Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study

Machiels, J.-P.; Duck, Lionel; Honhon, Brigitte; Coster, B M De; Coche, J.-C.; Scalliet, Pierre; Humblet, Yves; Aydın, Selda; Kerger, Joseph; Remouchamps, Vincent; Canon, J-L; Maele, P Van; Gilbeau, L.; Laurent, Stéphanie; Kirkove, C.; Octave-Prignot, M; Baurain, Jean‐François; Léonard, Daniel; Sempoux, Christine

doi:10.1093/annonc/mdi406

Cited by 119 publications

(48 citation statements)

References 31 publications

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“…However, the rate of grade III/IV toxicity (10%) noted in this study is comparable with that reported for oxaliplatin regimes (18 -30%) (Alonso et al, 2004(Alonso et al, , 2007Casado et al, 2004;Tucci et al, 2004;Fakih et al, 2005;Machiels et al, 2005;Avallone et al, 2006;Rutten et al, 2006;Rödel et al, 2007). Indeed, the findings of this study suggest a safety profile for irinotecan, 5-FU and radiotherapy that is comparable with previously reported findings with capecitabine and radiotherapy (rate of grade III/IV diarrhoea 12 -28%) (Mehta et al, 2003;Navarro et al, 2003;Mitchell et al, 2004;Mohiuddin et al, 2006;Willeke et al, 2007), but using a lower radiation dose (45 Gy as opposed to 50.4 Gy in the capecitabine regimen).…”

Section: Discussionsupporting

confidence: 88%

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study

et al. 2008

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In the UK, 10% of patients diagnosed with rectal cancer have inoperable disease at presentation. This study ascertained whether the resectability rate of inoperable locally advanced rectal cancer was improved by administration of intravenous irinotecan, 5-fluorouracil (5-FU) and pelvic radiotherapy. During phase I of the trial (n ¼ 12), the dose of irinotecan was escalated in three-patient cohorts from 50 mg m À2 to 60 mg m À2 to 70 mg m À2 to identify the maximum tolerated dose (60 mg m À2 ). In phase II, 31 patients with nonresectable disease received 45 Gy radiotherapy and 5-FU infusions (200 mg m À2 per day) for 5 weeks. Irinotecan (60 mg m À2 ) was given on days 1, 8, 15 and 22. After treatment, patients were operated on if possible. Thirty patients completed the protocol, 28 underwent surgery. Before surgery, MRI restaging of 24 patients showed that 19 (79%) had a reduction in tumour stage after treatment (seven complete clinical response and 12 partial). Of 27 patients followed up after surgery, 22 (81%) had clear circumferential resection margins. Disease-free and overall survival estimates at 3 years were 65 and 90%, respectively. The regimen was well tolerated. Irinotecan, 5-FU and radiotherapy results in tumour downgrading, allowing resection of previously inoperable tumour with acceptable toxicity.

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Section: Discussionsupporting

confidence: 88%

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study

et al. 2008

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“…The rate of grade 3 -4 diarrhoea reported in the CapIri-RT trials is about 15 -30% (Hofheinz et al, 2005;Gollins et al, 2006;Klautke et al, 2006). Using capecitabine and oxaliplatin combinations, grade 3 -4 diarrhoea is reported to range between 18% (n ¼ 85; CORE-trial; Rutten et al, 2006) and 30% (n ¼ 40; RadiOxCape-study; Machiels et al, 2005). In this cross-trial comparison neither CapIri-RT or CapOx-RT regimen seem to be advantageous although the use of different chemotherapy regimen, radiotherapy doses and a limited number of patients included in these trials preclude firmer conclusions.…”

Section: Discussionmentioning

confidence: 99%

A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer

et al. 2007

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We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial. Patients with rectal cancer clinical stages T3/4 Nx or N þ were recruited to receive irinotecan (50 mg m À2 weekly) and capecitabine (500 mg m À2 bid days 1 -38) with a concurrent RT dose of 50.4 Gy. Surgery was scheduled 4 -6 weeks after the completion of chemoradiation. A total of 36 patients (median age 62 years; m/f: 27:9) including three patients with local recurrence were enclosed onto the trial. The median distance of the tumour from the anal verge was 5 cm. The main toxicity observed was (NCI-CTC grades 1/2/3/4 (n)): Anaemia 23/9/À/À; leucocytopenia 12/7/7/2, diarrhoea 13/15/4/À, nausea/vomiting 9/10/2/À, and increased activity of transaminases 3/3/1/À. One patient had a reversible episode of ventricular fibrillation during chemoradiation, most probably caused by capecitabine. The relative dose intensity was (median/mean (%)): irinotecan 95/91, capecitabine 100/92). Thirty-four patients underwent surgery (anterior resection n ¼ 25; abdomino-perineal resection n ¼ 6; Hartmann's procedure n ¼ 3). R0-resection was accomplished in all patients. Two patients died in the postoperative course from septic complications. Pathological complete remission was observed in five out of 34 resected patients (15%), and nine patients showed microfoci of residual tumour (26%). After a median follow-up of 28 months one patient had developed a local recurrence, and five patients distant metastases. Three-year overall survival for all patients with surgery (excluding three patients treated for local relapse or with primary metastatic disease) was 80%. In summary, preoperative chemoradiation with CapIri-RT exhibits promising efficacy whereas showing managable toxicity. The local recurrence and distant failure rates observed after a median 28 months are low compared with standard 5-fluorouracil based therapy. Advances in surgical technique, including total mesorectal excision and thorough pathohistological work-up of the resected specimen have significantly improved the prognosis of patients with localised rectal cancer during the past two decades. Nevertheless, preoperative radiotherapy further improves local recurrence rates (Kapiteijn et al, 2001). The German CAO/AIO/ARO-94 trial, which compared pre-and postoperative chemoradiation in resectable rectal cancer, established the neoadjuvant approach as a new standard of care given it's superiority with respect to local failure rates and toxicity (Sauer et al, 2004). Moreover, the MRC CR07 trial, which compared short-course preoperative radiotherapy (5 Â 5 Gy) in resectable rectal cancer with selective postoperative chemoradiation in patients with compromised circumferential resection margins, showed a significant reduction in local recurrence and improved disease-free survival in favour of the short-course preoperative radiotherapy . Finally, bot...

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“…These include continuous capecitabine (7 days per week) with oxaliplatin given on days 1 and 29 (Glynne-Jones et al, 2006c), continuous capecitabine (5 days per week) with weekly doses of oxaliplatin (Machiels et al, 2005;Rutten et al, 2006) and discontinuous capecitabine (days 1 -14 and 22 -35) with oxaliplatin on days 1, 8, 22 and 29 (Roedel et al, 2003(Roedel et al, , 2007. The aim of the present multicentre phase II study was to evaluate the efficacy, tolerability and feasibility of preoperative capecitabine plus oxaliplatin in combination with radiotherapy as described by Roedel et al (2003Roedel et al ( , 2007, and to investigate the contribution of an additional single cycle of neoadjuvant capecitabine and oxaliplatin (XELOX regimen) (Díaz-Rubio et al, 2002;Cassidy et al, 2004) before the start of radiotherapy.…”

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confidence: 99%

Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer

et al. 2008

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This multicentre phase II study evaluated the efficacy and safety of preoperative capecitabine plus oxaliplatin and radiotherapy (RT) in patients with locally advanced rectal cancer (T3/T4 rectal adenocarcinoma with or without nodal involvement). Treatment consisted of one cycle of XELOX (capecitabine 1000 mg m À2 bid on days 1 -14 and oxaliplatin 130 mg m À2 on day 1), followed by RT (1.8 Gy fractions 5 days per week for 5 weeks) plus CAPOX (capecitabine 825 mg m À2 bid on days 22 -35 and 43 -56, and oxaliplatin 50 mg m À2 on days 22, 29, 43 and 50). Surgery was recommended 5 weeks after completion of chemoradiotherapy. The primary end point was pathological complete tumour response (pCR). Sixty patients were enrolled. In the intent-to-treat population, the pCR rate was 23% (95% CI: 13 -36%). 58 patients underwent surgery; R0 resection was achieved in 57 (98%) patients, including all 5 patients with T4 tumours. Sphincter preservation was achieved in 49 (84%) patients. Tumour and/or nodal downstaging was observed in 39 (65%) patients. The most common grade 3/4 adverse events were diarrhoea (20%) and lymphocytopaenia (43%). Preoperative capecitabine, oxaliplatin and RT achieved encouraging rates of pCR, R0 resection, sphincter preservation and tumour downstaging in patients with locally advanced rectal cancer.

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Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study

Abstract: Combination of preoperative radiotherapy with capecitabine and oxaliplatin is feasible for downstaging rectal cancer.

Cited by 119 publications

References 31 publications

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study

Irinotecan+5-fluorouracil with concomitant pre-operative radiotherapy in locally advanced non-resectable rectal cancer: a phase I/II study

A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer

Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer

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