Clinical Effect of Biafine in Preventing and Treating Radioactive Skin Destruction of Nasopharyngeal Carcinoma Patients Caused by Concurrent Intensity-Modulated Radiotherapy and Chemotherapy

Discussion

There is a high risk for NPC in China and countries of south-eastern Asia, with radiotherapy being the treatment of choice^[4]. In the past, the shortcomings of conventional radiotherapy for NPC include the following: ①a high dose and too large of an irradiated volume; ②an inhomogeneous distribution of the dose at the target site; ③it is difficult to enhance the dose at the target site, which prevents an increase in the local control rate; ④a dose overlapping or gap at the junction between the neighboring fields; ⑤an exorbitant dose to normal tissues and critical organs, and ⑥a conspicuous tissue reaction in the morning and evening.

As a new technology, the IMRT technique attains a concordance between a uniform high-dose 3D area and the target site. Moreover, different doses of irradiation can be given at different target sites, and its advantage lies in the ability to treat complicated clinical foci. Concomitant boosts of irradiation area are permitted, which can produce the effects of a synchronal accelerated modulation radiotherapy. With the same treatment frequency, different doses were given in various related target sites. It has been confirmed by several studies from China and overseas^[9,10] that with conformal IMRT of NPC, one can raise the irradiation dose to the tumor, reduce injury at peripheral normal tissues, enhance the local control rate and attain an improvement in the patient’s quality of life. Previous reports showed that^[11] up to September 30, 2006, there were 52 hospitals in China, including 115 IMRT clinics and departments, which provided radiotherapy. Use of IMRT has gradually increased in clinical practice in China.

The radiotherapeutic target sites for NPC include the nasopharynx and drainage area of the neck lymph node. With an increase in the radiation dose, injury on the skin will become more severe, resulting in a failure of dermal basal cells to produce new cells, and a loss of mature epithelial cells. If the desquamated surface is not replenished rapidly enough, skin destruction (SD) will occur. At the same time, the incidence of radiodermatitis will be high, because the neck skin is tender and is frequently affected by friction of the fixed face guard during the course of radiotherapy. Following concomitant chemotherapy and radiotherapy, the incidence of radiodermatitis will rise and the reaction enhanced. So, under these conditions the radiotherapy is usually suspended, and symptomatic treatments applied, such as taking a rest and providing anti-inflammatory treatment etc. The biologic effects of radiotherapy are decreased which adds new suffering to the patients, affects their quality of life, and even more has an impact on survival rate and time of tumor management, resulting in a decrease in the curative effect of local control of the tumor.

Over the past few years, several topical remedies have shown to lessen the symptoms of radiodermatitis. These drugs include the following: an epidermal growth factor preparation, antibacterial agents (i.e. sulfadiazine), hormones, vitamins, and Chinese herbal drugs etc.^[12] It has been clear, following retrieval of the literature on radiation-induced toxicity, that there is no general standard therapeutic regimen for preventing irradiation-evoked dermal toxicity^[12]. Therefore, the treatment methods for controlling this dermal toxicity can only be derived from clinical experience, and a physician’s propensity to use topical remedies.

Since 1976, Biafine has been used to treat radiodermatitis^[13], and since then this drug is being used more and more in cancer radiotherapy centers. Biafine is a water-based cream which was developed and produced by the French Medix drug company. It can quicken skin wound healing and relieve radiodermatitis symptoms^[14]. The process of Biafine production includes both an aqueous and oil phase. The aqueous phase contains demineralized water (75.5%), algin (0.70%) and triethanolamine (TEA) (67%). The antiseptic agents include potassium sorbate (10%), sodium methyl hydroxybenzoate (0.1%), sodium propyl methyl hydroxybenzoate (0.05%) and stearic acid TEA. The oil phase contains liquid paraffin (6.85%), ethylene-glycol stearate (3.63%), propylene glycol (2.3%), solid paraffin (1.6%), squalene (1.5%), avocado oil (1.0%), palmitic acid hexadecanol-ester (0.35%) and aromatic spices (0.13%).

Biafine deeply moisturizes the skin, and provides a good environment for dermal self-renovation. Its dual effects of cleaning and drainage can increase the skin blood flow rate to remove exudate, to improve dermal metabolism, to replenish the desquamated epidermal cells, and to promote regeneration and replenishment of the impaired cells. It also alters the ratio between interleukin 1 and interleukin 6, to stimulate fibroblast proliferation and to increase collagenic synthesis. In addition, Biafine is not greasy, is convenient to use and washes off without an uncomfortable feeling.

Several papers related to the application of Biafine and the prevention of radiodermatitis have been pub-lished in China. For instance, Sun et al.^[15] reported that the incidence of skin reactions was respectively 93.8% and 30.4% in a control group and a medicated group (Biafine group). Low-grade radiation reactions, i.e., degree-I and II were 66.7% (32/48 cases) and 28.6% (16/56 cases) in the control and the medicated groups. It was reported in other studies^[16] that in 41 cases of a Biafine-treated group, acute degree-I radioactive skin reaction was found in 9, and degree-II in 32. No reaction of degree-III or above was found in the group. In 40 cases of the control group, a degree-I reaction was found in 3 and degree-II in 28. In 9 of these 40 cases, the therapy was discontinued for 7 to 13 days, owing to a reaction of degree-III or over degree-III. After the Ridit analysis, there was a statistical significance between the two groups (P<0.01). It was reported by Wu and Zhu^[17] that the incidence of acute degree-I radioactive injury on the skin of neck was 62.5% (15/24 cases) and 33.3% (9/27 cases) respectively in a medicated and control group. The incidence of a degree-II reaction was 25.0% (6/24 cases) and 44.4% (12/27 cases) respectively in the medicated and the control group, while the incidence of degree-III injury was 12.5 % (3/24 cases) in the treated group and 22.3 % (6/27 cases) in the control group. Among the above, there was a significant difference in the extent of degree-I radioactive dermal injury between the two groups (P<0.05).

For the patients in our study, the incidence of skin reactions was 100%. However, the severity was obvi-ously lower in the Biafine-treated group compared to the control group (P=0.01). The incidence of slight radiation reactions (degree-I plus II) was 88.0% (22/25 cases) and 57.7% (15/26 cases) respectively in the medicated and control groups, and degree-III radiation reactions occurred in 12.0% (3/25 cases) of the patients in the treated group and 42.3% (11/26 cases) in the control group. These results might be in contrast to the literature, probably because of a very high radiation dose to neck and joint chemotherapy. A severe radiation reaction (wet reaction) occurred in 3 cases of the medicated group. Exudation decreased at day 1 after medication, and incrustation formed and pain vanished at day 3. At day 5 or day 6 following the medication, decrustation occurred and fresh skin emerged. In the cases of the medicated group, no discontinuance of radiotherapy was required. In the control group, severe radiation reactions (wet reaction) were present in 11 cases. In 6 of the 11 cases, radiotherapy was suspended, debridement and a change of dressing, as well as herbal hydropathic compress were applied, with high-flow oxygen therapy on the destroyed skin and general administration of antibiotics. The patients receiving the therapy and antibiotics fully recovered 1 or 2 weeks later. In our group, the effect of Biafine cream indicated that the onset of skin reactions in the NPC patients receiving concomitant radiotherapy and chemotherapy was delayed compared to the control group, and only acute degree-I and II radioactive SD occurred on the neck of most patients. Application of Biafine can accelerate healing of degree-III skin reactions and lessen the patient’s pain.

Previously it was reported^[17] that skin reactions occurred in 29.4% (5/17) of a Biafine-treated group of patients and 91.1% (41/45) in the controls before reaching 40 Gy of irradiation. In our study, the reactions occurred in 32.0% (8/25) of the medicated group and 96.2% (25/26) of the controls before a dose of 40 Gy, P<0.001, results which were close to the reports from the literature. These findings showed that application of the Biafine cream delayed the emergence of acute radioactive SD, and radioactive SD was not aggravated following the adjuvant chemotherapy. Moreover, when Biafine cream was used, the toxic reaction was not found in all patients of the medicated group. During the whole period of radiotherapy, the patients could engage in some physical activities such as neck revolution etc., after applying Biafine cream. These activities played an important role in lightening the post-radiotherapeutic fibrosis and sclerosis of the neck, thus improving the patients’ quality of life. So, after radiotherapy and chemotherapy, Biafine cream should be applied on the first day to protect the NPC patient’s skin, until end of the radiotherapy. It can enhance the tolerance of the patient’s skin, postpone the radiotherapy-induced skin reaction, and can decrease the degree of the reaction. The cream can effectively treat and prevent the degree-I, II and III radioactive SD, and aid in the smooth proceeding of radiotherapy.

In summary, following application of the Biafine cream, a degree-I or II radiodermatitis occurs in most of the NPC patients receiving concomitant chemotherapy with radiotherapy. However, when Biafine is used, the toxicity to the skin will not prolong the time of therapy or require the treatment to cease. Our prospective study shows that prophylaxis with Biafine for radioactive dermatofibrosis delayed the time of emergence of radioactive dermatofibrosis. Use of this cream should be practiced along with concurrent chemotherapy and radiotherapy.