title: Oxaliplatin-containing Preoperative Therapy in Locally Advanced Rectal Cancer: Local Response, Toxicity and Long-term Outcome.
abstract: This non-randomised study was undertaken to examine oxaliplatin as possibly an intensifying component of sequential neoadjuvant therapy in locally advanced rectal cancer for improved local and metastatic outcome.
  
  
  
  Ninety-seven patients (57 T2-3 cases, 40 T4 cases) received two cycles of the Nordic FLOX regimen (oxaliplatin 85 mg/m(2) day 1 and bolus 5-fluorouracil 500 mg/m(2) and folinic acid 100 mg days 1 and 2) before long-course chemoradiotherapy with concomitant oxaliplatin and capecitabine, followed by pelvic surgery. Treatment toxicity, local tumour response and long-term outcome were recorded.
  
  
  
  Good histologic tumour regression was obtained in 72% of patients. Implementing protocol-specific dose adjustments, tolerance was acceptable and 95% of patients received the total prescribed radiation dose. Estimated 5 year progression-free and overall survival were 61% and 83%, respectively. T4 stage was associated with an inferior local response rate, which again was highly associated with impaired long-term outcome.
  
  
  
  In this cohort of rectal cancer patients dominated by T4 and advanced T3 cases given sequential oxaliplatin-containing preoperative therapy with acceptable toxicity, high tumour response rates and overall survival were obtained, consistent with both local and systemic effects. However, tumour response and long-term outcome remained inferior for a significant number of T4 cases, suggesting that the T4 entity is biologically heterogeneous with subgroups of patients eligible for further individualisation of therapy.
authors.affiliation: Department of Oncology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway. Electronic address: svedue@ous-hf.no.
authors.forename: S
authors.initials: S
authors.lastname: Dueland
authors.affiliation: Department of Oncology, Akershus University Hospital, Akershus, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: A H
authors.initials: AH
authors.lastname: Ree
authors.affiliation: Department of Pathology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: K K
authors.initials: KK
authors.lastname: Grøholt
authors.affiliation: Department of Tumour Biology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: M G
authors.initials: MG
authors.lastname: Saelen
authors.affiliation: Department of Tumour Biology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: S
authors.initials: S
authors.lastname: Folkvord
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Radiology & Nuclear Medicine, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: K H
authors.initials: KH
authors.lastname: Hole
authors.affiliation: Department of Radiology & Nuclear Medicine, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Seierstad
authors.affiliation: Department of Gastroenterological Surgery, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: S G
authors.initials: SG
authors.lastname: Larsen
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterological Surgery, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: K E
authors.initials: KE
authors.lastname: Giercksky
authors.affiliation: Department of Gastroenterological Surgery, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: J N
authors.initials: JN
authors.lastname: Wiig
authors.affiliation: Department of Tumour Biology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway; Department of Oncology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Boye
authors.affiliation: Department of Gastroenterological Surgery, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway; Department of Tumour Biology, Oslo University Hospital - Norwegian Radium Hospital, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Flatmark
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D000069287:Capecitabine / Q000008:administration & dosage / Q000009:adverse effects; D059248:Chemoradiotherapy / Q000009:adverse effects / Q000379:methods; D018450:Disease Progression; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil
keywords: 5-fluorouracil; chemoradiotherapy; locally advanced rectal cancer; neoadjuvant chemotherapy; oxaliplatin