Complete restoration of refractory mandibular osteoradionecrosis by prolonged treatment with a pentoxifylline-tocopherol-clodronate combination (PENTOCLO): a phase II trial.

Abstract

PURPOSE:

Osteoradionecrosis (ORN) is a nonhealing wound of the bone that is difficult to manage. Combined treatment with pentoxifylline and vitamin E reduces radiation-induced fibrosis and ORN with a good prognosis. We previously showed that the combination of pentoxifylline and vitamin E with clodronate (PENTOCLO) is useful in healing sternocostal and some mandibular ORN. Is PENTOCLO effective in ORN of poor prognosis?

METHODS:

54 eligible patients previously irradiated for head and neck cancer (among 72 treated) a mean 5 years previously received exteriorized refractory mandibular ORN for 1.4 ± 1.8 years, mainly after local surgery and hyperbaric oxygen had been ineffective. The mean length of exposed bone (D) was 17 ± 8 mm as primary endpoint, and the mean Subjective, Objective, Management, and Analytic evaluation of injury (SOMA) score was 16 ± 4. Between August 2000 and August 2008, all patients were given daily oral PENTOCLO: 800 mg pentoxifylline, 1,000 IU vitamin E, and 1,600 mg clodronate 5 days per week alternating with 20 mg prednisone and 1,000 mg ciprofloxacin 2 days per week. The duration of treatment was related to consolidated healing.

RESULTS:

Prolonged treatment (16 ± 9 months) was safe and well tolerated. All patients improved, with an exponential progressive--(f[t] = a.exp(-b.t)--and significant (p < 0.0001) reduction of exposed bone (D), respectively (months): D(2) -42%, D(4) -62%, D(6) -77%, D(12) -92%, and D(18) -96%, combined with iterative spontaneous sequestrectomies in 36 patients. All patients experienced complete recovery in a median of 9 months. Clinical improvement was measured in terms of discontinuation of analgesics, new fracture, closed skin fistulae, and delayed radiologic improvement: SOMA(6) -64%, SOMA(12) -89%, and SOMA(30) -96%.

CONCLUSION:

Long-term PENTOCLO treatment is effective, safe, and curative for refractory ORN and induces mucosal and bone healing with significant symptom improvement. These findings will need to be confirmed in a randomized trial.

• Authors: Sylvie Delanian, Cécile Chatel, Raphael Porcher, Joel Depondt, Jean-Louis Lefaix
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 80 Issue 3 Pg. 832-9 (Jul 01 2011) ISSN: 1879-355X [Electronic] United States
• PMID: 20638190 (Publication Type: Clinical Trial, Phase II, Journal Article)
• Copyright: Copyright © 2011 Elsevier Inc. All rights reserved.

Chemical References

• Bone Density Conservation Agents
• Drug Combinations
• pentoxifylline-tocopherol-clodronate
• Clodronic Acid
• Ciprofloxacin
• Tocopherols
• Pentoxifylline
• Prednisone

Topics

• Adult
• Aged
• Aged, 80 and over
• Bone Density Conservation Agents (therapeutic use)
• Ciprofloxacin (therapeutic use)
• Clodronic Acid (therapeutic use)
• Drug Administration Schedule
• Drug Combinations
• Female
• Head and Neck Neoplasms (radiotherapy)
• Humans
• Male
• Mandibular Diseases (drug therapy)
• Middle Aged
• Osteoradionecrosis (drug therapy)
• Pentoxifylline (therapeutic use)
• Prednisone (therapeutic use)
• Prognosis
• Tocopherols (therapeutic use)