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Abstract
BACKGROUND
Concurrent chemoradiation (CCRT) is the standard of care for locally advanced head and neck squamous cell carcinoma (LAHNSCC). In settings with considerable waiting period for radiation, institutional protocols advocate induction chemotherapy before CCRT. This study aimed to assess the outcome of concurrent chemoradiation after induction of chemotherapy among patients with LAHNSCC attending a tertiary care radiotherapy center in Kerala, India.
METHODS
Patients with non-metastatic LAHNSCC (stage 111 and 1V) with good performance score of 0-1 who received induction chemotherapy (with docetaxel 75mg/m2and cisplatin 75 mg/m2, day 1 and 5-fluorouracil 750 mg/m2, day 1 and 2 as infusion every 3 weeks for 3 cycles) followed by CCRT (with concurrent cisplatin 40 mg/m2 weekly) were selected for the study. CCRT was administered only to those patients who showed more than 30 % response to induction chemotherapy. They were followed up for 24 months. The primary end point was the clinical response assessed by ENT evaluation 8 weeks after the completion of CCRT.
RESULTS
117 patients with LAHNSCC were enrolled. Four patients (3.4 %) dropped out after induction therapy. Out of 113 patients who initiated concurrent chemo radiation, two patients (1.7 %) dropped out while on CCRT, two patients (1.7 %) were intolerant to CCRT and two patients (1.7 %) left soon after CCRT. 107 patients were available for follow up after treatment completion. Acute toxicities were noticed in 9 (7.7 %) while on induction treatment. Mucositis occurred in 1 (0.9 %), haematological toxicities in 4 (3.4 %), gastrointestinal toxicities in 2 (1.7 %) and fatigue and malaise in 2 (1.7 %). In patients who underwent concurrent chemo radiation, 53 (49.03 %) had acute mucosal, skin, GIT and haematological toxicities. On treatment completion, 82 patients (70.1 %) had complete response, 24 (20.5 %) had partial response and one (0.9 %) had stable disease. During the follow up period of 24 months, locoregional failure (relapse) was noted in 15 patients (12.8 %) while 61 patients (52.1 %) remained disease free. Organ preservation rate was 53.4 % for laryngeal primaries. 4 patients (3.4 %) developed distant metastases during the follow up.
CONCLUSIONS
Induction chemotherapy with docetaxel containing regime followed by concurrent chemoradiation was associated with good clinical response and acceptable toxicity profile.
Keywords
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References
- Prabhash K, Babu G, Chaturvedi P, et al. Indian clinical practice consensus guidelines for the management of squamous cell carcinoma of head and neck. Indian J Cancer 2020;57(Suppl):S1-5.
- Ensley JF, Jacobs JR, Weaver A, et al. Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck. Cancer 1984;54(5):811-4.
- Wolf GT, Fisher SG, Hong WK, et al. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991;324(24):1685-90.
- Lefebvre JL, Chevalier D, Luboinski B, et al. Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 1996;88(13):890-9.
- Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 2013;31(7):845-52.
- Pointreau Y, Garaud P, Chapet S, et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst 2009;101(7):498-506.
- Posner MR, Norris CM, Wirth LJ, et al. Sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in TAX 324: survival, surgery, and organ preservation. Ann Oncol 2009;20(5):921-7.
- NCCN Guidelines 2020 of head and neck cancer.
- Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003;21(1):92-8.
- Pignon JP, le Maître A, Maillard E, Bet al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92(1):4-14.
- Seiwert TY. Salama JK Vokes EE. The concurrent chemoradiation paradigm--general principles. Nat Clin Pract Oncol 2007;4(2):86-100.
- Gupta T, Agarwal JP, Ghosh-Laskar S, 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.
- Vermorken JB, Remenar E, Van Herpen C, et al. Standard cisplatin/infusional 5-fluorouracil (PF) vs docetaxel (T) plus PF (TPF) as neoadjuvant chemotherapy for nonresectable locally advanced squamous cell carcinoma of the head andneck (LA-SCCHN): a phase III trial of the EORTC Head and Neck Cancer Group (EORTC# 24971). J Clin Oncol 2004;22(14_Suppl):5508.
- Kim R, Hahn S, Shin J, et al. The effect of induction chemotherapy using docetaxel, cisplatin, and fluorouracil on survival in locally advanced head and neck squamous cell carcinoma: a meta-analysis. Cancer Res Treat 2016;48(3):907-16.
- Bonomo P, Livi L. De-intensification for HPV positive oropharyngeal cancer: and yet it moves!: 2019 in review. Clin Transl Radiat Oncol 2020;22:40-43.
- Meulemans J, Debacker J, Demarsin H, et al. Oncologic outcomes after salvage laryngectomy for squamous cell carcinoma of the larynx and hypopharynx: a multicenter retrospective cohort study. Ann Surg Oncol 2021;28(3):1751-61.
- Cohen EE, Haraf DJ, Kunnavakkam R, et al. Epidermal growth factor receptor inhibitor gefitinib added to chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol 2010;28(20):3336-43.
References
Prabhash K, Babu G, Chaturvedi P, et al. Indian clinical practice consensus guidelines for the management of squamous cell carcinoma of head and neck. Indian J Cancer 2020;57(Suppl):S1-5.
Ensley JF, Jacobs JR, Weaver A, et al. Correlation between response to cisplatinum-combination chemotherapy and subsequent radiotherapy in previously untreated patients with advanced squamous cell cancers of the head and neck. Cancer 1984;54(5):811-4.
Wolf GT, Fisher SG, Hong WK, et al. Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer. N Engl J Med 1991;324(24):1685-90.
Lefebvre JL, Chevalier D, Luboinski B, et al. Larynx preservation in pyriform sinus cancer: preliminary results of a European Organization for Research and Treatment of Cancer phase III trial. EORTC Head and Neck Cancer Cooperative Group. J Natl Cancer Inst 1996;88(13):890-9.
Forastiere AA, Zhang Q, Weber RS, et al. Long-term results of RTOG 91-11: a comparison of three nonsurgical treatment strategies to preserve the larynx in patients with locally advanced larynx cancer. J Clin Oncol 2013;31(7):845-52.
Pointreau Y, Garaud P, Chapet S, et al. Randomized trial of induction chemotherapy with cisplatin and 5-fluorouracil with or without docetaxel for larynx preservation. J Natl Cancer Inst 2009;101(7):498-506.
Posner MR, Norris CM, Wirth LJ, et al. Sequential therapy for the locally advanced larynx and hypopharynx cancer subgroup in TAX 324: survival, surgery, and organ preservation. Ann Oncol 2009;20(5):921-7.
NCCN Guidelines 2020 of head and neck cancer.
Adelstein DJ, Li Y, Adams GL, et al. An intergroup phase III comparison of standard radiation therapy and two schedules of concurrent chemoradiotherapy in patients with unresectable squamous cell head and neck cancer. J Clin Oncol 2003;21(1):92-8.
Pignon JP, le Maître A, Maillard E, Bet al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol 2009;92(1):4-14.
Seiwert TY. Salama JK Vokes EE. The concurrent chemoradiation paradigm--general principles. Nat Clin Pract Oncol 2007;4(2):86-100.
Gupta T, Agarwal JP, Ghosh-Laskar S, 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.
Vermorken JB, Remenar E, Van Herpen C, et al. Standard cisplatin/infusional 5-fluorouracil (PF) vs docetaxel (T) plus PF (TPF) as neoadjuvant chemotherapy for nonresectable locally advanced squamous cell carcinoma of the head andneck (LA-SCCHN): a phase III trial of the EORTC Head and Neck Cancer Group (EORTC# 24971). J Clin Oncol 2004;22(14_Suppl):5508.
Kim R, Hahn S, Shin J, et al. The effect of induction chemotherapy using docetaxel, cisplatin, and fluorouracil on survival in locally advanced head and neck squamous cell carcinoma: a meta-analysis. Cancer Res Treat 2016;48(3):907-16.
Bonomo P, Livi L. De-intensification for HPV positive oropharyngeal cancer: and yet it moves!: 2019 in review. Clin Transl Radiat Oncol 2020;22:40-43.
Meulemans J, Debacker J, Demarsin H, et al. Oncologic outcomes after salvage laryngectomy for squamous cell carcinoma of the larynx and hypopharynx: a multicenter retrospective cohort study. Ann Surg Oncol 2021;28(3):1751-61.
Cohen EE, Haraf DJ, Kunnavakkam R, et al. Epidermal growth factor receptor inhibitor gefitinib added to chemoradiotherapy in locally advanced head and neck cancer. J Clin Oncol 2010;28(20):3336-43.