title: Neoadjuvant accelerated concomitant boost radiotherapy and multidrug chemotherapy in locally advanced rectal cancer: a dose-escalation study.
abstract: OBJECTIVE
  To determine the maximal and safely dose of preoperative radiotherapy and concurrently intensified chemotherapy regimen (raltitrexed plus oxaliplatin) in locally advanced rectal cancer patients.
  
  
  METHODS
  Patients with cT3-T4 and/or cN≥1 or locally recurrent rectal cancer were sequentially assigned to 4 treatment schedules of chemoradiation: standard radiotherapy (50.4 Gy/5.5 wk) plus raltitrexed (cohort A), accelerated radiotherapy (55 Gy/5 wk) plus raltitrexed (cohort B), standard radiotherapy plus raltitrexed and oxaliplatin (cohort C), accelerated radiotherapy plus raltitrexed and oxaliplatin (cohort D). Patients were treated in cohorts of 6 to 12 per group. The maximal tolerated dose was exceeded if more than one-third of patients in a given cohort experienced dose-limiting toxicity (DLT). DLT was defined as any grade ≥3 toxicity according to the Radiation Therapy Oncology Group criteria.
  
  
  RESULTS
  Forty-six consecutive patients were enrolled. In cohort A, 6 patients received the planned treatment with no DLT. In cohort B, 1 of 8 patients experienced a DLT. In cohort C, a DLT occurred in 2 of 6 patients and therefore, a cohort expansion was required. Three of 16 patients treated at this dose level experienced a DLT. In addition, cohort D was expanded and DLT was found in 4 of 16 patients. Therefore, the maximal tolerated dose was not exceeded at any treatment level.
  
  
  CONCLUSIONS
  An intensified regimen of chemoradiotherapy delivering raltitrexed and oxaliplatin concurrently with concomitant boost radiotherapy (55 Gy/5 wk) can be safely administered in patients with locally advanced rectal cancer. On the basis of these results, this intensified regimen could be tested in a phase II study.
authors.affiliation: Department of Radiation Oncology, John Paul II Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Rome, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Caravatta
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Picardi
authors.forename: Rosa
authors.initials: R
authors.lastname: Tambaro
authors.forename: Gilbert D A
authors.initials: GD
authors.lastname: Padula
authors.forename: Gabriella
authors.initials: G
authors.lastname: Macchia
authors.forename: Francesco
authors.initials: F
authors.lastname: Deodato
authors.forename: Mariangela
authors.initials: M
authors.lastname: Massaccesi
authors.forename: Fabio
authors.initials: F
authors.lastname: Pacelli
authors.forename: Stefano
authors.initials: S
authors.lastname: Berardi
authors.forename: Marco Pericoli
authors.initials: MP
authors.lastname: Ridolfini
authors.forename: Loredana
authors.initials: L
authors.lastname: Di Filippo
authors.forename: Giovanni
authors.initials: G
authors.lastname: Fabrizio
authors.forename: Marcello
authors.initials: M
authors.lastname: Ingrosso
authors.forename: Numa
authors.initials: N
authors.lastname: Cellini
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.forename: Alessio G
authors.initials: AG
authors.lastname: Morganti
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D010534:Peritoneal Neoplasms / Q000188:drug therapy* / Q000556:secondary; D011799:Quinazolines / Q000008:administration & dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013876:Thiophenes / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; C068874:raltitrexed