title: Ten years of preoperative chemoradiation for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, and sphincter preservation in three consecutive studies.
abstract: OBJECTIVE
  To compare acute toxicity, tumor response, and sphincter preservation in three schedules of concurrent chemoradiation in resectable transmural and/or node-positive extraperitoneal rectal cancer.
  
  
  METHODS
  Between 1990 and 1999, 163 consecutive patients were treated according to the following combined modalities: FUMIR: between 1990 and 1995, 83 patients were treated with bolus i.v. mitomycin C (MMC), 10 mg/m(2) day 1, plus 24-h continuous infusion i.v. 5-fluorouracil (5-FU) 1,000 mg/m(2) days 1-4, and concurrent external beam radiotherapy (37.8 Gy). PLAFUR-4: between 1995 and 1998, 40 patients were treated with cisplatin (c-DDP) 60 mg/m(2) given as slow infusion (1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-4 and 29-32 with concurrent external-beam radiotherapy (50.4 Gy). PLAFUR-5: between 1998 and 1999, 40 patients were treated with c-DDP 60 mg/m(2) given as slow infusion (during 1-4 h) on days 1 and 29, plus 24-h continuous infusion i.v. 5-FU 1,000 mg/m(2), days 1-5 and 29-33 with concurrent external-beam radiotherapy (50.4 Gy).
  
  
  RESULTS
  Grade > or = 3 acute toxicity occurred in 14%, 5%, and 17% of patients treated in the FUMIR, PLAFUR-4, and PLAFUR-5 studies, respectively (p = 0.201). In the FUMIR, PLAFUR-4, and PLAFUR-5 studies, clinical response rate was 77%, 70%, and 83%, respectively. Tumor downstaging occurred in 57%, 68%, and 58% of patients, respectively. Pathologic complete response was recorded in 9% (FUMIR), 23% (PLAFUR-4), and 20% (PLAFUR-5) of patients. Sphincter-preserving surgery was feasible in 44% (FUMIR), 40% (PLAFUR-4), and 61% (PLAFUR-5) of patients having a distance between the anal-rectal ring and the lower pole of the tumor of 0-30 mm, and in 95%, 100%, and 100%, respectively, in those having a distance of 31-50 mm. Comparing FUMIR vs. PLAFUR, the clinical response rate was similar in the two series: a partial response was observed in 62/81 (77%) patients with FUMIR treatment, and in 61/80 (76%) patients with PLAFUR treatment. Tumor downstaging was observed in 46/81 (57%) patients and in 50/80 (68%) patients, respectively. The pathologic complete response rate was statistically higher in the PLAFUR series: 7/81 (9%) patients with FUMIR treatment and 17/80 (21%) patients with PLAFUR treatment (p = 0.04). Major downstaging (pT0+ pTmic+ pT1) in the FUMIR group was reported in 12/81 (15%) patients versus 31/80 (39%) patients in the PLAFUR group (p = 0.0006). The anal sphincter was preserved in 63/81 (78%) patients with FUMIR treatment and in 69/80 (86%) patients with PLAFUR treatment. The perioperative morbidity was statistically lower with PLAFUR: a perioperative morbidity was experienced by 20/81 (25%) patients with FUMIR treatment and by 9/80 (11%) patients with PLAFUR treatment (p = 0.042).
  
  
  CONCLUSIONS
  In our experience, higher radiation dose (50.4 Gy vs. 37.8 Gy), a second course of concurrent 5-FU, and the use of c-DDP instead of MMC improved the pathologic response rate without increasing acute toxicity and perioperative morbidity. The use of 5-FU 5-day infusion (PLAFUR-5) resulted in higher toxicity with a similar response rate compared to 4-day infusion (PLAFUR-4).
authors.affiliation: Cattedra di Radioterapia, Università Cattolica S. Cuore, Rome, Italy. vvalenti@rm.unicatt.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 C
authors.initials: MC
authors.lastname: Fares
authors.forename: M E
authors.initials: ME
authors.lastname: Rosetto
authors.forename: G
authors.initials: G
authors.lastname: Mantini
authors.forename: A G
authors.initials: AG
authors.lastname: Morganti
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 / Q000009:adverse effects*; D003131:Combined Modality Therapy; D003967:Diarrhea / Q000209:etiology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007970:Leukopenia / Q000209:etiology; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage / Q000009:adverse effects; D009367:Neoplasm Staging; D018579:Patient Selection; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D016685:Mitomycin; D005472:Fluorouracil