamous cervical cancer: A randomized controlled trial. J Clin Oncol 2018;36:1548-55.  Back to cited text no. 31
    
32.
Sharma A, Dwary AD, Mohanti BK, Deo SV, Pal S, Sreenivas V, et al. Best supportive care compared with chemotherapy for unresectable gall bladder cancer: A randomized controlled study. J Clin Oncol 2010;28:4581-6.  Back to cited text no. 32
    
33.
Ferlay J, Soerjomataram I, Ervik M, Dikshit R, Eser S, Mathers C, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 11. Lyon, France: International Agency for Research on Cancer; 2013.  Back to cited text no. 33
    
34.
Coelho KR. Challenges of the oral cancer burden in India. J Cancer Epidemiol 2012;2012:701932.  Back to cited text no. 34
    
35.
Kapadia K. Understanding patients perspective on clinical research in Indian population. J Clin Res Bioeth 2015;6:229.  Back to cited text no. 35
    
36.
37.
Unger JM, Cook E, Tai E, Bleyer A. The role of clinical trial participation in cancer research: Barriers, evidence, and strategies. Am Soc Clin Oncol Educ Book 2016;35:185-98.  Back to cited text no. 37
    




 

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