Phase II, Randomized Study of Concomitant Chemoradiotherapy Followed by Surgery and Adjuvant Capecitabine Plus Oxaliplatin (CAPOX) Compared With Induction CAPOX Followed by Concomitant Chemoradiotherapy and Surgery in Magnetic Resonance Imaging–Defined, Locally Advanced Rectal Cancer: Grupo Cáncer de Recto 3 Study

Fernández-Martos, Carlos; Pericay, Carles; Aparicio, Jorge; Salud, Antonieta; Safont, M. J.; Massutí, Bartomeu; Vera, Ruth; Escudero, P.; Maurel, Joan; Marcuello, Eugenio; Mengual, J.; Saigi, E.; Estevan, Rafael; Mira, M.; Polo, Sonia; Hernández, Ana Lluch; Gallén, Manuel; Arias, Fernando; Serra, Javier; Alonso, Vicente

doi:10.1200/jco.2009.25.8541

Cited by 397 publications

(274 citation statements)

References 14 publications

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“…GCR3 was a randomised phase II study of pre-operative OxCap followed by CRT then surgery vs. CRT then surgery then post-operative OxCap in 108 patients. Less toxicity (p=0.0004) and better compliance (p<0.0001) for the same regimen used as NAC compared with AC was demonstrated [49].…”

Section: Rationale For Neoadjuvant Chemotherapy In Rectal Cancermentioning

confidence: 89%

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Gollins

Sebag‐Montefiore

2016

Clinical Oncology

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Improved surgical technique plus selective pre-operative radiotherapy, has decreased rectal cancer pelvic local recurrence (LR) from historically 25%, down to approximately 5-10%. However, this improvement has not reduced distant metastatic relapse, the main cause of death and a key issue in rectal cancer management.The current standard is local pelvic treatment (surgery +/-pre-operative radiotherapy) followed by adjuvant chemotherapy (AC), depending on resection histology. For circumferential resection margin (CRM)-threatened cancer on baseline MRI, downstaging long-course pre-operative chemoradiation (LCPCRT) is generally used. However, for non-CRM threatened disease, varying approaches are currently adopted in the UK, including straight to surgery (STS), short-course pre-operative radiotherapy (SCPRT) and LCPCRT.Clinical trials are investigating intensification of concurrent chemoradiation. There is also increasing interest in investigating pre-operative neoadjuvant chemotherapy (NAC) as a way of exposing micro-metastatic disease to full dose systemic chemotherapy as early as possible and potentially reducing metastatic relapse.Phase II trials suggest that this strategy is feasible, with promising histological response and low rates of tumour progression during NAC. Phase III trials are needed to determine the benefit of NAC when added to standard therapy and also to determine if it can be used instead of neoadjuvant radiotherapy based schedules.

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Section: Rationale For Neoadjuvant Chemotherapy In Rectal Cancermentioning

confidence: 89%

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Gollins

Sebag‐Montefiore

2016

Clinical Oncology

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“…Trials of neoadjuvant infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX) or capecitabine plus oxaliplatin before chemoradiotherapy reported by British and Spanish investigators have demonstrated increased chemotherapy treatment exposure, high response rates, and favorable outcomes. 7,8 On the basis of the results of these trials, as well as our own experiences treating stage IV rectal cancers with FOLFOX, 9 we hypothesized that radiotherapy could be selectively omitted for patients who respond to neoadjuvant FOLFOX and bevacizumab (FOLFOX/ bevacizumab). We were motivated to investigate this strategy both by the possibility of avoiding the toxicities of radiation without compromising local control, and the possibility that earlier introduction of full dose chemotherapy might improve distant control.…”

Section: Journal Of Clinical Oncology O R I G I N a L R E P O R T V Omentioning

confidence: 99%

Neoadjuvant Chemotherapy Without Routine Use of Radiation Therapy for Patients With Locally Advanced Rectal Cancer: A Pilot Trial

Schrag

Weiser

Goodman

et al. 2014

JCO

378

228

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A B S T R A C T PurposeAlthough neoadjuvant chemoradiotherapy achieves low local recurrence rates in clinical stages II to III rectal cancer, it delays administration of optimal chemotherapy. We evaluated preoperative infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX)/bevacizumab with selective rather than consistent use of chemoradiotherapy. Patients and MethodsThirty-two patients with clinical stages II to III rectal cancer participated in this single-center phase II trial. All were candidates for low anterior resection with total mesorectal excision (TME). Patients were to receive six cycles of FOLFOX, with bevacizumab included for cycles 1 to 4. Patients with stable/progressive disease were to have radiation before TME, whereas responders were to have immediate TME. Postoperative radiation was planned if R0 resection was not achieved. Postoperative FOLFOX ϫ 6 was recommended, but adjuvant regimens were left to clinician discretion. The primary outcome was R0 resection rate. ResultsBetween April 2007 and December 2008, 32 (100%) of 32 study participants had R0 resections. Two did not complete preoperative chemotherapy secondary to cardiovascular toxicity. Both had preoperative chemoradiotherapy and then R0 resections. Of 30 patients completing preoperative chemotherapy, all had tumor regression and TME without preoperative chemoradiotherapy. The pathologic complete response rate to chemotherapy alone was 8 of 32 (25%; 95% CI, 11% to 43%). The 4-year local recurrence rate was 0% (95% CI, 0% to 11%); the 4-year disease-free survival was 84% (95% CI, 67% to 94%).

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“…Proven indications exist for the use of intensified chemotherapy as a standard regimen for advanced stage local tumors and expanding tumor growth [12,14,39,40]. The use of an induction chemotherapy followed by standard RCT with 5-FU monotherapy might be more effective concerning tumor response without increasing acute toxicity during RCT [41,42].…”

Section: Discussionmentioning

confidence: 99%

Gender-Specific Acute Organ Toxicity during Intensified Preoperative Radiochemotherapy for Rectal Cancer

et al. 2011

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Learning Objectives After completing this course, the reader will be able to: Describe present strategies of treatment of locally advanced rectal cancer and ongoing clinical trials, including neoadjuvant radiochemotherapy with 50.4 Gy and concomitant 5-FU +/− oxaliplatin.Define the basic clinical parameters, with special emphasis on gender and BMI, correlating with radiochemotherapy-associated side effects in rectal cancer patients and differences in severity of toxicity. CME This article is available for continuing medical education credit at CME.TheOncologist.com Patients with locally advanced rectal cancer (cUICC stages II/III) are typically treated with preoperative 5-fluorouracil–based (5-FU–based) radiochemotherapy (RCT). However, trials are currently being conducted to improve the complete remission rates and the systemic control by combining 5-FU with oxaliplatin. The primary objective was to identify the subgroups of rectal cancer patients who were at risk for high-grade toxicity. All 196 patients who were included in the present study were treated with 50.4 Gy and chemotherapy that included either 5-FU (n = 115) or 5-FU+oxaliplatin (n = 81). The preoperative RCT was followed by a total mesorectal excision and adjuvant chemotherapy. Acute toxicity was monitored weekly and a toxicity grade ≥3 (Common Toxicity Criteria) for a skin reaction, cystitis, proctitis, or enteritis was defined as high-grade acute organ toxicity. After RCT with 5-FU+oxaliplatin, complete tumor remission was achieved in 13.6% of the patients and in 11.3% after RCT with 5-FU alone. Complete irradiation dosages of 50.4 Gy were given to 99% (5-FU) and 95% (5-FU+oxaliplatin) of the patients. Concomitant chemotherapy was fully administered in 95% of the patients treated with 5-FU compared with the 84% of patients treated with 5-FU+oxaliplatin. A significantly higher proportion of acute organ toxicity was found in the patients who were treated with 5-FU+oxaliplatin compared with those who were treated with 5-FU. Additionally, women with a low body mass index were at the highest risk for acute organ toxicity. These results suggest that there are basic clinical parameters, such as gender and body mass index, that may be potential markers for generating individual risk profiles of RCT-induced toxicity.

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Cited by 397 publications

References 14 publications

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Neoadjuvant Treatment Strategies for Locally Advanced Rectal Cancer

Neoadjuvant Chemotherapy Without Routine Use of Radiation Therapy for Patients With Locally Advanced Rectal Cancer: A Pilot Trial

Gender-Specific Acute Organ Toxicity during Intensified Preoperative Radiochemotherapy for Rectal Cancer

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