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 ¼ 30, CT alone n ¼ 6), were recruited. Patients received protracted venous infusion 5-FU (300 mg m À2 day À1 for 12 weeks) with mitomycin C (MMC) (7 mg m À2 i.v. bolus every 6 weeks). Starting on week 13, 5-FU was reduced to 200 mg m À2 day À1 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 ¼ 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 ¼ 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.

CPT-11 and concomitant hyperfractionated accelerated radiotherapy induce efficient local control in rectal cancer patients: results from a phase II

“…Despite a relatively short interval between the end of chemoradiotherapy and surgery, downstaging was achieved in one third of the patients and in almost 80% of patients the resection was complete with negative margins (R0-resection). This compares favourably with other neoadjuvant treatment regimens (Klautke et al, 2001;Chau et al, 2003;Rodel et al, 2003).…”

MRI directed multidisciplinary team preoperative treatment strategy: the way to eliminate positive circumferential margins?

“…The debate over preoperative vs postoperative radiotherapy has been resolved (Sauer et al, 2004) and neoadjuvant therapy with either chemoradiation or long course chemotherapy has emerged as an effective treatment in the downstaging/downsizing of locally advanced tumours (Chau et al, 2003;Rodel et al, 2003). This has resulted in a greater proportion of patients being considered for curative resection (Janjan et al, 1999;Chau et al, 2003).…”

“…Starting on week 13, 5-FU was reduced to 200 mg m À2 day À1 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 (Chau et al, 2003).…”

“…Therefore, it has been our policy to proceed with surgery alone if MRI shows favourable prognostic features and to employ neoadjuvant chemoradiotherapy as a means of inducing regression in locally advanced rectal cancers (Janjan et al, 1999;Chau et al, 2003). The effectiveness of this approach can be judged by auditing the histological CRMÀve rates.…”

The Flow–Metabolic Phenotype of Primary Colorectal Cancer: Assessment by Integrated 18F-FDG PET/Perfusion CT with Histopathologic Correlation

“…However, although short-course preoperative radiotherapy and chemoradiation are effective strategies for locoregional control, they are not effective for systemic control, and they may not necessarily improve overall survival, as shown by the Dutch TME trial (3). This has led to the proposal of additional neoadjuvant chemotherapy to chemoradiation strategies in several phase II studies (Table 1) (6)(7)(8)(9). Neoadjuvant chemotherapy (fluoropyrimidine/oxaliplatin with or without panatimumab: 3 cycles of standard chemotherapy before surgery and 9 cycles after surgery) is also being explored for colon cancer ($stage III as defined by CT) in the FOxTROT study (fluoropyrimidine, oxaliplatin, and targeted receptor preoperative therapy for colon cancer) in the United Kingdom.…”