Phase II trial of radiation dose escalation with conformal external beam radiotherapy and high-dose-rate brachytherapy combined with long-term androgen suppression in unfavorable prostate cancer: feasibility report.
OBJECTIVE
To determine the feasibility of combined long-term luteinizing hormone-releasing hormone agonist-based androgen suppressive therapy (AST) and dose escalation with high-dose-rate (HDR) brachytherapy for high-risk (HRPC) or very-high-risk prostate cancer (VHRPC).


METHODS
Between January 2001 and October 2006, 134 patients (median age, 70 years) with either National Comprehensive Cancer Network criteria-defined HRPC (n = 47, 35.1%) or VHRPC (n = 87, 64.9%) were prospectively enrolled in this Phase II trial. Tumor characteristics included a median pretreatment prostate-specific antigen level of 14.6 ng/mL, a median clinical stage of T2c, and a median Gleason score of 7. Three-dimensional conformal radiotherapy (54 Gy in 30 fractions) was followed by HDR brachytherapy (19 Gy in 4 b.i.d. treatments). Androgen suppressive therapy started 0-3 months before three-dimensional conformal radiotherapy and continued for 2 years.


RESULTS
One implant was repositioned with a new procedure (0.7%). Five patients (3.7%) discontinued AST at a median of 13 months (range, 6-18 months) because of disease progression (n = 1), hot flashes (n = 2), fatigue (n = 1), and impotence (n = 1). After a median follow-up of 37.4 months (range, 24-90 months), the highest Radiation Therapy Oncology Group-defined late urinary toxicities were Grade 0 in 47.8%, Grade 1 in 38.1%, Grade 2 in 7.5%, and Grade 3 in 6.7% of patients. Maximal late gastrointestinal toxicities were Grade 0 in 73.1%, Grade 1 in 16.4%, Grade 2 in 7.5%, and Grade 3 in 2.9% of patients. There were no Grade 4 or 5 events.


CONCLUSIONS
Intermediate-term results show that dose escalation with HDR brachytherapy combined with long-term AST is feasible and has a toxicity profile similar to that reported by previous HDR brachytherapy studies.
Department of Oncology, Clínica Universitaria de Navarra, University of Navarre, Navarre, Spain.
Jeanette
J
Valero
Mauricio
M
Cambeiro
Carlos
C
Galán
Mercedes
M
Teijeira
Pilar
P
Romero
Javier
J
Zudaire
Marta
M
Moreno
Raquel
R
Ciérvide
José Javier
JJ
Aristu
Rafael
R
Martínez-Monge
D000368:Aged; D000369:Aged, 80 and over; D000726:Androgen Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D003131:Combined Modality Therapy / Q000009:adverse effects / Q000379:methods; D019583:Dose Fractionation, Radiation; D005240:Feasibility Studies; D041981:Gastrointestinal Tract / Q000528:radiation effects; D007987:Gonadotropin-Releasing Hormone / Q000819:agonists; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D014566:Urogenital System / Q000528:radiation effects
D000726:Androgen Antagonists; D007987:Gonadotropin-Releasing Hormone; D017430:Prostate-Specific Antigen