Preoperative (preop) radiotherapy (RT) ± 5 FU/folinic acid (FA) in T3–4 rectal cancers: results of the FFCD 9203 randomized trial

Conroy, Thierry; Bonnetain, F.; Chapet, O.; Bouché, Olivier; Dejardin, M. T. Closon; Untereiner, M.; Leduc, Bernard; François, Ετιεννε; Bosset, Jean-François; Gérard, Jean-Pierre

doi:10.1200/jco.2005.23.16_suppl.3504

Cited by 59 publications

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“…The importance of chemotherapy has been recently underlined by the results of two randomised trials. They demonstrated that 5FU associated to radiotherapy reduced the rate of local failure, at least in patients who had suboptimal surgery because the trials were initiated before TME had been systematically applied (Bosset et al, 2005;Gerard et al, 2005). 5-Flurouracil has been the mainstay of combined chemoradiotherapy in all large randomised trials (Bosset et al, 2004(Bosset et al, , 2005Sauer et al, 2004).…”

Section: Discussionmentioning

confidence: 99%

“…Since the introduction of total mesorectal excision (TME) which includes the resection of the entire mesorectal fascia, local recurrences are reported in 5 -17% of the patients, depending on the experience of the centre, of the surgeon and whether neoadjuvant treatment has been applied or not (Janjan et al, 1998;Kockerling et al, 1998;Kapiteijn et al, 2001;Glimelius et al, 2003;Bosset et al, 2005;Engel et al, 2005;Gerard et al, 2005;Marijnen et al, 2005). This is in sharp contrast to former conventional surgery without additional treatment options, which were associated with local recurrence rates of up to 40% (Pahlman and Glimelius, 1990;MacFarlane et al, 1993).…”

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confidence: 99%

“…Over the past years, emphasis was put on neoadjuvant chemoradiation followed by optimised surgery. It includes all three modalities -surgery, radiotherapy and chemotherapy, albeit variable in sequence and combination (Swedish Rectal Cancer Trial, 1997;Kapiteijn et al, 2001;Bosset et al, 2005;Gerard et al, 2005).…”

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

et al. 2006

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Patients with rectal cancer are at high risk of disease recurrence despite neoadjuvant radiochemotherapy with 5-Fluorouracil (5FU), a regimen that is now widely applied. In order to develop a regimen with increased antitumour activity, we previously established the recommended dose of neoadjuvant CPT-11 (three times weekly 90 mg m À2 ) concomitant to hyperfractionated accelerated radiotherapy (HART) followed by surgery within 1 week. Thirty-three patients (20 men) with a locally advanced adenocarcinoma of the rectum were enrolled in this prospective phase II trial (1 cT2, 29 cT3, 3 cT4 and 21 cN þ ). Median age was 60 years (range 43 -75 years). All patients received all three injections of CPT-11 and all but two patients completed radiotherapy as planned. Surgery with total mesorectal excision (TME) was performed within 1 week (range 2 -15 days). The preoperative chemoradiotherapy was overall well tolerated, 24% of the patients experienced grade 3 diarrhoea that was easily manageable. At a median follow-up of 2 years no local recurrence occurred, however, nine patients developed distant metastases. The 2-year disease-free survival was 66% (95% confidence interval 0.48 -0.83). Neoadjuvant CPT-11 and HART allow for excellent local control; however, distant relapse remains a concern in this patient population.

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Section: Discussionmentioning

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

et al. 2006

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“…Most current CRT schedules combine pelvic radiation with either continuous infusion of 5-fluorouracil (5FU), or 5FU modulated by LV. Mature results from the EORTC 22921 and FFCD 9203 trials of operable T3/T4 rectal cancer have recently demonstrated a convincing reduction in locoregional failure when a CRT regimen of 5FU and LV is added to 45 Gy of pelvic radiation over radiotherapy alone (Bosset et al, 2005a, b;Gerard et al, 2005). As the EORTC 22921 and FFCD 9203 trials used daily 5FU LV based CRT schedules, at the time the present study was designed, it was a logical step to develop preoperative radiation schedules that incorporated the addition of irinotecan to the same regimen.…”

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confidence: 99%

“…The present study aimed to evaluate the toxicity and efficacy of the addition of a 5-day schedule of irinotecan to a regimen of chemoradiation that uses 5FU and LV daily during the first and fifth weeks of pelvic radiation (45 Gy) as used in the EORTC 22921 and FFCD 9203 phase III trials (Bosset et al, 2005a, b;Gerard et al, 2005).…”

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A phase I/II study of irinotecan when added to 5-fluorouracil and leucovorin and pelvic radiation in locally advanced rectal cancer: a Colorectal Clinical Oncology Group Study

et al. 2007

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The objective of this study was to evaluate the maximum tolerated dose (MTD) and recommended dose of irinotecan administered as a 5-day schedule synchronously with 5-fluorouracil (5FU), leucovorin (LV) and preoperative pelvic radiation (45 Gy) for primary borderline/unresectable, locally advanced rectal cancer. The study used escalating doses of intravenous irinotecan (6, 8, 10, 12, 14, 16, 18, and 20 mg m À2 ) administered on days 1 -5 and 29 -33 followed by low dose LV (20 mg m À2 ) and 5FU (350 mg m À2 over 1 h) in sequential cohorts. Preoperative pelvic radiotherapy using a three-or four-field technique and megavoltage photons comprised 45 Gy given in 25 fractions, 1.8 Gy per fraction. Surgery in the form of mesorectal excision was performed 6 -10 weeks later. Histopathological examination of the resected specimen was performed according to techniques of Quirke, and compared with clinical staging. A distance of 1 mm or less between the peripheral extent of the tumour and the radial resection margin defined an involved circumferential resection margin (CRM). The MTD was determined as the dose causing more than a third of patients to have a dose-limiting toxicity (DLT) defined as specific grade 3 or 4 toxicities. Once the MTD was reached, a further 14 patients were treated at the dose level below the MTD. In total, 57 patients received irinotecan at the eight dose levels. The final cohort reached DLT after only four patients had been enrolled. The median age was 62 years (range 26 -75), 37 male and 20 female subjects. The MTD of irinotecan in this schedule was 20 mg m À2 when three out of four patients experienced DLT. Dose limiting grade 3 or 4 diarrhoea was reported in seven out of 57 patients, three at the 20 mg m À2 dose level. Serious haematological toxicity (grade 3) was minimal and reported in only three patients; one grade 3 neutropaenia, one grade 4 neutropaenia and one grade 3 febrile neutropaenia and anaemia. Compliance was good with 93 and 89% of patients completing radiotherapy and chemotherapy, respectively. The remaining patients had only minor deviations from protocol therapy. Eight patients did not proceed to surgery, in six cases because they remained unresectable or had developed metastatic disease, one patient was unfit for surgery and one died as a result of complications from radiotherapy. Forty-nine patients underwent a potentially curative surgical resection. Histopathological examination of the resected specimen demonstrated pCR 12 out of 49 (24%) and 12 out of 57 (21%) overall. A histologically confirmed clear circumferential resection margin (CRM) was achieved in 39 out of 49 (80%) of those resected, and 39 out of 57 (68%) overall. In conclusion, MTD with this scheduled regimen of irinotecan is 20 mg m À2 (days 1 -5 and 29 -33). The acceptable toxicity and compliance at 18 mg m À2 recommend testing this dose in future phase III studies. The tumour downstaging and complete resection rates (negative CRM) are encouragingly high for this very locally advanced group.

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Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma

Wong

Tandan

Silva

et al. 2007

Cochrane Database of Systematic Reviews

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Preoperative (preop) radiotherapy (RT) ± 5 FU/folinic acid (FA) in T3–4 rectal cancers: results of the FFCD 9203 randomized trial

Cited by 59 publications

References 0 publications

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

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

A phase I/II study of irinotecan when added to 5-fluorouracil and leucovorin and pelvic radiation in locally advanced rectal cancer: a Colorectal Clinical Oncology Group Study

Pre-operative radiotherapy and curative surgery for the management of localized rectal carcinoma

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