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A phase II study of neoadjuvant bevacizumab plus capecitabine and concomitant radiotherapy in patients with locally advanced rectal cancer

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Abstract

Purpose

To assess safety and activity of neoadjuvant bevacizumab, capecitabine and standard radiotherapy in locally advanced rectal cancer as well as potential predictive biomarkers.

Patients and methods

The multicentric phase II study enrolled 43 patients who received bevacizumab infusion (5 mg/kg) every 2 weeks for 4 cycles; oral capecitabine at 825 mg/m2 twice a day for 5.5 weeks with external–beam irradiation (50.4 Gy in 28 fractions over 5.5 weeks). We determined certain biomarkers before and after therapy for correlation with response.

Results

Post-operative histologic examination revealed no residual cancer cells in 6 of the 43 patients (14%; 95% confidence limits 3.60–24.31%). In another 22 patients (51.2%) a varying percentage of cancer cells in residual areas of fibrosis/ necrosis was found, corresponding to Mandard TRG 2 or 3 classification. Tumor resection with negative circumferential margin was achieved in 38/40 (95%) operated patients. Sphincter–sparing surgery was obtained in 31 (72.1%) patients. Primary tumor and lymph nodes downstaging was observed in 15 (34.9%) and 16 (37.2%) cases, respectively. Neoadjuvant therapy was safe and well tolerated. The most frequent side effects were G1-2 diarrhea, proctitis, rectal bleeding and hypertension. No biomarker tested was significantly predictive of both pathological complete response and disease-free survival. Pre-treatment CD-34 vessel density, post-treatment Ki-67 labeling index and VEGFR-2 cancer cells expression significantly correlated with residual tumor area.

Conclusions

The schedule of neoadjuvant therapy tested was safe and active. Pre-treatment vessel density by the panendothelial marker anti CD-34 antibody, post-treatment Ki-67 labeling index and VEGFR-2 expression were significantly associated to residual tumor area. The biomarkers correlations warrant further evaluation in prospective clinical trials.

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Acknowledgments

The study was supported in part by Roche S.p.A., Italy. We are indebted to the following investigators who participated in the study: Monica Lencioni, Oncologia Medica Ospedale S. Chiara, Pisa; Roberto Murialdo, Dipartimento Medicina Interna Università di Genova; Cristina Granetto, Oncologia Medica, Ospedale S. Croce & Carle, Cuneo; Angelo Martignetti, Dipartimento Oncologia AUSL7, Siena.

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Authors and Affiliations

  1. Unità Operativa Complessa di Oncologia Medica, Azienda Complesso Ospedaliero di Rilevanza Nazionale “S. Filippo Neri”, Via G. Martinotti, 20, 00135, Rome, Italy

    Giampietro Gasparini & Francesco Torino

  2. Graduate School of Medicine, Kyoto University, Kyoto, Japan

    Takayuki Ueno, Junichi Shishido, Yukiko Mori, Satoshi Nagayama & Masakazu Toi

  3. Oncologia Medica Università delle Marche-Ospedale Umberto I, Ancona, Italy

    Stefano Cascinu & Rossana Berardi

  4. Oncologia Medica Università “Federico II”, Napoli, Italy

    Teresa Troiani

  5. Dipartimento Medicina Interna Università di Genova, Genoa, Italy

    Alberto Ballestrero

  6. Department of Laboratory Medicine, Shinshu University Hospital, Nagano, Japan

    Akihiko Yoshizawa

  7. Medical Affairs-Oncology, Roche S.p.A., Milan, Italy

    Paola Morosini

Authors
  1. Giampietro Gasparini
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  2. Francesco Torino
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  3. Takayuki Ueno
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  4. Stefano Cascinu
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  5. Teresa Troiani
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  8. Junichi Shishido
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  9. Akihiko Yoshizawa
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  10. Yukiko Mori
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  11. Satoshi Nagayama
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  12. Paola Morosini
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  13. Masakazu Toi
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Corresponding author

Correspondence to Giampietro Gasparini.

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Gasparini, G., Torino, F., Ueno, T. et al. A phase II study of neoadjuvant bevacizumab plus capecitabine and concomitant radiotherapy in patients with locally advanced rectal cancer. Angiogenesis 15, 141–150 (2012). https://doi.org/10.1007/s10456-011-9250-0

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  • DOI: https://doi.org/10.1007/s10456-011-9250-0

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