Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial.
AuthorChua, YJ; Barbachano, Y; Cunningham, D; Oates, JR; Brown, G; Wotherspoon, A; Tait, D; Massey, A; Tebbutt, NC; Chau, I
Source TitleLancet Oncol
University of Melbourne Author/sTebbutt, Niall
AffiliationSurgery - Austin Health And Northern Health
Document TypeJournal Article
CitationsChua, Y. J., Barbachano, Y., Cunningham, D., Oates, J. R., Brown, G., Wotherspoon, A., Tait, D., Massey, A., Tebbutt, N. C. & Chau, I. (2010). Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial.. Lancet Oncol, 11 (3), pp.241-248. https://doi.org/10.1016/S1470-2045(09)70381-X.
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C1 - Journal Articles Refereed
BACKGROUND: Patients with poor-risk rectal cancer defined by MRI can be at high risk of disease recurrence despite standard chemoradiotherapy and optimum surgery. We aimed to assess the safety and long-term efficacy of neoadjuvant chemotherapy with capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision, a treatment strategy developed to enhance the outcome of this population. METHODS: Between November, 2001, and August, 2005, we enrolled eligible patients with poor-risk rectal cancer defined by high-resolution MRI and without metastatic disease. The protocol was amended in January, 2004, following clinically significant cardiotoxic events (nine events in eight of 77 patients), to exclude patients with a recent history of clinically significant cardiac problems. Patients received 12 weeks of neoadjuvant capecitabine and oxaliplatin (oxaliplatin 130 mg/m2 on day 1 with capecitabine 1000 mg/m2 twice daily for 14 days every 3 weeks) followed by chemoradiotherapy (54 Gy over 6 weeks) with capecitabine (825 mg/m2 twice daily), total mesorectal excision, and 12 weeks of postoperative adjuvant capecitabine (1250 mg/m2 twice daily for 14 days every 3 weeks). The primary endpoint was pathological complete response rate. We followed up patients for a median of 55 months (IQR 47-67). Efficacy analyses were undertaken for the intention-to-treat population, unless otherwise specified. This study is registered with ClinicalTrials.gov, number NCT00220051. FINDINGS: 105 eligible patients were enrolled. Radiological response rates after neoadjuvant chemotherapy and chemoradiotherapy were 74% (78/105) and 89% (93/105), respectively. 97 patients underwent surgery, of whom 95 underwent total mesorectal excision, of whom 93 had microscopically clear resection margins and 21 had pathological complete response (21/105 [20%]). 3-year progression-free and overall survival were 68% (95% CI 59-77) and 83% (76-91), respectively. 3-year relapse-free survival for patients who had complete resection was 74% (65-83). Following the protocol amendment for cardiovascular safety, only one further thromboembolic event was reported (fatal pulmonary embolism). INTERPRETATION: Intensification of systemic therapy with neoadjuvant combination chemotherapy before standard treatment is feasible in poor-risk potentially operable rectal cancer, with acceptable safety and promising long-term outcomes. Future development of this multidisciplinary treatment strategy in randomised trials is warranted. FUNDING: UK National Health Service, Sanofi-Aventis.
KeywordsOncology and Carcinogenesis not elsewhere classified; Cancer and Related Disorders
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