Assume there is a patient with oral tongue SCC (pT3N1) underwent surgery (R0) and postop con. ChemoRT with weekly cisplatin. One month after completion a reccurence emerges in the radiated field. You want to start palliative chemo. Do you consider this patient as resistant to Cisplatin and choose other non-cis drugs? or Add something to Cis?
According to the published literature, I choose the latter approach. Currently, Cisplatin (100 mg/m2 intravenous, day 1) and fluorouracil (1000 mg/m2 per day, continuous infusion, for four days) is a standard combination chemotherapy regimen for use in the palliative setting (1).
1. Brockstein B, Vokes E. Treatment of metastatic and recurrent head and neck cancer. UpToDate. UpToDate, Waltham. 2013.
@farzad taghizadeh
Thanks a lot Farzad, in my opinion there is a lack of data in such setting. Why we should test a combination including a drug that we know is non-effective?!!
Reza Ghalehtaki
Dear Reza, I appreciate for your kind attention and especially for bringing this dilemma up.
According to the published literature, the response rate for cisplatin-naïve head and neck carcinoma is approximately 50%. However, this rate is much lower in recurrent cases. There are a number of mechanisms that induce Cisplatin resistance in head and neck carcinoma (e.g. membrane transporters for cisplatin uptake or efflux, such as CRT1 and ABC transporter MRP2; DNA repair proteins, such as ERCC1 and TP53; apoptosis associated proteins including BCL-2, caspases, or MAPKs) (1). Moreover, Chang et al. showed alternate enzymatic pathway for Cisplatin resistance in head and neck carcinoma. They depict AKR1C1 induce Cisplatin resistance through activation of STAT1/3 (2).
Therefore, as is evident, due to enzymatic processes involved in Cisplatin- resistance, Cisplatin in second-line is expected to have clinical activity.
1. Galluzzi L, Senovilla L, Vitale I, Michels J, Martins I, Kepp O, Castedo M, Kroemer G. Molecular mechanisms of cisplatin resistance. Oncogene. 2012;31:1869–83.
2. Chang WM, Chang YC, Yang YC, Lin SK, Chang PM, Hsiao M. AKR1C1 controls cisplatin-resistance in head and neck squamous cell carcinoma through cross-talk with the STAT1/3 signaling pathway. Journal of Experimental & Clinical Cancer Research. 2019 Dec;38(1):245.
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