Gothard L, Cornes P, Earl J, Hall E, MacLaren J, Mortimer P, Peacock J, Peckitt C, Woods M, Yarnold J, et al.
Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncol.... Date of publication 2004 Nov 1;volume 73(2):133-9.
1. Radiother Oncol. 2004 Nov;73(2):133-9.
Double-blind placebo-controlled randomised trial of vitamin E and pentoxifylline
in patients with chronic arm lymphoedema and fibrosis after surgery and
radiotherapy for breast cancer.
Gothard L(1), Cornes P, Earl J, Hall E, MacLaren J, Mortimer P, Peacock J,
Peckitt C, Woods M, Yarnold J.
Author information:
(1)Department of Radiotherapy, Royal Marsden Hospital, Sutton, Surrey, UK.
BACKGROUND AND PURPOSE: Treatment-induced arm lymphoedema is a common and
distressing complication of curative surgery and radiotherapy for early breast
cancer. A number of studies testing alpha-tocopherol (vitamin E) and
pentoxifylline suggest evidence of clinical regression of superficial
radiation-induced fibrosis but there is only very limited evidence from
randomised trials. Arm lymphoedema after lymphatic radiotherapy and surgery has
been used in the present study as a clinical system for testing these drugs in a
double-blind placebo-controlled randomised phase II trial.
PATIENTS AND METHODS: Sixty-eight eligible research volunteers with a minimum 20%
increase in arm volume at a median 15.5 years (range 2-41) after
axillary/supraclavicular radiotherapy (plus axillary surgery in 51/68 (75%)
cases) were randomised to active drugs or placebo. All volunteers were given
dl-alpha tocopheryl acetate 500 mg twice a day orally plus pentoxifylline 400 mg
twice a day orally, or corresponding placebos, for 6 months. The primary endpoint
was volume of the ipsilateral limb measured opto-electronically using a perometer
and expressed as a percentage of the contralateral limb volume.
RESULTS: At 12 months post-randomisation, there was no significant difference
between treatment and control groups in terms of arm volume. Absolute change in
arm volume at 12 months was 2.5% (95% CI -0.40 to 5.3) in the treatment group
compared to 1.2% (95% CI -2.8 to 5.1) in the placebo group. The difference in
mean volume change between randomisation groups at 12 months was not
statistically significant (P = 0.6), -1.3% (95% CI -6.1 to 3.5), nor was there a
significant difference in response at 6 months (P = 0.7), where mean change in
arm volume from baseline in the treatment and placebo groups was -2.3% (95% CI
-7.9 to 3.4) and -1.1% (95% CI -3.9 to 1.7), respectively. There were no
significant differences between randomised groups in terms of secondary
endpoints, including tissue induration (fibrosis) in the irradiated breast or
chest wall, pectoral fold or supraclavicular fossa, change in photographic
breast/chest wall appearance or patient self-assessment of function and Quality
of Life at either 6 or 12 months.
CONCLUSIONS: The study fails to demonstrate efficacy of dl-alpha tocopheryl
acetate plus pentoxifylline in patients with arm lymphoedema following axillary
surgery and lymphatic radiotherapy, nor does it suggest any benefits of these
drugs in radiation-induced induration (fibrosis) in the breast, chest wall,
pectoral fold, axilla or supraclavicular fossa.
DOI: 10.1016/j.radonc.2004.09.013
PMID: 15542159 [Indexed for MEDLINE]
