The Impact of Pentoxifylline and Vitamin E on Radiotherapy-induced Toxicity in Head & Neck Cancer Patients

The Impact of Pentoxifylline and Vitamin E on The Incidence and Severity of Radiotherapy- Induced Oral Mucositis and Dysphagia in Patients With Head and Neck Cancer

The purpose of this study is to determine whether pentoxifylline and vitamin E are effective in prevention of radiotherapy- induced toxicity in head and neck cancer patients treated with concurrent chemoradiotherapy.

Study Overview

• Status: Completed
• Conditions: Head and Neck Neoplasms
• Intervention / Treatment: Drug: Cisplatin; Radiation: Radiation therapy; Drug: Vitamin E; Drug: Pentoxifylline

Detailed Description

This is a randomized controlled prospective study of pentoxifylline and vitamin E given on daily basis throughout the period of concurrent chemoradiotherapy to patients with carcinoma of the head and neck. All patients will be followed up to 90 days since the first day of treatment. The incidence and severity of adverse events will be assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2

Contacts and Locations

Study Locations

• Egypt
  • Cairo, Egypt
    • Ain Shams University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult patients
• Measurable disease
• Patients with squamous cell carcinoma of the head and neck eligible for treatment with concurrent chemo- radiotherapy
• Able to understand and willing to sign a written informed consent document

Exclusion Criteria:

• Pregnant or lactating women, since imaging cannot be done in this setting.
• Patients treated with vitamin E and/ or pentoxifylline for any other indication
• Patients with recent cerebral and/or retinal hemorrhage
• Patients who have previously exhibited intolerance to pentoxifylline or methylxanthines such as caffeine, theophylline, and theobromine.
• Patients treated with oral anticoagulants.
• Absolute neutrophil count ≤1.5×109/L
• Platelets ≤100×109/L
• AST ≥ 2.5 X institutional upper limit normal (ULN)
• Serum creatinine ≥ 1.5 mg% for males & 1.4 mg% for females
• Serum bilirubin ≥ 1.5X institutional upper limit normal (ULN)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Platinum based concurrent chemoradiotherapy [cisplatin (100mg/m2) on day 1, 22 and 43 of Radiotherapy (at 2 Gy/ fraction to a dose of 70 Gy over 7 weeks] . Pentoxifylline 400 mg oral tablets twice daily for 7 weeks. Vitamin E 1000 mg oral capsules once daily for 7 weeks.	Drug: Cisplatin; Radiation: Radiation therapy; Drug: Vitamin E; Drug: Pentoxifylline; Other Names: Trental
Active Comparator: Control Group; Platinum based concurrent chemoradiotherapy [cisplatin (100mg/m2) on day 1, 22 and 43 of Radiotherapy (at 2 Gy/ fraction to a dose of 70 Gy over 7 weeks] .	Drug: Cisplatin; Radiation: Radiation therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of radiotherapy-induced toxicity	weekly follow-up for recording radiotherapy-induced toxicity occurrence.weekly reported toxicities will be graded according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03	90 days since start of treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of grade 3 or 4 radiotherapy-induced toxicity		90 days since start of treatment
Patients' response to concurrent chemo-radiotherapy (objective response rate)	the effect of pentoxifylline and vitamin E on the	63 days since start of treatment
incidence and grade of pentoxifylline and vitamin E- related adverse events (National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03)	Adverse events induced by intervention drugs will be assessed according to National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03	90 days since start of treatment
Number of patients with unplanned breaks in radiotherapy		49 days since start of treatment
Total dose of opioid analgesics required		90 days since start of treatment
Functional oral intake score		90 days since start of treatment
Patients' quality of life assessed using the validated Arabic version of the EuroQol-5D-3L questionnaire		90 days since start of treatment

Collaborators and Investigators

• Sponsor: Ain Shams University

Publications and helpful links

General Publications

• Sayed R, El Wakeel L, Saad AS, Kelany M, El-Hamamsy M. Pentoxifylline and vitamin E reduce the severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients: a randomized, controlled study. Med Oncol. 2019 Nov 21;37(1):8. doi: 10.1007/s12032-019-1334-5.

Study record dates

Study Major Dates

• Study Start (Actual): May 2, 2015
• Primary Completion (Actual): June 30, 2018
• Study Completion (Actual): June 30, 2018

Study Registration Dates

• First Submitted: March 16, 2015
• First Submitted That Met QC Criteria: March 19, 2015
• First Posted (Estimate): March 25, 2015

Study Record Updates

• Last Update Posted (Actual): November 26, 2019
• Last Update Submitted That Met QC Criteria: November 23, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Head and Neck Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Micronutrients; Vitamins; Antioxidants; Phosphodiesterase Inhibitors; Free Radical Scavengers; Radiation-Protective Agents; Vitamin E; Pentoxifylline
• Other Study ID Numbers: Ph.D 20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED