Phase III study of ibuprofen versus placebo for radiation-induced genitourinary side effects.
OBJECTIVE
On the basis of our anecdotal clinical observations that nonsteroidal anti-inflammatory agents relieved dysuria during radiotherapy for patients with prostate cancer, we conducted a Phase III randomized trial of ibuprofen vs. placebo for patients who had an increase in acute urinary symptoms. Our in vitro and in vivo laboratory data with a higher concentration of ibuprofen than achievable in this study demonstrated radiosensitization. This study examined whether the inflammatory response within the prostate during radiotherapy would respond to the standard dose of ibuprofen as assessed by a symptom score.


METHODS
Patients were registered to the study and were followed weekly with a formal symptom assessment. A double-blind randomization to ibuprofen, 400 mg q.i.d., vs. placebo for 7 days was done at a time when the severity score increased. The symptom response was evaluated at the end of the week.


RESULTS
Between 1995 and 1998, 100 patients were entered, 28 did not have a sufficient change in symptom score to be randomized, and 19 were either unable to take ibuprofen or withdrew before randomization. Of the 53 patients randomized, 27 received placebo and 26 ibuprofen. No statistically significant differences were found between the placebo and ibuprofen groups between baseline and randomization or between randomization and the 1-week posttreatment assessment. Neither group had a change in symptom severity between randomization and the 1-week posttreatment evaluation.


CONCLUSIONS
The standard anti-inflammatory dose of ibuprofen did not relieve the acute urinary or rectal symptoms during radiotherapy for prostate cancer. The nonsteroidal anti-inflammatory drugs are potential radiation sensitizers with the mechanism of action as yet unknown. Clinical trials of the cyclooxygenase inhibitors as radiation sensitizers should explore a range of doses and evaluate potential mechanisms of action, including cyclooxygenase inhibition and other non-cyclooxygenase mechanisms.
Coleman
C Norman
CN
Joint Center for Radiation Therapy, Harvard Medical School, Boston, MA, USA. ccoleman@mail.nih.gov
Kelly
Laura
L
Riese Daly
Nancy
N
Beard
Clair
C
Kaplan
Irving
I
Lamb
Carolyn
C
Propert
Kathleen
K
Manola
Judith
J
D000368:Aged; D000369:Aged, 80 and over; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use*; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D004311:Double-Blind Method; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000528:radiation effects*; D011471:Prostatic Neoplasms / Q000532:radiotherapy*; D011878:Radiotherapy / Q000009:adverse effects*; D014570:Urologic Diseases / Q000188:drug therapy* / Q000209:etiology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D007052:Ibuprofen