title: Neoadjuvant systemic fluorouracil and mitomycin C prior to synchronous chemoradiation is an effective strategy in locally advanced rectal cancer.
abstract: This study was designed to evaluate the benefits of neoadjuvant chemotherapy prior to chemoradiation and surgery in patients with locally advanced rectal cancer. Patients with previously untreated primary rectal cancer, reviewed in a multidisciplinary meeting and considered to have locally advanced disease on the basis of physical examination and imaging (MRI+CT n=30, CT alone n=6), were recruited. Patients received protracted venous infusion 5-FU (300 mg m(-2) day(-1) for 12 weeks) with mitomycin C (MMC) (7 mg m(-2) i.v. bolus every 6 weeks). Starting on week 13, 5-FU was reduced to 200 mg m(-2) day(-1) and concomitant pelvic radiotherapy 45 Gy in 25 fractions was commenced followed by 5.4-9 Gy boost to tumour bed. Surgery was planned 6 weeks after chemoradiation. Postoperatively, patients received 12 weeks of MMC and 5-FU at the same preoperative doses. Between January 99 and August 01, 36 eligible patients were recruited. Median age was 63 years (range=40-85). Following neoadjuvant chemotherapy, radiological tumour response was 27.8% (one CR and nine PRs) and no patient had progressive disease. In addition, 65% of patients had a symptomatic response including improvement in diarrhoea/constipation (59%), reduced rectal bleeding (60%) and diminished pelvic pain/tenesmus (78%). Following chemoradiation, tumour regression occurred in 80.6% (six CRs and 23 PRs; 95% CI=64-91.8%) and only one patient still had an inoperable tumour. R0 resection was achieved in 28 patients (82%). When compared with initial clinical staging, the pathological downstaging rate in T and/or N stage was 73.5% and pathological CR was found in one patient. Neoadjuvant systemic chemotherapy as a prelude to synchronous chemoradiation can be administered with negligible risk of disease progression and produces considerable symptomatic response with associated tumour regression.
authors.affiliation: Department of Medicine, Royal Marsden Hospital, Sutton, Surrey, UK.
authors.forename: I
authors.initials: I
authors.lastname: Chau
authors.forename: M
authors.initials: M
authors.lastname: Allen
authors.forename: D
authors.initials: D
authors.lastname: Cunningham
authors.forename: D
authors.initials: D
authors.lastname: Tait
authors.forename: G
authors.initials: G
authors.lastname: Brown
authors.forename: M
authors.initials: M
authors.lastname: Hill
authors.forename: K
authors.initials: K
authors.lastname: Sumpter
authors.forename: A
authors.initials: A
authors.lastname: Rhodes
authors.forename: A
authors.initials: A
authors.lastname: Wotherspoon
authors.forename: A R
authors.initials: AR
authors.lastname: Norman
authors.forename: A
authors.initials: A
authors.lastname: Hill
authors.forename: A
authors.initials: A
authors.lastname: Massey
authors.forename: Y
authors.initials: Y
authors.lastname: Prior
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D003131:Combined Modality Therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D011183:Postoperative Complications; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy
chemical_list: D016685:Mitomycin; D005472:Fluorouracil