Effect of Edaravone on Radiation-induced Temporal Lobe Necrosis

Sun Yat-sen University

Status and phase: Completed; Phase 2

Conditions: Nasopharyngeal Carcinoma; Brain Necrosis

Treatments: Drug: Edaravone; Other: Common fundamental management

Study type: Interventional

Funder types: Other

Identifiers

NCT01865201

2009001

Details and patient eligibility

About

It is hypothesized that excessive generation of free radicals involves in the pathogenesis of radiation-induced brain necrosis. This study therefore evaluated the effect of free radical scavenger, edaravone, on radiation-induced temporal lobe necrosis (TLN) in patients with nasopharyngeal carcinoma (NPC) after radiotherapy.

Full description

Radiation-induced temporal lobe necrosis (TLN) is the most serious sequelae of radiotherapy and impairs the patients' quality of life profoundly. Steroid is one of the conventional treatment methods for TLN. However, its response rate was still not so satisfactory (about 30%-35%).The mechanism of TLN is under exploring and not completely understood. It has been proposed recently that chronic oxidative stress and inflammation involve in the pathogenesis of radiation-induced late normal tissue injury.

Edaravone(3-methyl-1-phenyl-2-pyrazolin-5-one), which is proved to be an excellent free radical scavenger, has been applied to a wide range of oxidative stress-related diseases.Thus, it may exert a therapeutic effect on radiation-induced temporal lobe necrosis. To support this hypothesis, the investigators carried out a randomized study of combining edaravone with common fundamental management versus common fundamental therapy in patients with TLN, and analyzed the Late Effects of Normal Tissues -Subjective, Objective, Management, Analytic (LENT/SOMA) scale before and after treatment.

Enrollment: 154 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• ①Patients must have received radiation therapy for histologically confirmed nasopharyngeal carcinoma.

  • Prior irradiation >/= 6 months prior to study entry.

    • Radiographic evidence to support the diagnosis of radiation-induced temporal lobe necrosis without tumor recurrence(15).

      • Age>/= 18 years.

        • No evidence of very high intracranial pressure that suggests brain hernia and need surgery.

          • Fertile women who are willing to take contraception during the trial.

            • Routine laboratory studies with bilirubin </=2 * upper limits of normal (ULN), aspartate aminotransferase (AST or SGOT) < 2 * ULN, creatinine <1.5 * ULN, red-cell count >/= 4,000 per cubic millimeter; white-cell count >/=1500 per cubic millimeter, platelets >/= 75,000 per cubic millimeter; Hb >/=9.0. prothrombin time(PT), activated partial thromboplastin time(APTT),international normalized ratio(INR) in a normal range.

              • Ability to understand and willingness to sign a written informed consent document.

Exclusion criteria

• ①Tumor recurrence or metastases.

  • Diseases of central nervous system, such as cerebral vascular events, inflammatory, degenerative disease, and significant cardiovascular diseases.

    • Severe systemic diseases.

      • History of anaphylactic response to edaravone.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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154 participants in 2 patient groups

Edaravone group

Experimental group

Description:

Edaravone was used at a dose of 30mg,intravenously, twice per day, for 14 days. All patients also received common fundamental management, which was as follows: ①Methylprednisolone, administered by intravenous infusion at a 500mg daily for 3 consecutive days and then gradually tailed off in 30 days with administration of oral prednisolone. ②Dehydration drugs.

Treatment:

Drug: Edaravone

Control group

Experimental group

Description:

All patients in this group received common fundamental management, which was as follows: ①Methylprednisolone, administered by intravenous infusion at a 500mg daily for 3 consecutive days and then gradually tailed off in 30 days with administration of oral prednisolone. ②Dehydration drugs.

Treatment:

Other: Common fundamental management