Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).

2.50
Hdl Handle:
http://hdl.handle.net/10541/85195
Title:
Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).
Authors:
Gollins, Simon W; Myint, S; Susnerwala, S; Haylock, B; Wise, M; Topham, C; Samuel, L; Swindell, Ric; Morris, J; Mason, L; Levine, Edward
Abstract:
BACKGROUND: The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. METHODS: Forty-six patients were recruited and treated on the basis that MRI scanning had shown poor-risk tumours with threatening (< or =1 mm) or involvement of the mesorectal fascia. Conformal RT was given using 3 or 4 fields at daily fractions of 1.8 Gy on 5 days per week to a total dose of 45 Gy. Concurrently oral capecitabine was given twice daily throughout radiotherapy continuously from days 1 to 35 and intravenous irinotecan was given once per week during weeks 1 to 4 of RT. Dose levels were gradually escalated as follows. Dose level 1: capecitabine 650 mg m(-2) b.i.d. and irinotecan 50 mg m(-2); Dose level 2: capecitabine 650 mg m(-2) b.i.d. and irinotecan 60 mg m(-2); Dose level 3: capecitabine 825 mg m(-2) b.i.d. and irinotecan 60 mg m(2); Dose level 4: capecitabine 825 mg m(-2) b.i.d. and irinotecan 70 mg m(-2). RESULTS: Diarrhoea (grade 3, no grade 4) was the main serious acute toxicity with lesser degrees of fatigue, neutropenia, anorexia and palmar-plantar erythrodysesthesia. The recommended dose for future study was dose level 2 at which 3 of 14 patients (21%) developed grade 3 diarrhoea. Postoperative complications included seven pelvic or wound infections and two anastomotic and two perineal wound dehiscences. There were no deaths in the first 30 days postoperatively. Of 41 resected specimens, 11 (27%) showed a pathological complete response (pCR) and five (12%) showed an involved circumferential resection margin (defined as < or =1 mm). The 3-year disease-free survival (intent-to-treat) was 53.2%. CONCLUSION: In patients with poor-risk MRI-defined locally advanced rectal cancer threatening or involving the mesorectal fascia, preoperative chemoradiation based on RT at 45 Gy in 25 daily fractions over 5 weeks with continuous daily oral capecitabine at 650 mg m(-2) b.i.d. days 1-35 and weekly IV irinotecan at 60 mg m(-2) weeks 1-4, provides acceptable acute toxicity and postoperative morbidity with encouraging response and curative resection rates.
Affiliation:
Department of Clinical Oncology, North Wales Cancer Treatment Centre, Rhyl LL18 5UJ, UK. simon.gollins@cd-tr.wales.nhs.uk
Citation:
Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2). 2009, 101 (6):924-34 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
15-Sep-2009
URI:
http://hdl.handle.net/10541/85195
DOI:
10.1038/sj.bjc.6605258
PubMed ID:
19690550
Type:
Article
Language:
en
ISSN:
1532-1827
Appears in Collections:
All Christie Publications ; Clinical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorGollins, Simon Wen
dc.contributor.authorMyint, Sen
dc.contributor.authorSusnerwala, Sen
dc.contributor.authorHaylock, Ben
dc.contributor.authorWise, Men
dc.contributor.authorTopham, Cen
dc.contributor.authorSamuel, Len
dc.contributor.authorSwindell, Ricen
dc.contributor.authorMorris, Jen
dc.contributor.authorMason, Len
dc.contributor.authorLevine, Edwarden
dc.date.accessioned2009-11-02T16:33:44Z-
dc.date.available2009-11-02T16:33:44Z-
dc.date.issued2009-09-15-
dc.identifier.citationPreoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2). 2009, 101 (6):924-34 Br. J. Canceren
dc.identifier.issn1532-1827-
dc.identifier.pmid19690550-
dc.identifier.doi10.1038/sj.bjc.6605258-
dc.identifier.urihttp://hdl.handle.net/10541/85195-
dc.description.abstractBACKGROUND: The aim of this study was to investigate the safety of neoadjuvant chemoradiation using radiotherapy (RT) combined with concurrent capecitabine and irinotecan for locally advanced rectal cancer before surgery. METHODS: Forty-six patients were recruited and treated on the basis that MRI scanning had shown poor-risk tumours with threatening (< or =1 mm) or involvement of the mesorectal fascia. Conformal RT was given using 3 or 4 fields at daily fractions of 1.8 Gy on 5 days per week to a total dose of 45 Gy. Concurrently oral capecitabine was given twice daily throughout radiotherapy continuously from days 1 to 35 and intravenous irinotecan was given once per week during weeks 1 to 4 of RT. Dose levels were gradually escalated as follows. Dose level 1: capecitabine 650 mg m(-2) b.i.d. and irinotecan 50 mg m(-2); Dose level 2: capecitabine 650 mg m(-2) b.i.d. and irinotecan 60 mg m(-2); Dose level 3: capecitabine 825 mg m(-2) b.i.d. and irinotecan 60 mg m(2); Dose level 4: capecitabine 825 mg m(-2) b.i.d. and irinotecan 70 mg m(-2). RESULTS: Diarrhoea (grade 3, no grade 4) was the main serious acute toxicity with lesser degrees of fatigue, neutropenia, anorexia and palmar-plantar erythrodysesthesia. The recommended dose for future study was dose level 2 at which 3 of 14 patients (21%) developed grade 3 diarrhoea. Postoperative complications included seven pelvic or wound infections and two anastomotic and two perineal wound dehiscences. There were no deaths in the first 30 days postoperatively. Of 41 resected specimens, 11 (27%) showed a pathological complete response (pCR) and five (12%) showed an involved circumferential resection margin (defined as < or =1 mm). The 3-year disease-free survival (intent-to-treat) was 53.2%. CONCLUSION: In patients with poor-risk MRI-defined locally advanced rectal cancer threatening or involving the mesorectal fascia, preoperative chemoradiation based on RT at 45 Gy in 25 daily fractions over 5 weeks with continuous daily oral capecitabine at 650 mg m(-2) b.i.d. days 1-35 and weekly IV irinotecan at 60 mg m(-2) weeks 1-4, provides acceptable acute toxicity and postoperative morbidity with encouraging response and curative resection rates.en
dc.language.isoenen
dc.subjectRectal Canceren
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshCamptothecin-
dc.subject.meshCombined Modality Therapy-
dc.subject.meshDeoxycytidine-
dc.subject.meshFemale-
dc.subject.meshFluorouracil-
dc.subject.meshHumans-
dc.subject.meshMagnetic Resonance Imaging-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshRectal Neoplasms-
dc.titlePreoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).en
dc.typeArticleen
dc.contributor.departmentDepartment of Clinical Oncology, North Wales Cancer Treatment Centre, Rhyl LL18 5UJ, UK. simon.gollins@cd-tr.wales.nhs.uken
dc.identifier.journalBritish Journal of Canceren

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