title: Biweekly oxaliplatin, raltitrexed, 5-fluorouracil and folinic acid combination chemotherapy during preoperative radiation therapy for locally advanced rectal cancer: a phase I-II study.
abstract: Oxaliplatin (OXA), raltitrexed (RTX), 5-fluorouracil (FU) and folinic acid (FA) have shown activity in metastatic colorectal cancer, radioenhancing effect and synergism when combined. We evaluated a chemotherapy (CT) combination of OXA, RTX and FU/FA during preoperative radiotherapy (RT) in locally advanced rectal cancer (LARC) patients. Fifty-one patients with LARC at high risk of recurrence (T4, N+ or T3N0 < or =5 cm from anal verge and/or circumferential resection margin < or =5 mm) received three biweekly courses of CT during pelvic RT (45 Gy). Surgery was planned 8 weeks after CT-RT. Recommended doses (RDs) determined during phase I were utilised in the subsequent phase II trial, where the rate of tumour regression grade (TRG) 1 or 2 was the main end point. No toxic deaths occurred, and severe toxicity was easily managed. In phase II, RDs delivered in 31 patients were OXA 100 mg m(-2) and RTX 2.5 mg m(-2) on day 1, and FU 900 mg m(-2) and LFA 250 mg m(-2) on day 2. Main severe toxicities by patients were grade 4 neutropenia (23%) and grade 3 diarrhoea (19%). In 71% (95% confidence limits, 52-86%) of patients, TRG1 (13) or TRG2 (9) was obtained. All patients are alive and recurrence-free after a median follow-up of 29 months. Combination of OXA, RTX and FU/FA with pelvic RT has an acceptable toxicity and a high clinical activity in LARC and should be studied further in patients at high risk of recurrence.
authors.affiliation: Department of Medical Oncology, National Tumour Institute, Naples, Italy. avalloneantonio@libero.it
authors.forename: A
authors.initials: A
authors.lastname: Avallone
authors.forename: P
authors.initials: P
authors.lastname: Delrio
authors.forename: C
authors.initials: C
authors.lastname: Guida
authors.forename: F
authors.initials: F
authors.lastname: Tatangelo
authors.forename: A
authors.initials: A
authors.lastname: Petrillo
authors.forename: P
authors.initials: P
authors.lastname: Marone
authors.forename: L G
authors.initials: LG
authors.lastname: Cascini
authors.forename: B
authors.initials: B
authors.lastname: Morrica
authors.forename: S
authors.initials: S
authors.lastname: Lastoria
authors.forename: V
authors.initials: V
authors.lastname: Parisi
authors.forename: A
authors.initials: A
authors.lastname: Budillon
authors.forename: P
authors.initials: P
authors.lastname: Comella
mesh_terms: D000230:Adenocarcinoma / Q000628:therapy*; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D015179:Colorectal Neoplasms / Q000628:therapy*; D013505:Digestive System Surgical Procedures; D004305:Dose-Response Relationship, Drug; 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; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D011300:Preoperative Care; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D013876:Thiophenes / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D009944:Organoplatinum Compounds; D011799:Quinazolines; D013876:Thiophenes; D000077150:Oxaliplatin; C068874:raltitrexed; D002955:Leucovorin; D005472:Fluorouracil