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Table of Contents
Year : 2018  |  Volume : 1  |  Issue : 2  |  Page : 181-182

Introspection to abandon the 'Comfort Zone': Weekly cisplatin no more

Department of Medical Oncology, IGIMS, Patna, Bihar, India

Date of Web Publication17-May-2019

Correspondence Address:
Avinash Pandey
Department of Medical Oncology, IGIMS, Patna, Bihar
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/CRST.CRST_1_19

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How to cite this article:
Pandey A, Singh A. Introspection to abandon the 'Comfort Zone': Weekly cisplatin no more. Cancer Res Stat Treat 2018;1:181-2

How to cite this URL:
Pandey A, Singh A. Introspection to abandon the 'Comfort Zone': Weekly cisplatin no more. Cancer Res Stat Treat [serial online] 2018 [cited 2020 Jan 20];1:181-2. Available from: http://www.crstonline.com/text.asp?2018/1/2/181/258529

With great interest, we read the recently published “Once-a-week versus once-every-3-weeks cisplatin in patients receiving chemoradiation for locally advanced head-and-neck cancer: A survey of practice in India” by Goyal et al. in your last issue of Cancer Research, Statistics and Treatment journal.[1] Weekly cisplatin schedule (87.9%) triumphs over three-weekly cisplatin 100 mg/m2 (8.9%) as the most favored choice in community practice. Majority of the respondents were radiation oncologists (63.8%), in private oncology setup (47.9%), and relatively young in practice (44%). Better tolerance (59.5%) of weekly cisplatin was the most common reason cited for preference. More interesting was to acknowledge that, when it comes to making a choice of the dose of weekly cisplatin, only 25% of the responders mentioned 30 mg/m2 weekly, whereas 60% preferred 40 mg/m2 weekly schedule. This skewed response toward weekly cisplatin compared to three-weekly cisplatin is largely due to equivocal and insufficiently explored question of equivalence/superiority of one schedule over another (gray-zone evidence) compounded by a bias of young physicians trained in centers using predominantly weekly schedule, despite good evidence to support one over the other.

In India, the choice of weekly cisplatin as the chemotherapy schedule is driven largely by major academic centers' preference for this regime with concern for higher toxicity in three-weekly regimes. Gupta et al. in a retrospective review of 264 patients justified weekly cisplatin 30 mg/m2 as the preferred candidate for optimum regime for concurrent chemoradiotherapy with 5-year local control of 57% and acceptable Grade 3 mucositis (29%), with two-thirds of the patients receiving planned dose of cisplatin.[2] Moreover, in subsequent prospective trials, researchers from the same institute continued weekly cisplatin 30 mg/m2 as the control arm in concurrent chemotherapy for comparing outcomes with accelerated hyperfractioned radiotherapy and conventional radiotherapy.[3],[4] Ghosh-Laskar et al. showed better locoregional control (49% vs. 32% at 5 years, P = 0.049) favoring concurrent chemoradiotherapy.[3] Another premier Indian institute used 40 mg/m2 of weekly cisplatin in a Phase II randomized trial comparing chemoradiotherapy versus radiotherapy alone in predominantly oropharyngeal carcinoma in the definitive setting. They demonstrated better locoregional control and overall survival albeit 40% of patients receiving weekly cisplatin required admission for Grade 3 mucositis.[5]

Two large seminal trials EORTC22931 and RTOG 9501 established the role of three-weekly cisplatin over radiotherapy alone in postoperative and definitive setting with significant benefit in locoregional control and overall survival.[6],[7] However, citing reasons of ease of administration, less supportive care requirements, lower toxicity, and increased dose intensity, weekly cisplatin sneaked ahead across the globe, especially in low-resource countries. Not only did it become the standard control arm in prospective randomized trials (ClinicalTrials.gov identifiers: NCT01810913 and NCT02923258), but also found its place in clinical guidelines as the preferred choice in Asian countries citing “preferred clinical practice” as sole raison d'être.[8] Cautiously, the National Comprehensive Cancer Network guidelines granted category 2B status for weekly cisplatin 40 mg/m2, while retaining 100 mg/m2 three-weekly as standard Level I evidence as the preferred concurrent chemotherapy schedule.[9] In contrast to the above, a recent Indian Phase III trial comparing weekly cisplatin (30 mg/m2) with conventional radiotherapy failed to demonstrate any benefit of concurrent chemoradiotherapy over radiotherapy alone, thus highlighting that the uniform use of weekly cisplatin schedule across all populations may be suboptimal and exploration of three-weekly cisplatin should be prodded more.[4]

Recently, Noronha et al. reported one of the largest randomized noninferiority Phase III trials of concurrent weekly cisplatin 30 mg/m2 versus once every 3-week cisplatin 100 mg/m2 (high dose) for definitive and adjuvant chemoradiotherapy for Stage III and IV head-and-neck squamous cell carcinoma.[10] The majority of the 300 randomly assigned patients had oral cavity squamous cell carcinoma and received treatment in the adjuvant setting (92.7% in the weekly arm vs. 93.3% in the high-dose arm). Completion of planned treatment was achieved in 94% in the high-dose arm and in 88.7% in the weekly arm. The trial demonstrated a significant difference in the 2-year locoregional control rate, the primary endpoint: 58.5% in the weekly arm and 73.1% in the high-dose arm (P = 0.014; hazard ratio, 1.76 [95% confidence interval, 1.11–2.79]) after a median follow-up of 22 months. The progression-free survival (PFS) results favored the high-dose arm, but there were no significant differences in PFS or overall survival. This should reasonably settle the debate in favor of using 100 mg/m2 every 3 weeks concurrently with radiotherapy as a new standard choice for at least all oral cavity postoperative chemoradiation. Those who are still skeptical and wondering whether 40 mg/m2 could withstand the formidable challenge for three-weekly concurrent cisplatin will have to eagerly await the outcomes of two randomized clinical trials addressing the above question.

Hence, in view of the above, it is pertinent for the Indian oncology community to acquaint themselves with the above limitation of low-dose weekly concurrent cisplatin (30 mg/m2) and consider switching to three-weekly cisplatin in young, fit cisplatin-eligible candidates planned for curative postoperative chemoradiation of oral cavity cancer.

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There are no conflicts of interest.

  References Top

Goyal G, Patil VM, Noronha V, Joshi A, Khaddar S, Kakkar S, et al. Once-a-week versus once-every-3-weeks cisplatin in patients receiving chemoradiation for locally advanced head-and-neck cancer: A survey of practice in India. Cancer Res Stat Treat 2018;1:63.  Back to cited text no. 1
  [Full text]  
Gupta T, Agarwal JP, Ghosh-Laskar S, Parikh PM, D'Cruz AK, Dinshaw KA, et al. Radical radiotherapy with concurrent weekly cisplatin in loco-regionally advanced squamous cell carcinoma of the head and neck: A single-institution experience. Head Neck Oncol 2009;1:17.  Back to cited text no. 2
Ghosh-Laskar S, Kalyani N, Gupta T, Budrukkar A, Murthy V, Sengar M, et al. Conventional radiotherapy versus concurrent chemoradiotherapy versus accelerated radiotherapy in locoregionally advanced carcinoma of head and neck: Results of a prospective randomized trial. Head Neck 2016;38:202-7.  Back to cited text no. 3
Laskar SG, Chaukar D, Deshpande M, Chatterjee A, Hawaldar RW, Chakraborty S, et al. Phase III randomized trial of surgery followed by conventional radiotherapy (5 fr/Wk) (Arm A) vs. concurrent chemoradiotherapy (Arm B) vs. accelerated radiotherapy (6fr/Wk) (Arm C) in locally advanced, stage III and IV, resectable, squamous cell carcinoma of oral cavity-oral cavity adjuvant therapy (OCAT): Final results (NCT00193843) 2016;6004.  Back to cited text no. 4
Sharma A, Mohanti BK, Thakar A, Bahadur S, Bhasker S. Concomitant chemoradiation versus radical radiotherapy in advanced squamous cell carcinoma of oropharynx and nasopharynx using weekly cisplatin: A phase II randomized trial. Ann Oncol 2010;21:2272-7.  Back to cited text no. 5
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. 6
Cooper JS, Zhang Q, Pajak TF, Forastiere AA, Jacobs J, Saxman SB, et al. Long-term follow-up of the RTOG 9501/intergroup phase III trial: Postoperative concurrent radiation therapy and chemotherapy in high-risk squamous cell carcinoma of the head and neck. Int J Radiat Oncol Biol Phys 2012;84:1198-205.  Back to cited text no. 7
D'cruz A, Lin T, Anand AK, Atmakusuma D, Calaguas MJ, Chitapanarux I, et al. Consensus recommendations for management of head and neck cancer in Asian countries: A review of international guidelines. Oral Oncol 2013;49:872-7.  Back to cited text no. 8
National Comprehensive Cancer Network: NCCN Clinical Practice Guidelines in Oncology, NCCN Evidence Blocks: Head and Neck Cancers Version 2; 2017. Available from: https://www.nccn.org/professionals/physician_gls/pdf/head-and-neck.pdf. [Last assessed on 2018 Dec 25].  Back to cited text no. 9
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. 10


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