A prospective, randomized, multi-center trial to investigate Actovegin in prevention and treatment of acute oral mucositis caused by chemoradiotherapy for nasopharyngeal carcinoma

doi:10.1016/j.radonc.2010.08.003

Radiotherapy and Oncology

Volume 97, Issue 1, October 2010, Pages 113-118

https://doi.org/10.1016/j.radonc.2010.08.003 Get rights and content

Abstract

Purpose

A multi-center prospective randomized trial was conducted to evaluate the efficacy and safety of Actovegin in the prevention and treatment of chemoradiotherapy-induced acute oral mucositis.

Methods and materials

Between February 2006 and May 2007, 156 evaluable patients with nasopharyngeal carcinoma were randomized to Group 1 (n = 53) for prevention, Group 2 (n = 51) for treatment, and Group 3 (n = 52) for control. All patients received concomitant chemoradiotherapy ± induction chemotherapy. Radiation technique and dose were similar among 3 groups. Intravenous Actovegin of 30 ml daily (5 days/week) was administrated from day 1 of the radiotherapy for Group 1 and from the onset of grade 2 mucositis for Group 2, until the end of the radiotherapy.

Results

The incidence of grade 3 mucositis was lower in Group 1 compared with Group 3 (26.4% vs. 55.8%, P = 0.002). Group 2 had a lower progression rate of mucositis from grade 2 to 3 compared with Group 3 (39.2% vs. 60.4%, P = 0.035). There was no difference in the onset time of grade 3 mucositis among 3 groups. Actovegin was well tolerated and no treatment-related adverse events were observed.

Conclusions

Actovegin is effective in the prevention and treatment of chemoradiotherapy-induced oral mucositis.

Section snippets

Eligibility criteria

Eligibility criteria for this study included the following: patients with newly diagnosed stage III–IVB (UICC 2002 staging criteria) NPC scheduled for CRT, age 18–70 years, a Karnofsky performance score ⩾ 70, no significant oral disease, and normal cardiac, hepatic, renal, and hematopoietic functions. Pretreatment evaluation included a complete history and physical examination, complete blood count, and blood chemistry analysis. Staging evaluations included a CT scan or MRI of the nasopharynx and

Results

A total of 160 patients at 4 participating treatment centers entered into the trial and were randomized into Group 1 (n = 53), Group 2 (n = 55) and Group 3 (n = 52) between February 2006 and May 2007. Four patients in Group 2 were considered ineligible for an efficacy analysis. Of these 4 patients, 2 withdrew from study at their request after the first or the third dose of Actovegin, another 2 did not have oral mucositis ⩾ grade 2 during chemoradiotherapy and hence Actovegin was not administered.

Discussion

Oral mucosa is composed of stratified squamous epithelia that are renewed quickly and are highly sensitive to irradiation. Radiotherapy often causes oral acute mucositis characterized by oral erythema, pseudomembrane, necrosis/ulceration, and pain. Acute mucositis is thought to be a complex biologic process, involving direct damage to the dividing cells of the oral epithelium with the depletion of the basal epithelium and inhibition of the proliferation of transit cells [15], [16].

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Conclusions

In summary, our results show that intravenous Actovegin is effective in the prevention and treatment of oral mucositis induced by CRT. Actovegin reduces the severity of oral mucositis and decreases the incidence of severe pain. The efficacy of preventive application appears to be better than therapeutic application.

Conflict of interest statement

The authors claimed no conflict of interest in relation to this manuscript.

Acknowledgements

We thank Nycomed China Limited to provide the study drug Actovegin, and Daniel T.T. Chua, F.R.C.R., Departments of Clinical Oncology, University of Hong Kong, Queen Mary Hospital, Hong Kong SAR, China, for his assistance in English editing and recommendations.

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Phase III randomised trialA prospective, randomized, multi-center trial to investigate Actovegin in prevention and treatment of acute oral mucositis caused by chemoradiotherapy for nasopharyngeal carcinoma

Abstract

Purpose

Methods and materials

Results

Conclusions

Section snippets

Eligibility criteria

Results

Discussion

Conclusions

Conflict of interest statement

Acknowledgements

Int J Radiat Oncol Biol Phys

Radiother Oncol

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Oral Oncol

Oral Oncol

Ann Oncol

Radiother Oncol

Int J Radiat Oncol Biol Phys

Oral Surg Oral Med Oral Pathol

Accelerated superfractionated irradiation for advanced carcinoma of head and neck: concomitant boost technique

Int J Radiat Oncol Biol Phys

Combined chemotherapy and radiation therapy in advanced inoperable squamous cell carcinoma of the head and neck: the final report of a randomized trial

Cancer

Placebo controlled randomized trial of infusion flourouracil during standard radiotherapy in locally advanced head and neck cancer

J Clin Oncol

Randomized comparison of neoadjuvant cisplatin and fluorouracil infusion followed by radiation versus concomitant treatment in advanced head and neck cancer

J Clin Oncol

Quality of life and performance in advanced head and neck cancer patients on concomitant chemoradiotherapy: a prospective examination

J Clin Oncol

Clinical predictors of quality of life in patients with head and neck cancer

Arch Otolaryngol Head Neck Surg

Clinical experiences with treatment of ulcus cruris

Fortsch Med

Clinical study of the effect of Actovegin in the prevention of acute irradiation oropharyngeal mucositis

J Pract Stomatol

Self-report scales and procedures for assessing pain in adults

Phase III randomised trial
A prospective, randomized, multi-center trial to investigate Actovegin in prevention and treatment of acute oral mucositis caused by chemoradiotherapy for nasopharyngeal carcinoma