Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study

Paoli, Antonino De; Chiara, Silvana; Luppi, Gabriele; Friso, Maria Luisa; Beretta, Giordano Domenico; Prete, S. Del; Pasetto, Lara Maria; Santantonio, M.; Sarti, Enrico; Mantello, G.; Innocente, R.; Frustaci, S.; Corvò, Renzo; Rosso, Riccardo

doi:10.1093/annonc/mdj041

Cited by 116 publications

(82 citation statements)

References 32 publications

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“…At the time of writing, there were two published phase II trials of capecitabine CRT (De Paoli, 2006;Krishnan et al, 2006) and a further study comparing capecitabine CRT to 5FU/LV (Kim et al, 2007), and all three used the 825 mg m À2 continuous daily schedule. In these studies, the number of patients receiving the full dose of capecitabine was much lower compared to our 5-day schedule.…”

Section: Discussionmentioning

confidence: 99%

Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer

et al. 2007

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There is increasing evidence supporting the use of preoperative chemoradiotherapy in patients with locally advanced rectal cancer in an attempt to facilitate complete surgical resection with clear margins. We describe our experience of using a 5-day per week regime of preoperative capecitabine chemoradiotherapy. Between November 2004 and September 2006, 70 patients with MRI-defined locally advanced rectal cancer were selected for treatment. Capecitabine was given at a dose of 900 mg m À2 for 5 days per week combined with 45 Gy of radiotherapy in 25 doses. This regime was well tolerated with 89% of our patients receiving the full dose of chemotherapy and 96% receiving the full dose of radiotherapy. Ninety-three per cent proceeded to macroscopically complete surgical resection. The pathological complete response rate was 9.2% with a node-negative rate of 66%. A negative circumferential margin was achieved by 79% of the patients who underwent resection. Compared to studies using a 7-day per week capecitabine schedule, our results show increased compliance and less dose reductions with comparable pathological outcome. There is clear evidence from two systematic reviews that adjuvant radiotherapy reduces the risk of local recurrence in patients with resectable rectal cancer (Camma et al, 2000; Colorectal Cancer Collaborative, 2001). The greatest benefit is seen when preoperative radiotherapy is used with a biologically equivalent dose of 430 Gy. Further clinical trials were required to assess the benefit of adding concurrent chemotherapy to preoperative radiotherapy.The recent publication of two phase III trials confirms that preoperative concurrent chemoradiation (CRT) is superior to long-course radiotherapy alone in patients with T3/4 or nodepositive resectable rectal cancer. The EORTC 22921 (Bosset et al, 2005) and FFCD 9203 (Gerard et al, 2006) trials compared intravenous 5-fluorouracil (5FU) and leucovorin (LV) given during the first and fifth weeks of radiotherapy with radiotherapy alone (dose of RT was 45 Gy in 25 fractions in both arms of the studies). Both trials demonstrated a reduction in the rates of local recurrence at 5 years from 17% with radiotherapy alone to 8 -9% with preoperative CRT, but neither trial showed any difference in overall survival. A further recent phase III trial has demonstrated that preoperative 5FU CRT is superior to post-operative CRT with a significant reduction in local recurrence from 12 to 6% as well as a significant reduction in both acute and long-term toxicity (Sauer et al, 2004). This evidence will clearly result in an increasing use of fluoropyrimidine-based CRT.Intravenous 5FU-based chemoradiation presents many logistical challenges. Continuous infusion of 5FU requires the insertion of a central venous line with its attendant risks of thrombosis and infection as well as the inconvenience of a portable infusion pump. The use of the bolus 5FU/LV regimen used in the EORTC and FFCD trials requires 10 daily visits to the chemotherapy day unit, with associated waiting time, t...

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Section: Discussionmentioning

confidence: 99%

Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer

et al. 2007

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“…Using the pCRT approach, the rate of local recurrence at 5-year ranges from 6 to 8%, 1,2 and the rate of complete pathological response ranges from 4 to 44% of cases, as reported in single institution series trials, 3,4 in phase II studies [5][6][7] and in randomized trials. 2,8 For patients with good pathologic response to pCRT, the oncological outcome has been reported to be better for 'responders' than for 'nonresponders'.…”

Section: Introductionmentioning

confidence: 94%

“…6,20 In brief, patients underwent to external beam RT with a 10-18 MV linear accelerator. The clinical target volume included the primary tumor, with the mesorectum, the posterior walls of the bladder and prostate/vagina, and the internal iliac nodes.…”

Section: Study Design and Patients Enrollmentmentioning

confidence: 99%

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

et al. 2010

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The aim of the study was the identification of a pharmacogenetic profile predictive of the tumor regression grade (TRG), considered as tumor response parameter, after neo-adjuvant treatment in rectal cancer patients. A total of 238 rectal cancer patients treated in a neo-adjuvant setting by a fluoropyrimidines-based chemo-radiotherapy (RT) were genotyped for 25 genetic polymorphisms in 16 genes relevant for treatment-associated pathways. Two polymorphisms were associated with TRG in a multivariate analysis: hOGG1-1245C4G, which can affect radiosensitivity and MTHFR-677C4T, which is involved in fluoropyrimidines action. Patients bearing at least one variant allele had a lower chance to get TRGp2 (OR ¼ 0.46 95% CI 0.23-0.90, P ¼ 0.024; and OR ¼ 0.48 95% CI 0.24-0.96, P ¼ 0.034; respectively). An association trend was observed for ABCB1-3435C4T, which is responsible for the multi-drug resistance (odds ratio (OR) ¼ 1.96, 95% confidence interval (CI) 0.98-3.95, P ¼ 0.057). Exploratory classification and regression tree (CART) analysis highlighted high-order gene-gene and gene-environment interactions and a genetic signature associated with differential response, with hOGG1-1245C4G as the most predictive factor. Other significant variables were: ABCB1-3435C4T, MTHFR-677C4T, ERCC1-8092C4A, ABCC2-1249G4A, XRCC1-28152G4A, XRCC3-4541A4G and patients gender. On the basis of CART results, patients were categorized into three groups according to tumor response probability: intermediate and high profiles had a higher probability to get TRGp2 as compared with low profiles (OR ¼ 4.12 95% CI 1. Po0.001 and OR ¼ 12.44, Po0.0001, respectively). This study evidences a major role of hOGG1-1245C4G and MTHFR-677C4T polymorphisms in the tumor response of rectal cancer patients treated with chemo-RT in neo-adjuvant setting, and shows the relevance of gene-gene and gene-environment interactions for complex phenotypes as tumor response.

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“…Due to limited follow-up time, no conclusion regarding the efficacy of the regimen can be made at this time. However, phase III evidence from other disease settings show equivalence of capecitabine to infusional 5-FU in multiple settings [18,24,25]. One randomized head-to-head study of infusional 5-FU versus capecitabine in combination with radiation for stage II/III rectal cancer demonstrated equivalent efficacy and toxicity when given with pelvic radiation at doses of 50.4 Gy over 28-31 days [16,17].…”

Section: Radiation Therapymentioning

confidence: 99%

“…Capecitabine (Cap) is an oral fluoropyrimidine shown to be equivalent to infusional 5-FU when given concurrently with pelvic irradiation in the neo-adjuvant treatment of rectal adenocarcinoma [16][17][18]. Unlike 5-FU, which is intravenously infused, Cap is orally administered which provides resource benefits as it is more convenient for patients and staff and does not require the use of a central venous infusional device.…”

Section: Introductionmentioning

confidence: 99%

Chemoradiation with Capecitabine and Mitomycin-C for Stage I-III Anal Squamous Cell Carcinoma

Kennecke¹

2016

CTOIJ

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Background: Standard therapy for patients with stage I-III squamous cell carcinoma (SCC) of the anal canal is chemo-radiotherapy with 5-fluorouracil (5-FU) and mitomycin C (MMC). While there is limited published evidence to substitute capecitabine (CAP) for 5-FU, the objectives of the study were to describe the toxicity, dose intensity and outcomes of a sequential cohort of patients treated with chemo-radiotherapy with CAP and MCC in a population-based setting. Methods: Patients with stage I-III malignancies of the anal canal referred between February 2010 and March 2012 were included. Dose intensity was calculated by comparing delivered versus planned radiation and chemotherapy treatments and toxicity was retrospectively graded according to standard protocol-specified criteria. Results: Among 66 eligible patients, median planned dose of radiation was 51.9 Gy over 5.5 weeks, range 25.0 to 63 Gy, and dose intensity was 98%. Median delivered dose of MCC delivered was 12 mg/m 2 on day one, week one while median CAP dose was 825 mg/m 2 twice daily on radiation days. CAP dose reductions due to toxicity were recorded for 13 patients (20%). Median follow-up was 20 months and 94% of patients with squamous cell histology had no evidence of relapse.

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Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study

Abstract: Preoperative chemoradiation with capecitabine and RT appeared to be effective in locally advanced resectable, rectal cancer. The favorable safety profile of the combination might warrant the use of capecitabine and RT with other effective new drugs.

Cited by 116 publications

References 32 publications

Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer

Preoperative radiotherapy combined with 5 days per week capecitabine chemotherapy in locally advanced rectal cancer

Tumor response is predicted by patient genetic profile in rectal cancer patients treated with neo-adjuvant chemo-radiotherapy

Chemoradiation with Capecitabine and Mitomycin-C for Stage I-III Anal Squamous Cell Carcinoma

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