title: Phase I study of postoperative radiotherapy with concomitant weekly irinotecan, 5- fluorouracil and folinic acid in locally advanced rectal cancer.
abstract: OBJECTIVE
  5- fluorouracil (5-FU)-based chemotherapy with concomitant pelvic radiotherapy represents the gold standard of the adjuvant treatment of high-risk rectal cancer. This study aimed to determine the maximum tolerated dose (MTD) of weekly irinotecan (CPT-11) when combined with fixed 5FU/FA doses and pelvic irradiation.
  
  
  METHODS
  Twenty- four patients with stage II or III rectal cancer were accrued. All had undergone curative surgery before entering the study. Standard pelvic radiotherapy was delivered (50.4 Gy, 1.8 Gy/ fraction in 5.5 weeks). The 5-FU/FA doses were 350/250 (mg/m(2)) in the first 6 patients and 250/100 in the remaining patients. Weekly doses of CPT-11 started at 30 mg/m(2) with escalation steps of 10 mg/m(2). CPT-11 was escalated when 3 patients had been monitored for 8 weeks, without a dose limiting toxicity (DLT).
  
  
  RESULTS
  Twenty-three out of 24 patients completed the chemoradiation course. Only 1 patient discontinued the treatment due to persistent grade 3 diarrhea. Of the 144 planned weekly chemotherapy cycles, only 7 were omitted as a result of persisting grade 2-3 gastrointestinal toxicity in 3 patients and grade 3 neutropenia in 1 patient. Grade 3 gastrointestinal DLTs were observed at doses at the level of 30/250/100 in 1 patient and 70/250/100 in 2 patients. Late DLTs were severe radiation dermatitis and colitis at 40/ 350/250 (1 patient) and 70/250/100 (2 patients), respectively. With a follow-up of 18 months 20 (83.3%) patients remain disease- free.
  
  
  CONCLUSIONS
  The administration of weekly CPT-11/ 5FU/FA with concomitant pelvic radiotherapy is feasible and effective. This treatment schedule is associated with mild myelosuppression and mild to moderate gastrointestinal toxicity. Caution should be paid on late radiotherapy-induced toxicities. The MTD of weekly CPT-11 is 30 mg/m(2) when combined with 5FU/FA doses (mg/m(2)) of 350sol;250 and reaches 60 mgsol;m(2) with lower doses of 5FU/FA (250/100).
authors.affiliation: First Department of Medical Oncology, Oncology, Metaxa Cancer Hospital, Piraeus, Greece.
authors.forename: N
authors.initials: N
authors.lastname: Ziras
authors.forename: P
authors.initials: P
authors.lastname: Tsoutsou
authors.forename: N
authors.initials: N
authors.lastname: Koliarakis
authors.forename: N
authors.initials: N
authors.lastname: Magdalinos
authors.forename: G
authors.initials: G
authors.lastname: Sarris
authors.forename: A
authors.initials: A
authors.lastname: Potamianou
authors.forename: M
authors.initials: M
authors.lastname: Paraskevaides
authors.forename: M
authors.initials: M
authors.lastname: Synodinou
authors.forename: K
authors.initials: K
authors.lastname: Chrysanthou
authors.forename: P
authors.initials: P
authors.lastname: Karageorgis
authors.forename: A E
authors.initials: AE
authors.lastname: Athanassiou