CHRONOMODULATED APPROACH TO CHEMORADIOTHERAPY OF LOCALLY ADVANCED HEAD AND NECK CANCER

Introduction. The standard treatment for patients with inoperable locally advanced head and neck cancer is chemoradiotherapy with cisplatin. The high toxicity of this method doesn’t allow it to be used with 30,0 % of patients, namely patients older than 70 years, with low somatic status. One of the ways to increase the efficiency and reduce toxicity is the use of chemomodifiers in the chronomodulated mode in combination with non-standard dose fractionation regimes.

The aim of the study. To analyze the effectiveness of different methods of chemoradiation treatment and their toxicity in the treatment of locally advanced squamous cell carcinoma of the head and neck.

Methods. Within the confines of a randomized controlled trial authors presents own clinical observations of 73 patients for the period fr om 2012 to 2016 in SI “Grigoriev Institute for Medical Radiology of NAMS of Ukraine”. Patients were divided into two groups: 39 patients were treated using the developed methodology of chronomodulated radiotherapy with 5-fluorouracil in the dose hypofractionation mode; 34 patients received chemoradiotherapy with cisplatin in the classical regime. The criterion for inclusion in the study was exclusively voluntary informed consent of the patient; exclusion from the study was carried out in the event of the patient's refusal to continue to participate in the study at any stage. In the course of the study clinical, biochemical, immunoenzymatic, and radiological methods of examination were used. Statistical processing of the data was carried out using the "STATISTICA 12" software package.

Results. The regimen of chronomodulated radiotherapy with 5-fluorouracil and chemoradiation treatment with cisplatin were almost equal in effectiveness (complete and partial tumor response), namely 77,0 and 73,5%, respectively (p=0,35). The two-year survival rate was (46,2±8,0) and (38,2±8,3)%, respectively (p=0,25). When comparing survival curves by the Kaplan-Meier log-rank method, the criterion was – 0,710953, p=0,47711, which indicates the comparability of the effectiveness of the two comparable chemoradiation treatment regimens.

Grade 3 mucositis was registered in 14 (35,9%) patients of the first group and 14 (41,2%) patients of the second group (p=0,32). In 2 (5,9 %) patients receiving cisplatin, Grade 4 mucositis was registered, which required urgent hospitalization, parenteral nutrition for 5-8 days, and injection therapy.

A general grade 2-3 weakness was noted in 23,1% of patients treated with 5-fluorouracil, compared with 61,8% with cisplatin (p=0,0004). Also, the incidence of nausea and vomiting was higher after administration of cisplatin and amounted to 58,8 and 23,5%, compared with 5,1 and 2,6%, in patients’ groups respectively (p<0,0001).

The development of grade 1 leukopenia was noted in 8 (20,5 %) of 39 patients receiving radiotherapy with chronomodulated administration of 5-fluorouracil, and in 18 (52,9%) of 34 patients wh ere as the chemomodifier was used cisplatin (p=0,0001).

Conclusions. When analyzing the immediate and the nearest long-term results of treatment of patients with locally advanced squamous cell carcinoma of the head and neck, there was no significant difference in the application of the developed method of chronomodulated radiotherapy with 5-fluorouracil in a hypofractionation mode compared to conventional chemoradiation therapy with cisplatin. The high toxicity of cisplatin in contrast to 5-fluorouracil dictates the advisability of using the latter in the treatment of elderly patients and patients with low somatic status.

Keywords: head and neck cancer, chronomodulated therapy, hypofraction, chemoradiotherapy, radiation toxicity.


Sergii V. Artiukh, Olena M. Sukhina, Victor P. Starenkiy

 

Grigoriev Institute for Medical Radiology of National Academy of Medical Sciences of Ukraine, Kharkov, Ukraine

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Библиографическая ссылка:

Артюх С.В., Сухина Е.Н., Старенький В.П. Хрономодулированный подход к радиохимиотерапии местнораспространенного рака головы и шеи / / Наука и Здравоохранение. 2018. 3 (Т.20). С. 20-31.

Artiukh S.V., Sukhina O.M., Starenkiy V.P. Chronomodulated approach to chemoradiotherapy of locally advanced head and neck cancer. Nauka i Zdravookhranenie [Science & Healthcare]. 2018, (Vol.20) 3, pp. 20-31.

Артюх С.В., Сухина Е.Н., Старенький В.П. Бас және мойын жергілікті таралған обырының радиохимиотерапиясына хрономодулденген әдісі / / Ғылым және Денсаулық сақтау. 2018. 3 (Т.20). Б. 20-31.