Clinical Investigation
Randomized Trial of Pentoxifylline and Vitamin E vs Standard Follow-up After Breast Irradiation to Prevent Breast Fibrosis, Evaluated by Tissue Compliance Meter

Presented in abstract form at the 94th Annual Meeting of the American Radium Society, April 28-May 2, 2012, Las Vegas, NV.
https://doi.org/10.1016/j.ijrobp.2012.06.042Get rights and content

Purpose

To conduct a randomized clinical trial to determine whether the combination of pentoxifylline (PTX) and vitamin E given for 6 months after breast/chest wall irradiation effectively prevents radiation-induced fibrosis (RIF).

Methods and Materials

Fifty-three breast cancer patients with localized disease were enrolled and randomized to treatment with oral PTX 400 mg 3 times daily and oral vitamin E 400 IU daily for 6 months after radiation (n=26), or standard follow up (n=27). Tissue compliance meter (TCM) measurements were obtained at 18 months to compare tissue compliance in the irradiated and untreated breast/chest wall in treated subjects and controls. Measurements were obtained at 2 mirror image sites on each breast/chest wall, and the average difference in tissue compliance was scored. Differences in TCM measurements were compared using a t test. Subjects were followed a minimum of 2 years for local recurrence, disease-free survival, and overall survival.

Results

The mean difference in TCM measurements in the 2 groups was 0.88 mm, median of 1.00 mm (treated) and 2.10 mm, median of 2.4 mm (untreated). The difference between the 2 groups was significant (P=.0478). Overall survival (100% treated, 90.6% controls at 5 years) and disease-free survival (96.2% treated, 86.8% controls at 5 years) were not significantly different in the 2 groups.

Conclusions

This study of postirradiation breast cancer patients treated with PTX/vitamin E or standard follow-up indicated a significant difference in radiation-induced fibrosis as measured by TCM. There was no observed impact on local control or survival within the first 2 years of follow-up. The treatment was safe and well tolerated. Pentoxifylline/vitamin E may be clinically useful in preventing fibrosis after radiation in high-risk patients.

Introduction

Excluding skin cancer, breast cancer is the most common cancer in American women. It is estimated that in 2011 more than 230,000 invasive breast cancers and more than 57,000 noninvasive breast cancers will be diagnosed in the United States (1). Women with early breast cancer may be treated with breast conservation, which usually includes limited surgery followed by breast irradiation. Women treated with mastectomy may have indications for postoperative radiation based on tumor size, lymph node involvement, or other adverse factors. The death rate in the United States from breast cancer has been decreasing since 1990, and there are more than 2.6 million breast cancer survivors. Because many patients will live for decades after completing treatment, minimizing side effects of treatment and maintaining quality of life are extremely important.

Radiation-induced fibrosis (RIF) is a common side effect of therapeutic irradiation that can result in pain, poor cosmesis, and functional impairment. Previously, RIF was considered irreversible. Pentoxifylline (PTX) combined with vitamin E has been demonstrated in both preclinical and clinical studies to reverse chronic RIF. Delanian et al (2) performed a placebo-controlled trial of combined PTX and tocopherol in women who had clinically measurable RIF after radiation therapy for breast cancer and demonstrated reversal of RIF in the treated group. This work supported the concept of RIF as a modifiable, and possibly preventable, process. We conducted an institutional randomized clinical trial to determine whether PTX and vitamin E, both given orally for 6 months after completion of breast or chest wall irradiation, was effective in preventing regional RIF. Clinical assessment of fibrosis is qualitative and subjective. We selected the tissue compliance meter (TCM) as a quantitative assessment of tissue compliance to measure fibrosis. The TCM is a hand-held device that was developed for physical therapy assessment and validated for quantitative assessment of tissue compliance in breast tissue (3). We measured postradiation therapy tissue compliance in the treated and untreated breast/chest wall with a TCM (4).

Section snippets

Methods and Materials

This prospective, randomized study was approved by our institutional review board IRB-01 (biomedical). Eligible subjects were patients with breast cancer treated with breast conservation or after mastectomy, without metastatic disease. Informed consent was obtained before study entry. The trial utilized a block randomization with a block size of 4 and 6 and an allocation ratio of 1:1 (control: study intervention). The study used convenience sampling; all eligible patients were approached

Results

The majority of patients (47 of 53) were treated with breast conservation: lumpectomy and sentinel node sampling or axillary lymph node dissection, followed by radiation to the whole breast.

Six patients were treated after mastectomy (Table 1). No attempt was made to stratify patients according to hormone or chemotherapy treatment. However, the differences between these treatment factors in the 2 groups were not significant: 9 of 26 study patients and 13 of 27 control patients had chemotherapy

Discussion

Radiation-induced fibrosis is a chronic late effect of therapeutic radiation that, until the 1990s, was considered irreversible. Preclinical work at this institution demonstrated that PTX reduced the incidence and severity of late radiation injury in the mouse extremity (8). Lefaix et al (9) demonstrated that PTX and vitamin E enhanced healing of full-thickness skin grafts in irradiated pigskin. A clinical pilot study at this institution indicated that PTX was effective in healing soft-tissue

References (17)

There are more references available in the full text version of this article.

Cited by (79)

  • Advances in Radiotherapy for Brain Metastases

    2023, Surgical Oncology Clinics of North America
  • Evidence-Based Guidance for Breast Cancer Survivorship

    2023, Hematology/Oncology Clinics of North America
  • Late toxicities management

    2023, Palliative Radiation Oncology
  • Interventions for Radiation-Induced Fibrosis in Patients With Breast Cancer: Systematic Review and Meta-analyses

    2022, Advances in Radiation Oncology
    Citation Excerpt :

    We excluded 2094 after title and abstract analysis and 7 after reading the full text. Nine publications (7 studies) were included: Bourgeois et al,7 Brooker et al19 and their protocol NCT00041223,30 Delanian et al,12 Gothard et al,14 Jacobson et al16 and their protocol NCT00583700,31 Magnusson et al15 and Oliveira et al.8 The main characteristics of the 7 included studies are presented in Table 1. After judging the risk of bias, we observed methodological limitations with high risk of bias in 18% of the domains.

View all citing articles on Scopus

Conflict of interest: none.

View full text