Prophylactic Use of Pentoxifylline and Tocopherol for Prevention of Osteoradionecrosis of the Jaw after Dental Extraction in Post-Radiated Oral and Oropharyngeal Cancer Patients: An Initial Case Series

Abstract

Osteoradionecrosis of the jaw is a morbid complication of radiotherapy in patients with oral and oropharyngeal cancers that may be precipitated by dental extractions. Pentoxifylline and tocopherol (PENTO) has been utilized in the management of osteoradionecrosis and as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. This observational study aims to report the outcome of the prophylactic use of PENTO in the prevention of osteoradionecrosis of the jaw after dental extractions in post-radiated oral and oropharyngeal cancer patients and to review the current literature on this topic. Four post-radiated oral and oropharyngeal oncology patients were referred to the dental oncology clinic of the University Dental Practice, University of Tennessee Health Sciences Center for dental extractions. All four patients were prescribed pentoxifylline 400 mg BID (twice a day) and tocopherol 400 IU BID (oral tablets) for 2 weeks before extraction(s) and for 6 weeks after extraction(s). All patients were followed up every week after the second week post-extraction if feasible until the extraction site(s) healed (covered by mucosa). The assessment endpoint was defined as 6 weeks post-extraction with the outcomes assessed as using four categories determined by the area of exposed bone: complete healing (complete mucosal coverage of extraction site); partial healing (reduction in size of extraction site); no change; and progression (increase in size of the extraction site). At the assessment endpoint, all patients had complete healing of all extraction sites. The ORN rate at the patient level (0/4) and individual tooth level (0/8) was 0%. All patients tolerated the PENTO medications and no adverse effects from the use of these medications were reported. This limited study in addition to the other reviewed studies estimates the rate of ORN at the patient level as 3.2% (14/436) for post-radiated head and neck oncology patients after dental extractions/invasive oral procedures. In conclusion, this PENTO regimen can reduce/prevent the incidence of ORN in post-radiated head and neck oncology patients. This safe and cost-effective protocol (PENTO regimen) should be further evaluated as prophylaxis for post-radiated head and neck oncology patients requiring an invasive dental procedure. We recommend large prospective studies to be carried out to further validate these findings.

Keywords: jaw; oral cancer; oropharyngeal cancer; osteoradionecrosis; pentoxifylline; radiation therapy; radiotherapy; vitamin E.

Figure 1

Post-radiated oral cancer survivor presenting to the dental oncology clinic with rampant dental caries.

Figure 2

A 57-year-old male oral cancer survivor was referred to the dental oncology clinic for the management of osteoradionecrosis. (A) Osteoradionecrosis of the left alveolar ridge with exposed bone. (B) Area of exposed bone covered with mucosa after being on pentoxifylline and tocopherol for 3 months.

Figure 3

A 69-year-old male patient managed with 70 Gy radiation therapy for his base of tongue squamous cell carcinoma (Case 1) was referred to the dental oncology clinic on account of a painful tooth (#19) associated with a draining abscess. Patient was prescribed antibiotics for a week prior to dental extraction for the draining abscess.

Figure 4

A 70-year-old male patient managed with 70 Gy radiation therapy for his right ventral tongue and floor of mouth squamous cell carcinoma (Case 2) was referred to the dental oncology clinic on account of painful teeth (#24, #25, #26, and #30) and oral rehabilitation.

Figure 5

A 69-year-old male patient managed with 70 Gy radiation therapy for his base of tongue squamous cell carcinoma (Case 1) placed on pentoxifylline and tocopherol before extraction of tooth #19. (A) Clinical picture of the post-extraction site at 3 weeks. (B) Clinical picture of the post-extraction site at 5 weeks showing complete mucosa coverage of the extraction site. (C) Clinical picture of the post-extraction site at 23 weeks.

Figure 6

A 70-year-old male patient managed with 70 Gy radiation therapy for his right ventral tongue and floor of mouth squamous cell carcinoma (Case 2) placed on pentoxifylline and tocopherol before extraction of teeth #24, #25, #26, #30. (A) Clinical picture of post-extraction sites at 2 weeks. (B) Clinical picture of post-extraction sites at 5 weeks showing complete mucosa coverage of the extraction site. (C) Clinical picture of the post-extraction site at 7 weeks.

Figure 7

A 59-year-old female patient managed with 70 Gy radiation therapy for her right tonsil squamous cell carcinoma (Case 3) placed on pentoxifylline and tocopherol before extraction of tooth #19. A clinical picture of the post-extraction site at 4 weeks showing complete mucosa coverage of the extraction site.