title: Radiotherapy and concurrent metronomic chemotherapy in hormone-refractory prostate carcinoma: a Phase I study.
abstract: OBJECTIVE
  To determine the maximum tolerated dose of hypofractionated radiotherapy (HFRT) plus concurrent metronomic chemotherapy in patients with hormone-refractory prostate cancer (HRPC).
  
  
  METHODS
  A Phase I clinical trial was performed with cohorts of three to six patients per group. Eligible patients had HRPC without distant metastases. The radiotherapy dose was escalated in a stepwise fashion as follows: 60, 65, and 70 Gy at levels 1, 2, and 3, respectively (25 fractions: levels 1-2, and 26 fractions: level 3).
  
  
  RESULTS
  Nine patients were enrolled. The radiotherapy dose was escalated from 60 to 70 Gy without any dose-limiting toxicity. The most common grade 1/2 toxicities were hematuria, dysuria, diarrhea and rectal-perirectal pain. The overall objective response rate was 9/9 (100%) (95% CI=66.4%-100%). The median time-to-progression was 19 months.
  
  
  CONCLUSIONS
  In the challenging setting of HRPC, HFRT up to 70 Gy with concurrent metronomic chemotherapy was well-tolerated and yielded encouraging disease control.
authors.affiliation: Department of Radiotherapy, Research and Care Foundation "Giovanni Paolo II", Catholic University of Sacred Heart, Largo A. Gemelli 1, 86100 Campobasso, Italy. gmacchia@rm.unicatt.it.
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Morganti
authors.forename: Mariangela
authors.initials: M
authors.lastname: Massaccesi
authors.forename: Luciana
authors.initials: L
authors.lastname: Caravatta
authors.forename: Gabriella
authors.initials: G
authors.lastname: Macchia
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Picardi
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.forename: Edy
authors.initials: E
authors.lastname: Ippolito
authors.forename: Samantha
authors.initials: S
authors.lastname: Mignogna
authors.forename: Marica
authors.initials: M
authors.lastname: Ferro
authors.forename: Savino
authors.initials: S
authors.lastname: Cilla
authors.forename: Gian Carlo
authors.initials: GC
authors.lastname: Mattiucci
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000628:therapy*; D059250:Administration, Metronomic; D000368:Aged; D000369:Aged, 80 and over; D059248:Chemoradiotherapy; D018572:Disease-Free Survival; D019583:Dose Fractionation, Radiation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011446:Prospective Studies; D064129:Prostatic Neoplasms, Castration-Resistant / Q000401:mortality / Q000628:therapy*; D016896:Treatment Outcome
keywords: Chemoradiation; hormone-refractory prostate cancer; metronomic chemotherapy; phase I study