title: Preoperative chemoradiation with cisplatin and 5-fluorouracil for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, sphincter preservation.
abstract: OBJECTIVE
  To evaluate the impact of preoperative external radiation therapy intensified by systemic chemotherapy including bolus cisplatin (c-DDP) and 4-day infusional 5-fluorouracil (PLAFUR-4) on tumor response and sphincter preservation in patients with extraperitoneal T3 rectal cancer with acceptable toxicity, and to compare the results to our previous experience with bolus mitomycin c (MMC) and 4-day infusion 5-FU (FUMIR).
  
  
  METHODS
  Between October 1995 and March 1998, 40 consecutive patients with resectable extraperitoneal adenocarcinoma of the rectum were treated with preoperative chemoradiation: slow infusion i.v. c-DDP, 60 mg/m2, day 1 and 29 plus 24-h continuous infusion i.v. 5-fluorouracil (5-FU) 1000 mg/m2, days 1-4 and 29-32, and concurrent external beam radiotherapy (45 Gy whole pelvis followed by 5.4 Gy boost). All but 3 patients had T3 disease. Surgery was performed 6-8 weeks after the end of chemoradiation.
  
  
  RESULTS
  No patient had Grade 4 acute toxicity. Grade 3 hematological toxicity was observed only in 2 (5%) patients. No patient had major gastrointestinal, skin, or urological acute toxicity. All patients had radical surgery. There was no perioperative mortality; perioperative morbidity rate was 12%. Overall, 23% (9 of 40) of patients had a complete pathological response and 10% (4 of 40) of patients had rare isolated residual cancer cells (Tmic). Comparing the stage at the diagnostic workup with the pathological stage, tumor downstaging was observed in 27 (68%) patients; nodal status downstaging was detected in 24 (60%) patients. Thirty-four (85%) patients had a sphincter-saving surgical procedure. In 4 of 10 (40%) patients who were definitive candidates for an abdominoperineal resection (APR), the sphincter was preserved, as it was in 13 of 13 (100%) probable candidates. Lengthening of the distance between the anorectal ring and the lower pole of the tumor > or =20 mm was observed in 9 (23%) patients. None of the patients had soilage after the sphincter-saving procedure. In our previous experience with FUMIR the complete pathological response was 9%, the sphincter-saving surgical procedure was performed in 66% cases, and the Grade 3+ toxicity was observed in 13% of patients.
  
  
  CONCLUSIONS
  The addition of c-DDP to 5-FU (PLAFUR-4) in a neoadjuvant radiochemotherapy schedule improved the pathological response rate in comparison with our previous experience. Toxicity was low indeed, thus we commenced another study adding one more day of 5-FU infusion (PLAFUR-5) to further improve our results.
authors.affiliation: Divisione di Radioterapia, Università Cattolica S. Cuore, Rome, Italy. vi.valentini@agora.stm.it
authors.forename: V
authors.initials: V
authors.lastname: Valentini
authors.forename: C
authors.initials: C
authors.lastname: Coco
authors.forename: N
authors.initials: N
authors.lastname: Cellini
authors.forename: A
authors.initials: A
authors.lastname: Picciocchi
authors.forename: M E
authors.initials: ME
authors.lastname: Rosetto
authors.forename: G
authors.initials: G
authors.lastname: Mantini
authors.forename: L
authors.initials: L
authors.lastname: Marmiroli
authors.forename: B
authors.initials: B
authors.lastname: Barbaro
authors.forename: S
authors.initials: S
authors.lastname: Cogliandolo
authors.forename: G
authors.initials: G
authors.lastname: Nuzzo
authors.forename: M
authors.initials: M
authors.lastname: Tedesco
authors.forename: F
authors.initials: F
authors.lastname: Ambesi-Impiombato
authors.forename: M
authors.initials: M
authors.lastname: Cosimelli
authors.forename: M
authors.initials: M
authors.lastname: Rotman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001003:Anal Canal / Q000601:surgery; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003131:Combined Modality Therapy; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D002945:Cisplatin; D005472:Fluorouracil