Treatment of radiation- and chemotherapy-induced stomatitis SHIRLEY B. CARNEL, MAJ MC, DON B. BLAKESLEE, LTC MC, STEPHEN G. OSWALD, MAJ MC, and MARGARET BARNES, MD, Aurora, Colorado, and Philadelphia, Pennsylvania
Severe stomatitis is a common problem encountered during either radiation therapy or chemotherapy. Most therapeutic regimens are empirical, with no scientific basis. The purpose of this study is to determine the efficacy of various topical solutions in the treatment of radiation- or chemotherapy-induced stomatitis. Eighteen patients were entered into a prospective double-blinded study to test several topical solutions: (1) viscous lidocaine with 1% cocaine; (2) dyclonine hydrochloride 1.0% (Dyclone); (3) kaolin-pectin solution, diphenhydramine plus saline (KBS); and (4) a placebo solution. Degree of pain relief, duration of relief, side effects, and palatability were evaluated. The results showed that Dyclone provided the most pain relief. Dyclone and viscous lidocaine with 1% cocaine provided the longest pain relief, which averaged 50 minutes This study provides objective data and defines useful guidelines for treatment Of Stomatitis. [OTOLARYNGOL HEAD NECK SURG 1990:102:326.1
S e v e r e stomatitis is a common problem encounterd during either radiation therapy or chemotherapy, particularly with agents such as methotrexate, actinomycin-D, and 5-fluorouracil. Symptoms of this problem include pain and swallowing difficulties that significantly interfere with nutrition. Stomatitis as a complication of radiation and chemotherapy is frequently mentioned in the literature; however, specific treatment protocols and their effectiveness have received only superficial attention. ’.’ Therapeutic regimens are often empirical, with no scientific basis. Typical regimens recommend maintenance of oral hygiene, with frequent gentle debridement using a mixture of salt and baking soda, artificial saliva to maintain lubrication, and topical anesthetics if severe pain is present.
~
From the Department of Otolaryngoloyg-Head and Neck Surgery Service (Drs. Camel and Blakeslee) and Hematology/ Oncology Service (Dr. Oswald), Fitzsimons Army Medical Center, and the Radiation Therapy Department, Fox Chase Cancer Center (Dr. Barnes). The opinions contained herein are the private views of the authors and do not purport to reflect the position of the Department of the Army or the Department of Defense. Presented at the Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery, Washington, D.C., Sept. 25-29, 1988. Submitted for publication Nov. 3, 1988; revision received June 26, 1989; accepted Sept. 20, 1989. Reprint requests: Don B. Blakeslee, LTC MC, Otolaryngology-Head and Neck Surgery Service, Fitzsimons Army Medical Center, Aurora, CO 80045-5000. 2311116913
The purpose of this study is to determine the efficacy of various topical solutions in the treatment of radiationor chemotherapy-induced stomatitis. METHODS AND MATERIALS
This study was conducted by the OtolaryngologyHead and Neck Surgery Service at Fitzsimons Army Medical Center in Aurora, Colorado, between January 1984 and December 1986. Patients were entered into a prospective double-blinded study to test the efficacy of several commonly prescribed topical solutions. The solutions tested included: (1) viscous lidocaine with 1% cocaine; (2) dyclonine hydrochloride I .O% (Dyclone, Astra Pharmaceutical Products, Inc., Westborough, Mass.); (3) a mixture of kaolin-pectin solution, diphenhydramine plus saline (KBS) in a ratio of 1 : 1 : 1 ; and (4) a placebo solution. Viscous lidocaine with 1% cocaine was chosen because a comparison study by Artim et al.4 indicated viscous lidocaine alone was less efficacious. The mixture of lidocaine and cocaine was prepared in the inpatient pharmacy at Fitzsimons. Handling and control were closely monitored by the ward nursing staff. Patients being treated with chemotherapy or radiation therapy were interviewed and evaluated during their treatment programs to determine the presence of stomatitis. Patient selection was made on the basis of following criteria: (1) patients in whom stomatitis developed because of either radiation therapy or chemotherapy during treatment of malignant disease; (2) patients with moderately severe stomatitis that interfered with ingestion of food or fluids; (3) patients who would be reasonably able to quantify and describe the seventy of
326
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
Volume 102 Number 4 April 1990
Radiation- and chemotherapy-inducedstomatitis 327
Topical Solutions for Stomatitis Patient: Diagnosis: Age: Sex: Cause of stomatitis: Day 1 Date: Drug code: Did the medication relieve the discomfort in your mouth? Yes No If 'Yes', to what degree? Minimal relief Moderate relief Complete relief How long did the relief seem to last? Number of doses? Did you experience any side effects or reactions to the medications? No Yes If 'Yes', please describe them:
Fig. 1. Report form used by patients to document results of treatment.
local symptoms; and (4) patients who could administer medication without direct supervision. Patients participating in the study were thoroughly counseled and asked to sign an informed consent approved by the Clinical Investigation Committee. The treatment schedule had two study arms. Arm 1 included patients who were given a different mixture each day for 4 consecutive days. The patient was instructed to either gargle the solution and expectorate or apply it directly to any lesions about the oropharynx with a gauze sponge. Since the medication was available at the bedside, the patient self-administered it as frequently as needed for pain relief. The contents of each day's dose was unknown to either the patient or the observer. The order in which the drugs were given was random and established by the pharmacist. Each morning a new vial was delivered to the patient along with a report (Fig. 1) that required the patient to document the results of the previous day's treatment. If the patient experienced undue side effects, the medication was stopped immediately. Vital signs included temperature, pulse, and blood pressure four times per day during the study period. Fungal cultures were obtained before treatment to identify candida infections. Arm 2 of the treatment schedule included patients who had stomatitis that extended beyond the 4-day trial period of Arm 1. The topical solution that was most effective for these patients was continued on a daily basis for as long as necessary.
RESULTS Eighteen patients participated in the prospective double-blinded study after signing the consent form. Fourteen patients completed the study. Two patients were excluded because of noncompliance and two others failed to complete the questionnaire. The cause of stomatitis was radiation therapy in seven patients and to chemotherapy in the remaining seven. The degree of pain relief was graded by the patients and ranged from no relief (0)to complete relief ( 3 ) . The mean score for each medication was compared. The results were as follows: Dyclone was considered the best medication for pain relief (Fig. 2); the placebo solution had a minimal effect and did not fare as well as the medicated solutions. Most of the patients commented that the special attention given them was appreciated. The duration of relief (Fig. 3) was approximately 50 minutes for both Dyclone and the viscous lidocaine with 1% cocaine. Suprisingly, the placebo solution and the KBS solution were nearly equal when duration of relief was compared. Their effects lasted approximately 35 minutes. No statistical difference was found among the four solutions when pain relief ( p = 0.7334) and duration of relief ( p = 0.4673) were compared on the basis of a one-way analysis of variance (ANOVA). No significant side effects occurred. The Dyclone was the least palatable. The patients preferred the method of self-ministration. No problems were encountered with substance control because the amount
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
328
OtolaryngologyHead and Neck Surgery
CARNEL et a1
3
2
.-
m
z
2
-E
a, a,
70 3
z 1
E,
E ._ c ._ I 0
Dyclone
Lidocaine
KBS
Placebo
1% Cocaine
Solution Fig. 2. Results and comparison of various medication treatments used in study.
of each solution at the bedside was well below a toxic dose if accidentally ingested. DISCUSSION Head and neck cancer patients are frequently treated with either radiation therapy or chemotherapy or both. These treatment modalities are used as either primary or adjunctive therapies and can potentially be devastating to the patients’ physical and psychologic condition. The otolaryngologist-head and neck surgeon must be aware of the potential side-effects and be prepared to effectively combat them. A plethora of oral complications exist, including stomatitis, hemorrhage, xerostomia, trismus, radiation caries, osteoradionecrosis, infection, and poor nutrition. Stomatitis is reported consistently by patients undergoing radiation therapy and treatment with cytotoxic agents, such as the antimetabolites (methotrexate, 5-flourouracil) and the antitumor antibiotics (actinomycin-D, adriamycin, bleomycin, daunorubicin, and mithramycin). The oral pain often precludes adequate nutritional intake and complicates an already difficult therapeutic plan. A brief review of the chemotherapeutic agents used in this study helps explain the complication of stomatitis. The cytotoxic agents primarily exert their major effects against dividing cells. Unfortunately, oral mucosa consists of rapidly dividing tissue and is especially prone to toxic effects. As a group, the antitumor antibiotics exhibit the most characteristic effects on mucous membranes. Methotrexate, an antimetabolite fo-
late antagonist, causes significant mucosal ulceration, especially when given in high doses, despite adequate folinic acid rescue.’ The mucocutaneous reaction pattern in patients who receive chemotherapy is variable and demands careful clinical evaluation. The differential diagnosis must include these few antineoplastic agents that cause mucocutaneous eruption in order to avoid unnecessary clinical or laboratory investigation. If chemotherapeutic agents are used several weeks after radiation therapy, the clinician must be aware of the radiation recall effect. Adriamycin and actinomycin-D are the most common agents responsible for enhancing the radiation effects. The skin and oral mucosa are most sensitive to the interactive damage of chemotherapy-radiation combination.6 In contrast, stomatitis induced by radiation therapy alone is more predictable and has been intensively studied. Again, a brief review will help explain the complication of radiation-induced stomatitis. Coutard7 is credited with the earliest and most classic description of radioepithelitis of the oropharyngeal region. Radiomucositis in normal tissue is a problem that can be divided into clinical periods: acute, subacute (1 year), chronic (1 to 5 years), and late ( 5 years and longer).8 The present study focuses on treatment during the acute clinic period (Table 1). Soreness, dysphagia, and dryness of the oral mucosa begins during the second week (2000 to 2400 rad) of radiation therapy. The palate and uvula are the first areas of the oral cavity in which definite erythema and patchy mucositis develop. During
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
Volume 102 Number 4 April 1990
Radiation- and chemotherapy-induced stomatitis 329
60
/
45 v) Q)
-
U
3
.-C
30
z
15
0 Dyclone
Lidocaine 1% Cocaine
Placebo
KBS
Solution Fig. 3. Results and comparison of duration of relief provided by various medication treatments used in study.
Table 1. Acute clinical period in oral cavity caused by irradiation Week
Rod level
Symptoms
Sign
1 2
1000-1200 2000-2400
3
3000-3600
4
4000-4800
No significant complaints Soreness, dryness dysphagia, loss of appetite Swollen tongue, parched mouth, thickened saliva Complaints intensify
5
5000-6000
Prominence of circumvallate papillae Erythema, patchy mucositis of palate and uvula Mucositis extends onto tonsillar pillars Progressive involvement to buccal rnucosa Confluent white-to-yellow pseudomembrane extending to tongue
i
Nutrition difficulty due to severity of reaction
the fifth week (5000 to 6000 rad), the greatest reaction occurs and nutrition is most difficult. A yellow-to-white pseudomembrane covers the field of radiation (Fig. 4) and includes the tongue, which is the last site in which mucositis develops. Radiation epithelitis usually clears in 2 to 4 weeks and the healing phase is complete 1 to 2 months after treatment ends. Treatment of oral stomatitis induced by radiation therapy or chemotherapy or both is primarily symptomatic and empirical. Infection is commonly encountered and must be treated with excellent oral hygiene. Daily oral pressure sprays aid healing by removal of impacted debris from necrotic tissue. Cultures often reveal oral candidiasis (thrush); the primary agent of choice is nystatin oral suspension (100,000 units/ml), which is taken orally as a 5-ml dose four times per day for 1 to
2 weeks. The nystatin is gargled for several minutes before swallowing. Ketoconazole is the preferred alternative and is taken orally as a 200-mg dose once a day for 1 to 2 weeks. All patients in this study were cultured and treated for candidiasis before the administration of the oral medications. Dyclone provided the best pain control, but was the least palatable. This solution is a ketone and a separate class of topical anesthetic. Dyclone effects surface anesthesia when applied to the mucous membrane. The mechanism of action is unknown. The next best solution was viscous lidocaine with 1% cocaine. Both solutions produced topical anesthesia and were allowed to coat the oral mucosa. No food or drink were taken for at least 15 minutes, in order for the medication to be effective; otherwise, the coating effect was washed
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
330
OtolaryngologyHead and Neck Surgery
CARNEL et al
Fig. 4. Photograph of pseudomembrane covering the field of radiation on the tongue.
away. The medications were swallowed or swished, depending upon the extent of the stomatitis. As previously indicated, swallowing may be difficult for some patients, but, if an explanation is given, aspiration is generally not a problem. This technique is used shortly before meals and helps maintain adequate nutrition. The anesthetic effect of the medications is not a contraindication for use at mealtime if used cautiously. Although not studied in this project, diet is mentioned for completeness. A semisolid-to-liquid diet is best tolerated. Baby foods, breakfast drinks, and vitamins are excellent supplements. Enteral hyperalimentation with commercially prepared products work extremely well if swallowing is temporarily interrupted. Diversions such as esophagectomy or gastrostomy are indicated for extensive oropharyngeal disease. Avoidance measures aid in the treatment of stomatitis. Alcohol, tobacco, or spicy foods intensify the reaction of the oral mucosa. Many commercial mouth lozenges and mouthwashes contain alcohol, which should be avoided. Aspirin causes acidification of the oral cavity and also may intensify the pain locally. Many medicated solutions have been recommended for the treatment of stomatitis, including dilute hydrogen peroxide (1 :3), five percent bicarbonate of soda, spray solution of pontocaine 0.5 percent, and viscous lidocaine. The list is long, allowing the physician or nurse a varied selection. As the intensity of pain increases, systemic oral analgesics are preferred over the
topical medications. This pilot study suggests guidelines for the use of three oral medications. The sample size is too small to draw definite conclusions. Further studies are indicated to better define the effectiveness of the many oral solutions available for the treatment of stomatitis induced by radiation therapy or chemotherapy or both. W e wish t o thank Troy H. Patience, BS, who acted as the statistician consultant, and Mrs. Pat Perez, who helped in the preparation of the manuscript. REFERENCES
1. Braham RL. Intra-oral problems associated with head and neck
2. 3.
4.
5. 6.
7.
8.
irradiation for malignant disease in children and adolescents. Practitioner 1981;225: 1309- 14. Adrian RM, Hood AF, Skarin A. Complications of chemotherapeutic agents. CA 1980;30;143-57. Schaaf JE. Dealing with oral complications in irradiated cancer patients. Alurni Bulletin IUND 1982;(Spring): 14-7. Artirn R, DiBella N, Bourg W. Relief of antineoplastic therapyinduced stomatitis pain with low concentration topical cocaine. Proceedings ASCO 1983;2:93. Weinstein GD. Methotrexate. Ann Intern Med 1977;86:199-204. Phillips TL, Fu KK. Quantification of combined radiation therapy and chemotherapy effects on critical normal tissue. Cancer 1976;37;1186- 1200. Coutard H. Roentgen therapy of epitheliomas of tonsillar regions, hypopharynx, and larynx, from 1920 to 1926. Am J Roentgenol 1932;28:313-31. Rubin P, Casarett GW. Clinical radiation pathology. 1st ed. Philadelphia: WB Saunders Co., 1968;121-51.
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
Severe stomatitis is a common problem encountered during either radiation therapy or chemotherapy. Most therapeutic regimens are empirical, with no scientific basis. The purpose of this study is to determine the efficacy of various topical solutions in the treatment of radiation- or chemotherapy-induced stomatitis. Eighteen patients were entered into a prospective double-blinded study to test several topical solutions: (1) viscous lidocaine with 1% cocaine; (2) dyclonine hydrochloride 1.0% (Dyclone); (3) kaolin-pectin solution, diphenhydramine plus saline (KBS); and (4) a placebo solution. Degree of pain relief, duration of relief, side effects, and palatability were evaluated. The results showed that Dyclone provided the most pain relief. Dyclone and viscous lidocaine with 1% cocaine provided the longest pain relief, which averaged 50 minutes This study provides objective data and defines useful guidelines for treatment Of Stomatitis. [OTOLARYNGOL HEAD NECK SURG 1990:102:326.1
S e v e r e stomatitis is a common problem encounterd during either radiation therapy or chemotherapy, particularly with agents such as methotrexate, actinomycin-D, and 5-fluorouracil. Symptoms of this problem include pain and swallowing difficulties that significantly interfere with nutrition. Stomatitis as a complication of radiation and chemotherapy is frequently mentioned in the literature; however, specific treatment protocols and their effectiveness have received only superficial attention. ’.’ Therapeutic regimens are often empirical, with no scientific basis. Typical regimens recommend maintenance of oral hygiene, with frequent gentle debridement using a mixture of salt and baking soda, artificial saliva to maintain lubrication, and topical anesthetics if severe pain is present.
~
From the Department of Otolaryngoloyg-Head and Neck Surgery Service (Drs. Camel and Blakeslee) and Hematology/ Oncology Service (Dr. Oswald), Fitzsimons Army Medical Center, and the Radiation Therapy Department, Fox Chase Cancer Center (Dr. Barnes). The opinions contained herein are the private views of the authors and do not purport to reflect the position of the Department of the Army or the Department of Defense. Presented at the Annual Meeting of the American Academy of Otolaryngology-Head and Neck Surgery, Washington, D.C., Sept. 25-29, 1988. Submitted for publication Nov. 3, 1988; revision received June 26, 1989; accepted Sept. 20, 1989. Reprint requests: Don B. Blakeslee, LTC MC, Otolaryngology-Head and Neck Surgery Service, Fitzsimons Army Medical Center, Aurora, CO 80045-5000. 2311116913
The purpose of this study is to determine the efficacy of various topical solutions in the treatment of radiationor chemotherapy-induced stomatitis. METHODS AND MATERIALS
This study was conducted by the OtolaryngologyHead and Neck Surgery Service at Fitzsimons Army Medical Center in Aurora, Colorado, between January 1984 and December 1986. Patients were entered into a prospective double-blinded study to test the efficacy of several commonly prescribed topical solutions. The solutions tested included: (1) viscous lidocaine with 1% cocaine; (2) dyclonine hydrochloride I .O% (Dyclone, Astra Pharmaceutical Products, Inc., Westborough, Mass.); (3) a mixture of kaolin-pectin solution, diphenhydramine plus saline (KBS) in a ratio of 1 : 1 : 1 ; and (4) a placebo solution. Viscous lidocaine with 1% cocaine was chosen because a comparison study by Artim et al.4 indicated viscous lidocaine alone was less efficacious. The mixture of lidocaine and cocaine was prepared in the inpatient pharmacy at Fitzsimons. Handling and control were closely monitored by the ward nursing staff. Patients being treated with chemotherapy or radiation therapy were interviewed and evaluated during their treatment programs to determine the presence of stomatitis. Patient selection was made on the basis of following criteria: (1) patients in whom stomatitis developed because of either radiation therapy or chemotherapy during treatment of malignant disease; (2) patients with moderately severe stomatitis that interfered with ingestion of food or fluids; (3) patients who would be reasonably able to quantify and describe the seventy of
326
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
Volume 102 Number 4 April 1990
Radiation- and chemotherapy-inducedstomatitis 327
Topical Solutions for Stomatitis Patient: Diagnosis: Age: Sex: Cause of stomatitis: Day 1 Date: Drug code: Did the medication relieve the discomfort in your mouth? Yes No If 'Yes', to what degree? Minimal relief Moderate relief Complete relief How long did the relief seem to last? Number of doses? Did you experience any side effects or reactions to the medications? No Yes If 'Yes', please describe them:
Fig. 1. Report form used by patients to document results of treatment.
local symptoms; and (4) patients who could administer medication without direct supervision. Patients participating in the study were thoroughly counseled and asked to sign an informed consent approved by the Clinical Investigation Committee. The treatment schedule had two study arms. Arm 1 included patients who were given a different mixture each day for 4 consecutive days. The patient was instructed to either gargle the solution and expectorate or apply it directly to any lesions about the oropharynx with a gauze sponge. Since the medication was available at the bedside, the patient self-administered it as frequently as needed for pain relief. The contents of each day's dose was unknown to either the patient or the observer. The order in which the drugs were given was random and established by the pharmacist. Each morning a new vial was delivered to the patient along with a report (Fig. 1) that required the patient to document the results of the previous day's treatment. If the patient experienced undue side effects, the medication was stopped immediately. Vital signs included temperature, pulse, and blood pressure four times per day during the study period. Fungal cultures were obtained before treatment to identify candida infections. Arm 2 of the treatment schedule included patients who had stomatitis that extended beyond the 4-day trial period of Arm 1. The topical solution that was most effective for these patients was continued on a daily basis for as long as necessary.
RESULTS Eighteen patients participated in the prospective double-blinded study after signing the consent form. Fourteen patients completed the study. Two patients were excluded because of noncompliance and two others failed to complete the questionnaire. The cause of stomatitis was radiation therapy in seven patients and to chemotherapy in the remaining seven. The degree of pain relief was graded by the patients and ranged from no relief (0)to complete relief ( 3 ) . The mean score for each medication was compared. The results were as follows: Dyclone was considered the best medication for pain relief (Fig. 2); the placebo solution had a minimal effect and did not fare as well as the medicated solutions. Most of the patients commented that the special attention given them was appreciated. The duration of relief (Fig. 3) was approximately 50 minutes for both Dyclone and the viscous lidocaine with 1% cocaine. Suprisingly, the placebo solution and the KBS solution were nearly equal when duration of relief was compared. Their effects lasted approximately 35 minutes. No statistical difference was found among the four solutions when pain relief ( p = 0.7334) and duration of relief ( p = 0.4673) were compared on the basis of a one-way analysis of variance (ANOVA). No significant side effects occurred. The Dyclone was the least palatable. The patients preferred the method of self-ministration. No problems were encountered with substance control because the amount
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
328
OtolaryngologyHead and Neck Surgery
CARNEL et a1
3
2
.-
m
z
2
-E
a, a,
70 3
z 1
E,
E ._ c ._ I 0
Dyclone
Lidocaine
KBS
Placebo
1% Cocaine
Solution Fig. 2. Results and comparison of various medication treatments used in study.
of each solution at the bedside was well below a toxic dose if accidentally ingested. DISCUSSION Head and neck cancer patients are frequently treated with either radiation therapy or chemotherapy or both. These treatment modalities are used as either primary or adjunctive therapies and can potentially be devastating to the patients’ physical and psychologic condition. The otolaryngologist-head and neck surgeon must be aware of the potential side-effects and be prepared to effectively combat them. A plethora of oral complications exist, including stomatitis, hemorrhage, xerostomia, trismus, radiation caries, osteoradionecrosis, infection, and poor nutrition. Stomatitis is reported consistently by patients undergoing radiation therapy and treatment with cytotoxic agents, such as the antimetabolites (methotrexate, 5-flourouracil) and the antitumor antibiotics (actinomycin-D, adriamycin, bleomycin, daunorubicin, and mithramycin). The oral pain often precludes adequate nutritional intake and complicates an already difficult therapeutic plan. A brief review of the chemotherapeutic agents used in this study helps explain the complication of stomatitis. The cytotoxic agents primarily exert their major effects against dividing cells. Unfortunately, oral mucosa consists of rapidly dividing tissue and is especially prone to toxic effects. As a group, the antitumor antibiotics exhibit the most characteristic effects on mucous membranes. Methotrexate, an antimetabolite fo-
late antagonist, causes significant mucosal ulceration, especially when given in high doses, despite adequate folinic acid rescue.’ The mucocutaneous reaction pattern in patients who receive chemotherapy is variable and demands careful clinical evaluation. The differential diagnosis must include these few antineoplastic agents that cause mucocutaneous eruption in order to avoid unnecessary clinical or laboratory investigation. If chemotherapeutic agents are used several weeks after radiation therapy, the clinician must be aware of the radiation recall effect. Adriamycin and actinomycin-D are the most common agents responsible for enhancing the radiation effects. The skin and oral mucosa are most sensitive to the interactive damage of chemotherapy-radiation combination.6 In contrast, stomatitis induced by radiation therapy alone is more predictable and has been intensively studied. Again, a brief review will help explain the complication of radiation-induced stomatitis. Coutard7 is credited with the earliest and most classic description of radioepithelitis of the oropharyngeal region. Radiomucositis in normal tissue is a problem that can be divided into clinical periods: acute, subacute (1 year), chronic (1 to 5 years), and late ( 5 years and longer).8 The present study focuses on treatment during the acute clinic period (Table 1). Soreness, dysphagia, and dryness of the oral mucosa begins during the second week (2000 to 2400 rad) of radiation therapy. The palate and uvula are the first areas of the oral cavity in which definite erythema and patchy mucositis develop. During
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
Volume 102 Number 4 April 1990
Radiation- and chemotherapy-induced stomatitis 329
60
/
45 v) Q)
-
U
3
.-C
30
z
15
0 Dyclone
Lidocaine 1% Cocaine
Placebo
KBS
Solution Fig. 3. Results and comparison of duration of relief provided by various medication treatments used in study.
Table 1. Acute clinical period in oral cavity caused by irradiation Week
Rod level
Symptoms
Sign
1 2
1000-1200 2000-2400
3
3000-3600
4
4000-4800
No significant complaints Soreness, dryness dysphagia, loss of appetite Swollen tongue, parched mouth, thickened saliva Complaints intensify
5
5000-6000
Prominence of circumvallate papillae Erythema, patchy mucositis of palate and uvula Mucositis extends onto tonsillar pillars Progressive involvement to buccal rnucosa Confluent white-to-yellow pseudomembrane extending to tongue
i
Nutrition difficulty due to severity of reaction
the fifth week (5000 to 6000 rad), the greatest reaction occurs and nutrition is most difficult. A yellow-to-white pseudomembrane covers the field of radiation (Fig. 4) and includes the tongue, which is the last site in which mucositis develops. Radiation epithelitis usually clears in 2 to 4 weeks and the healing phase is complete 1 to 2 months after treatment ends. Treatment of oral stomatitis induced by radiation therapy or chemotherapy or both is primarily symptomatic and empirical. Infection is commonly encountered and must be treated with excellent oral hygiene. Daily oral pressure sprays aid healing by removal of impacted debris from necrotic tissue. Cultures often reveal oral candidiasis (thrush); the primary agent of choice is nystatin oral suspension (100,000 units/ml), which is taken orally as a 5-ml dose four times per day for 1 to
2 weeks. The nystatin is gargled for several minutes before swallowing. Ketoconazole is the preferred alternative and is taken orally as a 200-mg dose once a day for 1 to 2 weeks. All patients in this study were cultured and treated for candidiasis before the administration of the oral medications. Dyclone provided the best pain control, but was the least palatable. This solution is a ketone and a separate class of topical anesthetic. Dyclone effects surface anesthesia when applied to the mucous membrane. The mechanism of action is unknown. The next best solution was viscous lidocaine with 1% cocaine. Both solutions produced topical anesthesia and were allowed to coat the oral mucosa. No food or drink were taken for at least 15 minutes, in order for the medication to be effective; otherwise, the coating effect was washed
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
330
OtolaryngologyHead and Neck Surgery
CARNEL et al
Fig. 4. Photograph of pseudomembrane covering the field of radiation on the tongue.
away. The medications were swallowed or swished, depending upon the extent of the stomatitis. As previously indicated, swallowing may be difficult for some patients, but, if an explanation is given, aspiration is generally not a problem. This technique is used shortly before meals and helps maintain adequate nutrition. The anesthetic effect of the medications is not a contraindication for use at mealtime if used cautiously. Although not studied in this project, diet is mentioned for completeness. A semisolid-to-liquid diet is best tolerated. Baby foods, breakfast drinks, and vitamins are excellent supplements. Enteral hyperalimentation with commercially prepared products work extremely well if swallowing is temporarily interrupted. Diversions such as esophagectomy or gastrostomy are indicated for extensive oropharyngeal disease. Avoidance measures aid in the treatment of stomatitis. Alcohol, tobacco, or spicy foods intensify the reaction of the oral mucosa. Many commercial mouth lozenges and mouthwashes contain alcohol, which should be avoided. Aspirin causes acidification of the oral cavity and also may intensify the pain locally. Many medicated solutions have been recommended for the treatment of stomatitis, including dilute hydrogen peroxide (1 :3), five percent bicarbonate of soda, spray solution of pontocaine 0.5 percent, and viscous lidocaine. The list is long, allowing the physician or nurse a varied selection. As the intensity of pain increases, systemic oral analgesics are preferred over the
topical medications. This pilot study suggests guidelines for the use of three oral medications. The sample size is too small to draw definite conclusions. Further studies are indicated to better define the effectiveness of the many oral solutions available for the treatment of stomatitis induced by radiation therapy or chemotherapy or both. W e wish t o thank Troy H. Patience, BS, who acted as the statistician consultant, and Mrs. Pat Perez, who helped in the preparation of the manuscript. REFERENCES
1. Braham RL. Intra-oral problems associated with head and neck
2. 3.
4.
5. 6.
7.
8.
irradiation for malignant disease in children and adolescents. Practitioner 1981;225: 1309- 14. Adrian RM, Hood AF, Skarin A. Complications of chemotherapeutic agents. CA 1980;30;143-57. Schaaf JE. Dealing with oral complications in irradiated cancer patients. Alurni Bulletin IUND 1982;(Spring): 14-7. Artirn R, DiBella N, Bourg W. Relief of antineoplastic therapyinduced stomatitis pain with low concentration topical cocaine. Proceedings ASCO 1983;2:93. Weinstein GD. Methotrexate. Ann Intern Med 1977;86:199-204. Phillips TL, Fu KK. Quantification of combined radiation therapy and chemotherapy effects on critical normal tissue. Cancer 1976;37;1186- 1200. Coutard H. Roentgen therapy of epitheliomas of tonsillar regions, hypopharynx, and larynx, from 1920 to 1926. Am J Roentgenol 1932;28:313-31. Rubin P, Casarett GW. Clinical radiation pathology. 1st ed. Philadelphia: WB Saunders Co., 1968;121-51.
Downloaded from oto.sagepub.com at UNIV NEBRASKA LIBRARIES on June 5, 2016
