Randomized, Placebo-Controlled Clinical Trial Combining Pentoxifylline-Tocopherol and Clodronate in the Treatment of Radiation-Induced Plexopathy.

Abstract

PURPOSE:

Radiation-induced (RI) plexopathy is a rare peripheral nerve injury after radiation therapy for cancer. No treatment has been shown to slow its progression. A pentoxifylline-vitamin E combination significantly reduced RI fibrosis, and its association with clodronate (PENTOCLO) allowed healing of osteoradionecrosis and reduction of neurologic symptoms in phase 2 trials.

METHODS AND MATERIALS:

A placebo-controlled, double-blind trial conducted in adults with RI limb plexopathy without cancer recurrence, randomized in 2 arms to PENTOCLO (pentoxifylline 800 mg, tocopherol 1000 mg, clodronate 1600 mg 5 days per week) or triple placebo. The primary outcome measure after 18 months of treatment was the neurologic Subjective Objective Management Analytic (SOMA) score evaluating pain, paresthesia, and motor disability.

RESULTS:

Between 2011 and 2015, 59 patients were included: 1 false inclusion (neoplastic plexopathy), 29 treated with placebo (group P), and 29 treated with the active drugs (group A); 46 patients presented an upper-limb and 12 a lower-limb plexopathy. The mean delay after irradiation was 26 ± 8 years, for patients with neurologic symptoms for 5 ± 5 years. The median global SOMA scores in the P and A groups, respectively, were 9 (range, 6-11) versus 9 (range, 8-11) at M0 and 9 (range, 5-12) versus 10 (range, 6-11) at M18 without any significant difference. Analysis of the secondary outcomes showed that SOMA score subdomains for pain and paresthesia were more affected in group A (not significant). The frequency of adverse events was similar in the 2 groups (81% of patients): slight expected vascular-gastrointestinal symptoms in A, but a large excess of RI complications (arterial stenosis).

CONCLUSIONS:

This first randomized drug trial in RI plexopathy failed to show a beneficial effect. More studies are needed in patients with less advanced disease and fewer confounding comorbidities and with a more sensitive measure to detect a therapeutic effect.

• Authors: Sylvie E Delanian, Timothee Lenglet, Thierry Maisonobe, Matthieu Resche-Rigon, Pierre-Francois Pradat
• Journal: International journal of radiation oncology, biology, physics (Int J Radiat Oncol Biol Phys) Vol. 107 Issue 1 Pg. 154-162 (05 01 2020) ISSN: 1879-355X [Electronic] United States
• PMID: 31987975 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• Drug Combinations
• Placebos
• pentoxifylline-tocopherol-clodronate
• Clodronic Acid
• Tocopherols
• Pentoxifylline

Topics

• Aged
• Clodronic Acid (therapeutic use)
• Drug Combinations
• Female
• Humans
• Male
• Middle Aged
• Pentoxifylline (therapeutic use)
• Peripheral Nerve Injuries (drug therapy, etiology)
• Placebos
• Radiation Injuries (drug therapy)
• Tocopherols (therapeutic use)
• Treatment Outcome