title: CAPIRI-IMRT: a phase II study of concurrent capecitabine and irinotecan with intensity-modulated radiation therapy for the treatment of recurrent rectal cancer.
abstract: BACKGROUND
  This study investigated the local effect and acute toxicity of irinotecan and capecitabine with concurrent intensity-modulated radiation therapy (IMRT) for the treatment of recurrent rectal cancer without prior pelvic irradiation.
  
  
  METHODS
  Seventy-one patients diagnosed with recurrent rectal cancer who did not previously receive pelvic irradiation were treated in our hospital from October 2009 to July 2012. Radiotherapy was delivered to the pelvis, and IMRT of 45 Gy (1.8 Gy per fraction), followed by a boost of 10 Gy to 16 Gy (2 Gy per fraction), was delivered to the recurrent sites. The concurrent chemotherapy regimen was 50 mg/m(2) irinotecan weekly and 625 mg/m(2) capecitabine twice daily (Mon-Fri). Radical surgery was recommended for medically fit patients without extra-pelvic metastases. The patients were followed up every 3 months. Tumor response was evaluated using CT/MRIs according to the RECIST criteria or postoperative pathological findings. NCI-CTC 3.0 was used to score the toxicities.
  
  
  RESULTS
  Forty-eight patients (67.6%) had confirmed recurrent rectal cancer without extra pelvic metastases, and 23 patients (32.4%) had extra pelvic metastases. Fourteen patients (19.7%) underwent radical resections (R0) post-chemoradiation. A pathologic complete response was observed in 7 of 14 patients. A clinical complete response was observed in 4 patients (5.6%), and a partial response was observed in 22 patients (31.0%). Only 5 patients (7.0%) showed progressive disease during or shortly after treatment. Of 53 symptomatic patients, clinical complete and partial symptom relief with chemoradiation was achieved in 56.6% and 32.1% of patients, respectively. Only 2 patients (2.8%) experienced grade 4 leukopenia. The most common grade 3 toxicity was diarrhea (16 [22.5%] patients). The median follow-up was 31 months. The cumulative local progression-free survival rate was 74.2% and 33.9% at 1 and 3 years after chemoradiation, respectively. The cumulative total survival rate was 80.1% and 36.5% at 1 and 3 years after chemoradiation, respectively.
  
  
  CONCLUSIONS
  This study revealed that concurrent irinotecan and capecitabine with IMRT significantly relieves local symptoms and exhibits promising efficacy with manageable toxicities in recurrent rectal cancer without prior pelvic irradiation. Improving the rate of R0 resections will be investigated in a future study.
authors.affiliation: Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China. caigangcg@163.com.
authors.forename: Gang
authors.initials: G
authors.lastname: Cai
authors.affiliation: Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China. leo.zhu@126.com.
authors.forename: Ji
authors.initials: J
authors.lastname: Zhu
authors.affiliation: Department of Radiation Oncology, Kimmel Cancer Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA, USA. Joshua.palmer@jeffersonhospital.org.
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Palmer
authors.affiliation: Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China. xu.shirley021@gmail.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China. jackhuwg@gmail.com.
authors.forename: Weigang
authors.initials: W
authors.lastname: Hu
authors.affiliation: Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China. guweilie@hotmail.com.
authors.forename: Weilie
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China. drsanjuncai@163.com.
authors.forename: Sanjun
authors.initials: S
authors.lastname: Cai
authors.affiliation: Department of Radiation Oncology, Shanghai Cancer Center, Shanghai Medical College, Fudan University, 270 Dong An Road, Shanghai, China. zhenzhang6@yahoo.com.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D000069287:Capecitabine / Q000008:administration & dosage; D059248:Chemoradiotherapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D009367:Neoplasm Staging; D010386:Pelvic Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D011379:Prognosis; D011446:Prospective Studies; D050397:Radiotherapy, Intensity-Modulated; D012004:Rectal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D012074:Remission Induction; D015996:Survival Rate; D055815:Young Adult
chemical_list: D000069287:Capecitabine; D000077146:Irinotecan; D002166:Camptothecin