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Phase I trial of neoadjuvant chemoradiotherapy (CRT) with capecitabine and weekly irinotecan followed by laparoscopic total mesorectal excision (LTME) in rectal cancer patients

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Summary

Background: To analyze the feasibility of capecitabine with weekly irinotecan and concurrent radiotherapy followed by laparoscopic-total mesorectal excision (LTME) in rectal cancer patients. Methods: Eligible criteria included adenocarcinoma of the rectum staged by endoscopic ultrasonography (u), spiral abdominal and pelvic CT and chest X-ray. Patients received weekly irinotecan 50 mg/m2 (days 1, 8, 15, 22, 29) and capecitabine (days 1 through 5 for 5 weeks); dose level; (DL) I 250 mg/m2/bid; DL II 375 mg/m2/bid; DL III 500 mg/m2/bid, according to phase I methodology. External beam radiotherapy was delivered up to a total dose of 45 Gy in daily fractions of 1.8 Gy, 5 days a week. LTME was planned 5–7 weeks after CRT. Results: From February 2003 to February 2006, 22 patients were included. Median age was 62 (range 48 to 78). Seven pts were uT3N0 and 15 pts uT3N1. Seven patients were treated at DL I, six at DL II and nine at DL III. Grade 3 adverse events were observed in all levels. The maximum tolerated dose was reached at 375 mg/m2 (DL II). Conversion rate to open surgery was 5%. Median hospital stay was 6.6 days. One month post-surgical complications were noted in five patients (23%). Median excised nodes were 11 (range 4–21). Pathological complete response was observed in two patients (9%). Conclusions: LTME after preoperative CRT with CAPIRI is feasible but severe adverse events were found in all levels despite the use of lower dose of capecitabine than previously published.

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Authors’ Disclosures of potential conflicts of interest

The authors declare no potential conflicts of interest.

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Authors and Affiliations

  1. Medical Oncology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Catalonia, Spain

    Lisardo Ugidos, Rosa Gallego, Monica Tosca & Joan Maurel

  2. Gastrointestinal Surgery Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Catalonia, Spain

    Salvadora Delgado & Antonio de Lacy

  3. Radiation Oncology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Catalonia, Spain

    Carlos Conill

  4. Gastrointestinal Surgery Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Catalonia, Spain

    Carlos Conill

  5. Gastroenterology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Catalonia, Spain

    Angels Ginés & Antoni Castells

  6. Radiology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Catalonia, Spain

    Juan Ramón Ayuso

  7. Pathology Department, Hospital Clínic Barcelona, Institut d’Investigacions Biomèdiques August Pi I Sunyer (IDIBAPS), CIBERehd, University of Barcelona, Catalonia, Spain

    Rosa Miquel

  8. Medical Oncology Department, Institut Clínic de Malalties Hemato-Oncológiques, Hospital Clínic, Villarroel 170, 08036, Barcelona, Spain

    Joan Maurel

Authors
  1. Lisardo Ugidos
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  2. Salvadora Delgado
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  3. Carlos Conill
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  4. Angels Ginés
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  5. Rosa Gallego
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  6. Juan Ramón Ayuso
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  7. Rosa Miquel
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  8. Monica Tosca
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  9. Antonio de Lacy
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  10. Antoni Castells
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  11. Joan Maurel
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Correspondence to Joan Maurel.

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Ugidos, L., Delgado, S., Conill, C. et al. Phase I trial of neoadjuvant chemoradiotherapy (CRT) with capecitabine and weekly irinotecan followed by laparoscopic total mesorectal excision (LTME) in rectal cancer patients. Invest New Drugs 27, 262–268 (2009). https://doi.org/10.1007/s10637-008-9192-6

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  • DOI: https://doi.org/10.1007/s10637-008-9192-6

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