Phase II study of capecitabine plus oxaliplatin (CapOX) as adjuvant chemotherapy for locally advanced rectal cancer (CORONA II)

Abstract Objective This multicenter, single-arm phase II study (UMIN000008429) aimed to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapOX) as postoperative adjuvant chemotherapy for patients with locally advanced rectal cancer. Methods Patients with resectable clinical Stage II or III rectal cancer were enrolled to receive eight cycles of CapOX therapy (130 mg/m2 oxaliplatin on day 1 and 2000 mg/m2 oral capecitabine on days 1–14, every 3 weeks) after curative surgical resection. The primary endpoint was 3-year relapse-free survival (RFS) rate, and secondary endpoints were 3-year overall survival (OS) rate, treatment compliance, and safety. Results A total of 40 patients (Stage II, 21; Stage III, 19) were enrolled between September 2012 and November 2015 from seven institutions. Thirty-nine patients (97%) received R0 resection, and 32 patients (84%) received postoperative CapOX therapy. The completion rate of all eight cycles of CapOX therapy was 66%. Relative dose intensities were 87% for oxaliplatin and 84% for capecitabine. At a median follow-up period of 46 months, disease recurrence was observed in nine patients, including three with local recurrence. Three-year RFS and OS rates were 75% (95% CI 57–86%) and 96% (95% CI 80–99%), respectively. Frequencies of Grade ≥ 3 hematological and non-hematologic adverse events were 19% and 38%, respectively. Conclusion CapOX therapy is feasible as adjuvant chemotherapy for locally advanced rectal cancer.

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Phase II study of pre-operative panitumumab and external pelvic radiotherapy (RT) in locally advanced rectal cancer (LARC) patients (pts) (RaP/STAR-03 Study): Preliminary report of safety and treatment compliance.

Journal of Clinical Oncology ◽

10.1200/jco.2015.33.15_suppl.e14502 ◽

2015 ◽

Vol 33 (15_suppl) ◽

pp. e14502-e14502

Author(s):

Carmine Pinto ◽

Francesca Di Fabio ◽

Maurizio DI Bisceglie ◽

Tiziana Pia Latiano ◽

Anna Maria Bochicchio ◽

...

Keyword(s):

Rectal Cancer ◽

Phase Ii ◽

Preliminary Report ◽

Phase Ii Study ◽

Locally Advanced ◽

Treatment Compliance ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Pelvic Radiotherapy

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Phase II study of preoperative bevacizumab, capecitabine, and radiotherapy for resectable locally advanced rectal cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.4_suppl.516 ◽

2011 ◽

Vol 29 (4_suppl) ◽

pp. 516-516 ◽

Cited By ~ 2

Author(s):

M. Martinez Villacampa ◽

C. Santos ◽

M. García ◽

V. Navarro ◽

A. Teule ◽

...

Keyword(s):

Rectal Cancer ◽

Phase Ii ◽

Phase Ii Study ◽

Locally Advanced ◽

Advanced Rectal Cancer ◽

Locally Advanced Rectal Cancer ◽

Sphincter Preservation ◽

R0 Resection ◽

Treatment Schedule ◽

Preoperative Treatment

516 Background: Bevacizumab into chemoradiotherapy appears safe and active in locally advanced rectal cancer (LARC).This study evaluates whether the addition of bevacizumab to capecitabine-based chemoradiotherapy in the preoperative treatment of LARC improves pathological complete response rate (pCR). Methods: Open-label, unicentric, phase II study in patients with resectable LARC (stage II or III), with or without nodal involvement and no evidence of distant metastases. Treatment schedule of 4-cycles: bevacizumab administered iv on day 1 (10 mg/kg in the first cycle and 5 mg/kg in the following 3 cycles) and capecitabine (900mg/m2/bid) in the 2nd cycle (5 d/wk) concomitantly with radiotherapy 45Gy (25 fractions of 1.8Gy/day) over 5 weeks. Surgical resection was scheduled 6-8 weeks after therapy completion. Preliminary results from ITT analysis are presented. Results: Of the 43 patients included, 41 comprised ITT population. Baseline characteristics: median age 63 (55-67) years; male 76%; ECOG 0/1 49%/51%; stage T3/N1 80.5%/58.5%; nodal metastases 85%. 39 patients underwent surgery, 9 abdominoperineal and 30 anterior resection. No evidence of metastasis after surgery in 97%. Total mesorectal excision was performed in 69% of patients and 85% underwent R0 resection. Sphincter-preservation was achieved in 79.5%. Downstaging occurred in 82%. Among 39 patients evaluable for pathological response, 7.7% experienced pCR, 69.2% partial response and 20.5% stable disease. Grade 3/4 toxicities: 9.8% lymphopenia (all related to capecitabine and 4.9% to bevacizumab), 2.4% neutropenia (capecitabine-related), 2.4% radiodermatitis (related to RT and capecitabine) and 2.4% vasospastic angina (bevacizumab and capecitabine-related). 13 patients had postoperative complications not treatment-related. The most common were wound infection (6), intra-abdominal collection (3), wound dehiscence (2) and paralytic ileus (2). Conclusions: Preoperative regimen with bevacizumab, capecitabine and RT is active for LARC with promising results of R0 resection, sphincter- preservation and tumour downstaging as well as manageable toxicity. Further studies are ongoing to confirm these data. No significant financial relationships to disclose.

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Adjuvant chemotherapy with oxaliplatin/5-fluorouracil/leucovorin (FOLFOX) versus 5-fluorouracil/leucovorin (FL) in patients with locally advanced rectal cancer after preoperative chemoradiotherapy followed by surgery: A randomized phase II study (The ADORE).

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.3570 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. 3570-3570 ◽

Cited By ~ 2

Author(s):

Yong Sang Hong ◽

Byung-Ho Nam ◽

Kyung Hae Jung ◽

Jae-Lyun Lee ◽

Kyu-Pyo Kim ◽

...

Keyword(s):

Rectal Cancer ◽

Adjuvant Chemotherapy ◽

Phase Ii ◽

Phase Ii Study ◽

Locally Advanced ◽

Disease Free Survival ◽

Sensory Neuropathy ◽

Advanced Rectal Cancer ◽

Preoperative Chemoradiotherapy ◽

Locally Advanced Rectal Cancer

3570 Background: Preoperative chemoradiotherapy (Pre-CRT) with fluoropyrimidines (Fp) followed by surgery is one of the standard treatments for patients (pts) with locally advanced rectal cancer (LARC); however, the role of adjuvant chemotherapy is still controversial. The aim of this study is to investigate the efficacy of adjuvant FOLFOX for LARC pts who underwent Fp-based Pre-CRT and complete total mesorectal excision (TME). Methods: This randomised phase II study accrued LARC pts whose ypStage was II (ypT3-4/ypN0) or III (any ypT/ypN1-2) after Fp-based Pre-CRT followed by TME. Pts were randomly assigned (1:1) to receive adjuvant chemotherapy either with FL (5-FU 380 mg/m2, leucovorin 20 mg/m2 on D1-5 q 4 weeks X 4 cycles) or FOLFOX (oxaliplatin 85 mg/m2, leucovorin 200 mg/m2 on D1, 5-FU bolus 400 mg/m2 on D1, 5-FU infusion 2400 mg/m2 for 46 hours q 2 weeks X 8 cycles). The primary endpoint was disease-free survival (DFS). Results: A total of 320 pts were randomly assigned (161 FL and 159 FOLFOX) between November 2008 and June 2012, the arms were balanced. By intent-to-treat analysis, estimated 2-year DFS rate was 82.0% in FOLFOX arm and 69.4% in FL arm (HR 0.46 [95% CI, 0.28-0.76], p=0.002) after the median follow-up duration of 22.5 months. The statistical improvements of DFS were maintained regardless of ypStage: 2-year DFS rate was 89.7% (FOLFOX) vs 76.4% (FL) in pts (n=122) with ypStage II (HR 0.32 [0.10-0.98], p=0.035), and 78.1% (FOLFOX) vs 64.4% (FL) in pts (n=198) with ypStage III (HR 0.49, [0.27-0.86], p=0.011). All grade leucopenia (32% vs 22%), neutropenia (70% vs 46%), thrombocytopenia (26% vs 2%) and sensory neuropathy (71% vs5%) were more frequently observed in FOLFOX arm; however, grade 3/4 adverse events (AE) were not different between arms. Conclusions: Adjuvant FOLFOX improved 2-year DFS relative to FL for LARC pts whose ypStage II or III after Fp-based Pre-CRT followed by TME. Significant AEs were not different between arms. The DFS results will be updated in the presentation. Clinical trial information: NCT00807911.

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