HAEMATOLOGICAL TOXICITIES OF GEMCITABINE PLUS CISPLATIN VERSUS FLUOROURACIL, CISPLATIN, PLUS DOCETAXEL FOLLOWED BY CONCURRENT CHEMORADIOTHERAPY IN LOCOREGIONALLY ADVANCED NASOPHARYNGEAL CARCINOMA

Authors

  • Abdul Rehman Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan
  • Ghulam Haider Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan
  • Aakash Ramchand Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan
  • Shumaila Nawaz Khan Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan
  • Sana Saher Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan
  • Raheela Mahmood Atomic Energy Medical Centre, JPMC Karachi Pakistan
  • Yasir Rehman Khattak Hayatabad Medical Complex, Peshawar-Pakistan
  • Anaum Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan
  • Aisha Siddiqua Atomic Energy Medical Centre, JPMC Karachi Pakistan
  • Muhammad Arsalan Aqeel Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan

Keywords:

imaging, haematological toxicity, neoadjuvant chemotherapy, diagnosis

Abstract

Background: Nasopharyngeal carcinoma is endowed with unique epidemiological characteristics, treatment modalities, and prognostic considerations. Patients with bulky primary tumours and extensive nodal involvement are categorized as locoregionally advanced NPC. These patients present a high-risk cohort in terms of the unfavourable prognostic features. In this patient cohort, the 5-year local control rates have been observed to fluctuate within the range of 69–79%. The objective was the assessment of the local control and adverse haematological toxicity profiles of neoadjuvant chemotherapy (NACT) (i.e., docetaxel, cisplatin, plus fluorouracil (TCF) and gemcitabine plus cisplatin (GC)) followed by concurrent chemoradiotherapy (CCRT) in patients with locoregionally advanced nasopharyngeal carcinoma (LANPC) was the primary objective of this work. Methods: Patients aged 16–65 years, confirmed NPC, stage III-IVA disease and ECOG performance score ≤2 were enrolled in this prospective study. Besides the common CCRT regimen, the patients received NACT with docetaxel 30 mg/m2, cisplatin 40 mg/m2 plus fluorouracil 750 mg/m2 (Group I) or gemcitabine 1 g/m2 plus cisplatin 80 mg/m2 (Group II). At 6 weeks after completion of CCRT, treatment response was assessed with the RECIST criteria. Adverse haematological events were evaluated with peripheral white blood cells, neutrophils, haemoglobin, and platelets after each cycle of NACT. Results: Of the total 68 enrolled patients with locoregionally advanced NPC (LANPC), 50 (73.5%) were male patients. Group I consisted of 36, while Group II comprised 32 patients. The mean (interquartile range) age of the patients in Group I was 40.9±11.6 (30.3–51.8) years, while in Group II was 38.6±11.3 (29.5–51.0) years. Complete response (CR) of the treatment was higher and partial response (PR) was lower in Group II compared to Group I (71.9% vs. 44.4% and 18.6% vs. 50%, respectively). Haematological toxicity profiles were consistent in Groups I and II, illustrating mild anaemia and lymphopenia, severe neutropenia and a mixed pattern of thrombocytopenia. Conclusion: Among patients with LANPC, GC-based NACT showed superior CR compared with TCF-based NACT. However, the haematological toxicity profiles in the two groups were comparable.

Author Biographies

Abdul Rehman, Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan

 

Ghulam Haider, Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan

 

Aakash Ramchand , Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan

 

Shumaila Nawaz Khan, Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan

 

Sana Saher , Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan

 

Raheela Mahmood , Atomic Energy Medical Centre, JPMC Karachi Pakistan

 

Yasir Rehman Khattak, Hayatabad Medical Complex, Peshawar-Pakistan

 

Anaum , Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan

 

Aisha Siddiqua , Atomic Energy Medical Centre, JPMC Karachi Pakistan

 

Muhammad Arsalan Aqeel, Jinnah Postgraduate Medical Centre (JPMC) Karachi-Pakistan

 

References

Liu Y, Du Z, Song S, Yi J. Progress in the comprehensive treatment of nasopharyngeal carcinoma: a review for risk ‑ stratified management strategies. Holist Integr Oncol. 2023;2(1):19.

Meng Y, Huang C, Huang W. Survival after induction chemotherapy in locoregional advanced nasopharyngeal carcinoma: An updated systematic review and meta-analysis. Laryngoscope Investig Otolaryngol 2023;8(5):1217–25.

Xu K, De Ravin E, Suresh N, Brody RM, Rajasekaran K. A comprehensive review and characterization of nasopharyngeal carcinoma clinical trials. World J Otorhinolaryngol Head Neck Surg 2023;9(2):174–82.

Xu AA, Miao JJ, Wang L, Li AC, Han F, Shao XF, et al. Efficacy of concurrent chemoradiotherapy alone for loco-regionally advanced nasopharyngeal carcinoma: long-term follow-up analysis. Radiat Oncol. 2023;18(1):63.

Zhu F, Wu Y, Wang H. Advance in integrating platinum-based chemotherapy with radiotherapy for locally advanced nasopharyngeal carcinoma. Front Oncol 2023;13:1259331.

Niu X, Liu P, Zhou X, Ou D, Wang X, Hu C. Anti-epidermal growth factor receptor (EGFR) monoclonal antibody combined with chemoradiotherapy for induction chemotherapy resistant locally advanced nasopharyngeal carcinoma: A prospective phase II study. Transl Oncol 2024;39:101797.

Tang LQ, Chen DP, Guo L, Mo HY, Huang Y, Guo SS, et al. Concurrent chemoradiotherapy with nedaplatin versus cisplatin in stage II–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised phase 3 trial. Lancet Oncol 2018;19(4):461–73.

Chen YP, Tang LL, Yang Q, Poh SS, Hui EP, Chan ATC, et al. Induction chemotherapy plus concurrent chemoradiotherapy in endemic nasopharyngeal carcinoma: Individual patient data pooled analysis of four randomized trials. Clin Cancer Res 2018;24(8):1824–33.

Zhang LL, Zheng W hong, Zhu W jie, Deng QL, Peng JL, Li YY, et al. Prognostic models for early and late tumor progression prediction in nasopharyngeal carcinoma: An analysis of 8292 endemic cases. Cancer Med 2023;12(5):5384–96.

Luo Y, Xiang XJ, Ma XJ. Clinical observational study on the efficacy of induction chemotherapy sequential concurrent radiotherapy combined with targeted therapy in patients with locally advanced EGFR-positive nasopharyngeal carcinoma: prediction model construction and efficacy testing. Eur Arch Otorhinolaryngol 2023;280(12):5409–16.

Luo Y, Cai B, Li B, Liu F, Du L, Zhao D, et al. The Acute Toxicities and Efficacy of Concurrent Chemotherapy With Docetaxel Plus Cisplatin, or Docetaxel, or Cisplatin and Helical Tomotherapy in Patients With Locoregionally Advanced Nasopharyngeal Carcinoma: A Randomized Single-Center Phase II Trial. Technol Cancer Res Treat 2022;21(28):15330338221109974.

Pala M, Novakova P, Drbohlavova T, Vrana A, Pechacova Z, Votavova K, et al. Negative Prognostic Impact of Smoking on Long-term Survival in Patients with Nasopharyngeal Carcinoma Treated With Curative (Chemo)radiotherapy. In Vivo (Brooklyn) 2023;37(4):1775–85.

Posner MR, Hershock DM, Blajman CR, Mickiewicz E, Winquist E, Gorbounova V, et al. Cisplatin and Fluorouracil Alone or with Docetaxel in Head and Neck Cancer. N Engl J Med 2007;357(17):1705–15.

Albers AE, Grabow R, Qian X, Jumah MD, Hofmann VM, Krannich A, et al. Efficacy and toxicity of docetaxel combination chemotherapy for advanced squamous cell cancer of the head and neck. Mol Clin Oncol 2017;7(1):151–7.

Hu W, Fang L, Ni R, Zhang H, Pan G. Changing trends in the disease burden of non-melanoma skin cancer globally from 1990 to 2019 and its predicted level in 25 years. BMC Cancer 2022;22:836.

Baba M, Singh B, Wani SU. Skin sparing in intensity-modulated radiation therapy of nasopharyngeal carcinoma. J Med Phys 2022;47(3):243–9.

Wu LR, Liu YT, Jiang N, Fan YX, Wen J, Huang SF, et al. Ten-year survival outcomes for patients with nasopharyngeal carcinoma receiving intensity-modulated radiotherapy: An analysis of 614 patients from a single center. Oral Oncol 2017;69:26–32.

Deng C, Zhang N, Jiang S, Zhang H, Ma J, Zou W, et al. Nedaplatin-based chemotherapy or cisplatin-based chemotherapy combined with intensity-modulated radiotherapy achieve similar efficacy for stage II-IVa nasopharyngeal carcinoma patients. Sci Rep 2022;12:11978.

Huang YY, Zhou JY, Zhan ZJ, Ke LR, Xia WX, Cao X, et al. Tumor residue in patients with stage II–IVA nasopharyngeal carcinoma who received intensity-modulated radiation therapy: development and validation of a prediction nomogram integrating postradiotherapy plasma Epstein–Barr virus deoxyribonucleic acid, clin. BMC Cancer 2023;23(1):410.

Tsai MH, Wu SY, Lu HH, Yu T, Tsai ST, Wu YH. Improved overall survival is associated with adjuvant chemotherapy after definitive concurrent chemoradiotherapy for N3 nasopharyngeal cancer. Sci Rep 2022;12:13390.

Juarez-Vignon Whaley JJ, Afkhami M, Sampath S, Amini A, Bell D, Villaflor VM. Early Stage and Locally Advanced Nasopharyngeal Carcinoma Treatment from Present to Future: Where Are We and Where Are We Going? Curr Treat Options Oncol 2023;24(7):845–66.

He Y, Guo T, Guan H, Wang J, Sun Y, Peng X. Concurrent chemoradiotherapy versus radiotherapy alone for locoregionally advanced nasopharyngeal carcinoma in the era of intensitymodulated radiotherapy: A meta-analysis. Cancer Manag Res 2018;10:1419–28.

Zou R, Yuan JJ, Li Q, Ding JW, Liao B, Tu ZW, et al. The Clinical Outcomes and Toxicities of Induction Chemotherapy Followed by Concurrent Chemoradiotherapy Plus Adjuvant Chemotherapy in Locoregionally Advanced Nasopharyngeal Carcinoma. Front Oncol 2021;10:2020.

Tang LL, Chen L, Hu CS, Yi JL, Li JG, He X, et al. CACA guidelines for holistic integrative management of nasopharyngeal carcinoma. Holist Integr Oncol 2023;2:1.

Chan ATC, Hui EP, Ngan RKC, Tung SY, Cheng ACK, Ng WT, et al. Analysis of plasma Epstein-Barr virus DNA in nasopharyngeal cancer after chemoradiation to identify high-risk patients for adjuvant chemotherapy: A randomized controlled trial. J Clin Oncol 2018;36(31):3091–100.

Wu Q, Zhu C, Zhang S, Zhou Y, Zhong Y. Hematological Toxicities of Concurrent Chemoradiotherapies in Head and Neck Cancers: Comparison Among Cisplatin, Nedaplatin, Lobaplatin, and Nimotuzumab. Front Oncol 2021;11:762366.

Hung CJ, Kang BH, Chang KM, Kang YY, Yin CH, Lee CC. Chemotherapy dose per kilogram lean body mass increased dose-limiting toxicity event in male head and neck cancer with taxane and platinum-based induction therapy. BMC Cancer 2022;22(1):1084.

Zhou R, Zhu J, Chen X, Liu Y, Wang Y, Zhang T. The efficacy and safety of docetaxel, cisplatin and fluorouracil (TPF)-based induction chemotherapy followed by concurrent chemoradiotherapy for locoregionally advanced nasopharyngeal carcinoma: a meta-analysis. Clin Transl Oncol 2020;22(3):429–39.

Bongiovanni A, Vagheggini A, Fausti V, Mercatali L, Calpona S, Di Menna G, et al. Induction chemotherapy plus concomitant chemoradiotherapy in nasopharyngeal carcinoma: An updated network meta-analysis. Crit Rev Oncol Hematol 2021;160:103244.

Zeng Z, Yan RN, Tu L, Wang YY, Chen PR, Luo F, et al. Assessment of Concurrent Chemoradiotherapy plus Induction Chemotherapy in Advanced Nasopharyngeal Carcinoma: Cisplatin, Fluorouracil, and Docetaxel versus Gemcitabine and Cisplatin. Sci Rep 2018;8:15581.

Hennessy MA, Morris PG. Induction treatment prior to chemoradiotherapy in nasopharyngeal carcinoma: triplet or doublet chemotherapy? Anticancer Drugs 2020;31(2):97–100.

Manitz J, D’Angelo SP, Apolo AB, Eggleton SP, Bajars M, Bohnsack O, et al. Comparison of tumor assessments using RECIST 1.1 and irRECIST, and association with overall survival. J Immunother Cancer 2022;10(2):e003302.

Sun Y, Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, et al. Induction chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone in locoregionally advanced nasopharyngeal carcinoma: a phase 3, multicentre, randomised controlled trial. Lancet Oncol 2016;17(11):1509–20.

Mi JL, Zhang B, Pan YF, Su YX, Fan JF, Liao SF, et al. Chemotherapy regimens containing taxanes or fluorouracil in nasopharyngeal carcinoma: Which better? Oral Oncol 2017;74:34–9.

Lv X, Cao X, Xia WX, Liu KY, Qiang MY, Guo L, et al. Induction chemotherapy with lobaplatin and fluorouracil versus cisplatin and fluorouracil followed by chemoradiotherapy in patients with stage III–IVB nasopharyngeal carcinoma: an open-label, non-inferiority, randomised, controlled, phase 3 trial. Lancet Oncol 2021;22(5):716–26.

Fang W, Yang Y, Ma Y, Hong S, Lin L, He X, et al. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol 2018;19(10):1338–50.

Mai HQ, Chen QY, Chen D, Hu C, Yang K, Wen J, et al. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med 2021;27(9):1536–43.

Oeffinger KC, Hudson MM. Long-term Complications Following Childhood and Adolescent Cancer: Foundations for Providing Risk-based Health Care for Survivors. CA Cancer J Clin 2004;54(4):208–36.

Zhang Y, Chen M, Chen C, Kong L, Lu JJ, Xu B. The efficacy and toxicities of intensive induction chemotherapy followed by concurrent chemoradiotherapy in nasopharyngeal carcinoma patients with N3 disease. Sci Rep 2017;7:3668.

Zhang Y, Chen L, Hu GQ, Zhang N, Zhu XD, Yang KY, et al. Gemcitabine and Cisplatin Induction Chemotherapy in Nasopharyngeal Carcinoma. N Engl J Med 2019;381(12):1124–35.

Li WF, Chen NY, Zhang N, Hu GQ, Xie FY, Sun Y, et al. Concurrent chemoradiotherapy with/without induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma: Long-term results of phase 3 randomized controlled trial. Int J Cancer 2019;145(1):295–305.

Aldossary SA. Review on pharmacology of cisplatin: Clinical use, toxicity and mechanism of resistance of cisplatin. Biomed Pharmacol J 2019;12(1):7–15.

Published

2024-03-30

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