title: Concomitant boost radiotherapy and multidrug chemotherapy in the neoadjuvant treatment of locally advanced rectal cancer: results of a phase II study.
abstract: BACKGROUND
  An intensified multidrug chemotherapy regimen (raltitrexed plus oxaliplatin, Tom-Ox) plus concomitant boost radiotherapy, in the neoadjuvant treatment of locally advanced rectal cancer patients, was shown feasible in our previous study. The aim of this study was to evaluate the efficacy in terms of pathologic complete response to pre-operative therapy.
  
  
  METHODS
  A Phase II study was designed and clinical stage T3-T4 and/ or N ≥ 1 patients were treated with concomitant boost radiotherapy (55 Gy/5 weeks) plus concurrent chemotherapy (Tom-Ox). The primary endpoint was the assessment of efficacy in terms of clinical and pathologic response to pre-operative therapy. According to the Gehan's design study, 25 patients were enrolled. Toxicity was assessed according to the RTOG-EORTC and CTCAE v.3.0 criteria.
  
  
  RESULTS
  Twenty-five consecutive patients were treated. Twenty-two of the 25 (88%) patients had a partial clinical response at the time of pre-operative magnetic resonance imaging (MRI). Only one patient showed progressive systemic disease at pre-surgical revaluation and was subjected only to biopsy to evaluate pathological response. Twenty-four patients (96%) underwent surgery. Overall, pathologic complete response was observed in eight patients (32%; CI 0.95:12-55%) and only microscopic tumor foci (pTmic) in two patients (pT0-mic: 40%; CI 0.95:18-63%). Nineteen patients (76%) showed tumor down-staging. Proctitis and/or diarrhea were the most frequent acute side effects experienced. Eighteen patients had grade 1-2 toxicity (77%); whereas two patients experienced grade 3 toxicity (8%). Two-year Local control and actuarial Disease Free Survival were 100% and 91%, respectively. CONCLUSION. An intensified regimen of concomitant boost radiotherapy plus concurrent raltitrexed and oxaliplatin, can be safely administered in patients with locally advanced rectal cancer. This regimen produces high rates of pathological complete response. Based on available data, this type of treatment could be offered to patients with more advanced tumors (T4 or local recurrence).
authors.affiliation: Radiation Oncology Department, "John Paul II" Center for High Technology Research and Education in Biomedical Sciences, Catholic University, Campobasso, Italy.
authors.forename: Luciana
authors.initials: L
authors.lastname: Caravatta
authors.forename: Gilbert D A
authors.initials: GD
authors.lastname: Padula
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Picardi
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: Luigi
authors.initials: L
authors.lastname: Sofo
authors.forename: Fabio
authors.initials: F
authors.lastname: Pacelli
authors.forename: Fabio
authors.initials: F
authors.lastname: Rotondi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cecere
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sallustio
authors.forename: Liberato
authors.initials: L
authors.lastname: Di Lullo
authors.forename: Adele
authors.initials: A
authors.lastname: Piscopo
authors.forename: Samantha
authors.initials: S
authors.lastname: Mignogna
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Bonomo
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* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001706:Biopsy; D017024:Chemotherapy, Adjuvant; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D011878:Radiotherapy / Q000009:adverse effects; D018714:Radiotherapy, Adjuvant; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; C068874:raltitrexed