Trial of Pentoxifylline in Patients With Functional Disability Caused by Radiation-Induced Advanced Regional Fibrosis
Trial of Pentoxifylline in Patients With Functional Disability Caused by Radiation-Induced Advanced Regional Fibrosis
After initial assessment of their condition by specified clinical and laboratory parameters,
 each of the patients will be treated for 8 weeks at the standard pentoxifylline dose (400 mg
 po TID). Objective and subjective response parameters will be re-assessed at the end of the
 treatment and 8 weeks later for possible decay of response.
Patients with late fibrovascular sequelae of radiation or of combined radiation and surgery,
 with quantifiable symptomatology or disability, will be eligible for this trial. This
 protocol is designed as an open label one arm study. (A placebo controlled randomized trial
 was approved by the IRB but after extensive negotiation, drug and placebo in slow release
 formulation will not be provided by the manufacturer). Up to fifty patients will be
 recruited. After initial assessment of their condition by specified clinical and laboratory
 parameters, each of the patients will be treated for 8 weeks at the standard pentoxifylline
 dose (400 mg po TID). Objective and subjective response parameters will be re-assessed at the
 end of the treatment and 8 weeks later for possible decay of response.

 In addition to symptomatic objective and subjective response, blood and urine will be
 collected for TNF, TGF-beta, and FGF. Cutaneous blood flow and collagen subtyping will be
 performed on a subset of patients using Laser Doppler, functional MRI techniques and
 subcutaneous tissue biopsies. We will examine for correlation between clinical response and
 these biological responses.
POPULATION CHARACTERISTICS:

 Regional advanced postradiation fibrosis of the neck, chest wall, pelvis, or extremities
 causing measurable impairment of specific function, i.e.: Decreased range of motion,
 Weakness, Sensory deficit, Pain requiring narcotics, Significantly altered activities of
 daily living.

 None of these conditions present either before or during radiotherapy or attributed to
 surgery or chemotherapy.

 Patients with prostate cancer allowed if prostate-specific antigen (PSA) is less than 4.0
 ng/mL and the last 3 PSA values were stable or decreasing. Abnormal bone scan or film
 acceptable if consistent with degenerative disease.

 No recurrent or metastatic cancer.

 No concurrent second cancer.

 PRIOR/CONCURRENT THERAPY: At least 3 months since pentoxifylline.

 PATIENT CHARACTERISTICS:

 Age: 18 and over.

 Performance status: Karnofsky 70%-100% (unrelated to postradiation fibrosis).

 CARDIOVASCULAR:

 No symptomatic coronary artery disease with frequent anginal episodes necessitating any of
 the following during past 6 months: Coronary artery bypass, Angioplasty, Pacemaker
 placement, Thrombolytic treatment.

 No chronic cardiac failure with persistent hemodynamic abnormality and ejection fraction
 less than 40%.

 No coagulation, platelet, or vascular disorder that threatens to cause bleeding.

 OTHER:

 No intolerance to pentoxifylline or other xanthines (e.g., caffeine, theophylline,
 theobromine).

 No seizure disorder.

 No peptic ulcer disease.

 Willing to undergo serial evaluations (excluding biopsies, laser Doppler, MRI) by NCI
 rehabilitation specialist for documentation and grading of functional disability.

 No pregnant or nursing women.

 Adequate contraception encouraged in fertile women.