Preoperative downstaging chemoradiation with concurrent irinotecan and capecitabine in MRI-defined locally advanced rectal cancer: a phase I trial (NWCOG-2).
Authors
Gollins, Simon WMyint, S
Susnerwala, S
Haylock, B
Wise, M
Topham, C
Samuel, L
Swindell, Ric
Morris, J
Mason, L
Levine, Edward
Affiliation
Department of Clinical Oncology, North Wales Cancer Treatment Centre, Rhyl LL18 5UJ, UK. simon.gollins@cd-tr.wales.nhs.ukIssue Date
2009-09-15
Metadata
Show full item recordAbstract
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.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. CancerJournal
British Journal of CancerDOI
10.1038/sj.bjc.6605258PubMed ID
19690550Type
ArticleLanguage
enISSN
1532-1827ae974a485f413a2113503eed53cd6c53
10.1038/sj.bjc.6605258
Scopus Count
Related articles
- Preoperative chemoradiotherapy using concurrent capecitabine and irinotecan in magnetic resonance imaging-defined locally advanced rectal cancer: impact on long-term clinical outcomes.
- Authors: Gollins S, Sun Myint A, Haylock B, Wise M, Saunders M, Neupane R, Essapen S, Samuel L, Dougal M, Lloyd A, Morris J, Topham C, Susnerwala S
- Issue date: 2011 Mar 10
- A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer.
- Authors: Willeke F, Horisberger K, Kraus-Tiefenbacher U, Wenz F, Leitner A, Hochhaus A, Grobholz R, Willer A, Kähler G, Post S, Hofheinz RD
- Issue date: 2007 Mar 26
- 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.
- Authors: Glynne-Jones R, Falk S, Maughan TS, Meadows HM, Sebag-Montefiore D
- Issue date: 2007 Feb 26
- Preoperative chemoradiation with irinotecan and capecitabine in patients with locally advanced resectable rectal cancer: long-term results of a Phase II study.
- Authors: Hong YS, Kim DY, Lim SB, Choi HS, Jeong SY, Jeong JY, Sohn DK, Kim DH, Chang HJ, Park JG, Jung KH
- Issue date: 2011 Mar 15
- Concurrent chemoradiation with capecitabine and weekly irinotecan as preoperative treatment for rectal cancer: results from a phase I/II study.
- Authors: Klautke G, Küchenmeister U, Foitzik T, Ludwig K, Prall F, Klar E, Fietkau R
- Issue date: 2006 Apr 10