title: Neoadjuvant sandwich treatment with oxaliplatin and capecitabine administered prior to, concurrently with, and following radiation therapy in locally advanced rectal cancer: a prospective phase 2 trial.
abstract: OBJECTIVE
  Systemic failure remains the major challenge in management of locally advanced rectal cancer (LARC). To optimize the timing of neoadjuvant treatment and enhance systemic control, we initiated a phase 2 trial to evaluate a new strategy of neoadjuvant sandwich treatment, integrating induction chemotherapy, concurrent chemoradiation therapy, and consolidation chemotherapy. Here, we present preliminary results of this trial, reporting the tumor response, toxicities, and surgical complications.
  
  
  METHODS
  Fifty-one patients with LARC were enrolled, among which were two patients who were ineligible because of distant metastases before treatment. Patients were treated first with one cycle of induction chemotherapy consisting of oxaliplatin, 130 mg/m² on day 1, with capecitabine, 1000 mg/m² twice daily for 14 days every 3 weeks (the XELOX regimen), followed by chemoradiation therapy, 50 Gy over 5 weeks, with the modified XELOX regimen (oxaliplatin 100 mg/m²), and then with another cycle of consolidation chemotherapy with the XELOX regimen. Surgery was performed 6 to 8 weeks after completion of radiation therapy. Tumor responses, toxicities, and surgical complications were recorded.
  
  
  RESULTS
  All but one patent completed the planned schedule of neoadjuvant sandwich treatment. Neither life-threatening blood count decrease nor febrile neutropenia were observed. Forty-five patents underwent optimal surgery with total mesorectal excision (TME). Four patients refused surgery because of clinically complete response. There was no perioperative mortality in this cohort. Five patients (11.1%) developed postoperative complications. Among the 45 patients who underwent TME, pathologic complete response (pCR), pCR or major regression, and at least moderate regression were achieved in 19 (42.2%), 37 (82.2%), and 44 patients (97.8%), respectively.
  
  
  CONCLUSIONS
  Preliminary results suggest that the strategy of neoadjuvant sandwich treatment using XELOX regimen as induction, concomitant, and consolidation chemotherapy to the conventional radiation is well tolerated. The strategy is highly effective in terms of pCR and major regression, which warrants further investigation.
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Yuan-Hong
authors.initials: YH
authors.lastname: Gao
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Jun-Zhong
authors.initials: JZ
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: An
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Jie-Lin
authors.initials: JL
authors.lastname: Luo
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Mu-Yan
authors.initials: MY
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Pei-Qiang
authors.initials: PQ
authors.lastname: Cai
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Ling-Heng
authors.initials: LH
authors.lastname: Kong
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Guo-Chen
authors.initials: GC
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Jing-Hua
authors.initials: JH
authors.lastname: Tang
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China.
authors.forename: Zhi-Zhong
authors.initials: ZZ
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, PR China; Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, PR China. Electronic address: dingpr@mail.sysu.edu.cn.
authors.forename: Pei-Rong
authors.initials: PR
authors.lastname: Ding
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods; D060830:Consolidation Chemotherapy / Q000009:adverse effects / Q000379:methods*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005240:Feasibility Studies; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D060828:Induction Chemotherapy / Q000009:adverse effects / Q000379:methods*; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy / Q000009:adverse effects / Q000379:methods*; D010071:Oxaloacetates; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery
chemical_list: D010071:Oxaloacetates; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil