Prostate hypofractionated radiation therapy with injection of hyaluronic acid: acute toxicities in a phase 2 study.
OBJECTIVE
Hypofractionated radiation therapy (RT) in prostate cancer can be developed only if the risk of rectal toxicity is controlled. In a multicenter phase 2 trial, hypofractionated irradiation was combined with an injection of hyaluronic acid (HA) to preserve the rectal wall. Tolerance of the injection and acute toxicity rates are reported.


METHODS
The study was designed to assess late grade 2 toxicity rates. The results described here correspond to the secondary objectives. Acute toxicity was defined as occurring during RT or within 3 months after RT and graded according to the Common Terminology Criteria for Adverse Events version 4.0. HA tolerance was evaluated with a visual analog scale during the injection and 30 minutes after injection and then by use of the Common Terminology Criteria at each visit.


RESULTS
From 2010 to 2012, 36 patients with low-risk to intermediate-risk prostate cancer were included. The HA injection induced a mean pain score of 4.6/10 ± 2.3. Thirty minutes after the injection, 2 patients still reported pain (2/10 and 3/10), which persisted after the intervention. Thirty-three patients experienced at least 1 acute genitourinary toxicity and 20 patients at least 1 acute gastrointestinal toxicity. Grade 2 toxicities were reported for 19 patients with urinary obstruction, frequency, or both and for 1 patient with proctitis. No grade 3 or 4 toxicities were reported. At the 3-month visit, 4 patients described grade 2 obstruction or frequency, and no patients had any grade 2 gastrointestinal toxicities.


CONCLUSIONS
The injection of HA makes it possible to deliver hypofractionated irradiation over 4 weeks with a dose per fraction of > 3 Gy, with limited acute rectal toxicity.
Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France; EMR3738, Université Lyon 1, Lyon, France. Electronic address: olivier.chapet@chu-lyon.fr.
Olivier
O
Chapet
Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, France; Université Lyon 1, Lyon, France; EA SIS, Université de Lyon, Lyon, France.
Evelyne
E
Decullier
Pole Information Médicale Evaluation Recherche, Hospices Civils de Lyon, Lyon, France; Université Lyon 1, Lyon, France; EA SIS, Université de Lyon, Lyon, France.
Sylvie
S
Bin
Department of Urology, Clinique Beausoleil, Montpellier, France.
Antoine
A
Faix
Université Lyon 1, Lyon, France; Department of Urology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France.
Alain
A
Ruffion
Department of Medical Physics, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France.
Patrice
P
Jalade
Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier, France.
Pascal
P
Fenoglietto
Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France.
Corina
C
Udrescu
Department of Radiation Oncology, Hospices Civils de Lyon, Centre Hospitalier Lyon Sud, Pierre Benite, France.
Ciprian
C
Enachescu
Department of Radiation Oncology and Physics, Institut du Cancer de Montpellier, Montpellier, France.
David
D
Azria
D000230:Adenocarcinoma / Q000532:radiotherapy*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019583:Dose Fractionation, Radiation; D057918:Fiducial Markers; D041981:Gastrointestinal Tract / Q000528:radiation effects; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D007267:Injections / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D010147:Pain Measurement / Q000379:methods; D011467:Prostate / Q000473:pathology / Q000528:radiation effects*; D011471:Prostatic Neoplasms / Q000473:pathology / Q000532:radiotherapy*; D011832:Radiation Injuries / Q000517:prevention & control*; D061089:Radiotherapy, Image-Guided; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects / Q000379:methods*; D012007:Rectum / Q000528:radiation effects*; D014555:Urination Disorders / Q000209:etiology; D014566:Urogenital System / Q000528:radiation effects; D055675:Viscosupplements / Q000008:administration & dosage* / Q000009:adverse effects
D055675:Viscosupplements; D006820:Hyaluronic Acid