Skip to main content
SpringerLink
Log in

Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

A platinum salt (oxaliplatin or cisplatin) is widely used to enhance chemoradation (CRT) response. The potential of cisplatin in neoadjuvant CRT for locally advanced rectal cancer (LARC) has not been fully investigated. Consecutive patients with histologically confirmed LARC were treated with standard pelvic radiotherapy and concurrent cisplatin plus capecitabine (CisCape CRT). Surgery and eight cycles of adjuvant FOLFOX4 were offered to all patients after CRT. Common biochemical variables and key germline genetic polymorphisms were analyzed as predictors of pathological complete response (pCR). Fifty-one patients were enrolled. pCR (regression AJCC grade 0) was documented in 7 patients (14%), nearly complete response (AJCC grade 1) in 10 pts. There was a strong association between disease-free survival and AJCC grade (p 0.0047). Grade 3–4 toxicities (mainly diarrhea) was observed in 41% of patients. Among all analyzed variables, baseline hemoglobin (Hb) was significantly associated with AJCC grade 0–1 response (p 0.027). As for the pharmacogenetic analysis, XRCC1 rs25487 polymorphism was significantly associated with AJCC grade 0–1, Odds Ratio 25.8, p 0.049. AJCC grade 0–1 response rate for patients with high Hb and/or XRCC1 rs25487 G/G genotype was as high as 57%. Baseline Hb and XRCC1 polymorphisms are valuable selection criteria for the CisCape CRT regimen, given its otherwise meaningful toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Phillips JG, Hong TS, Ryan DP. Multidisciplinary management of early-stage rectal cancer. J Natl Compr Cancer Netw. 2012;10:1577–85.

    Article  CAS  Google Scholar 

  2. Siegel RL, Miller KD, Jemal A. Cancer statistics. CA Cancer J Clin. 2017;67:7–30. https://doi.org/10.3322/caac.21387.

    Article  PubMed  Google Scholar 

  3. Breugom AJ, Swets M, Bosset JF, Collette L, Sainato A, Cionini L, Glynne-Jones R, Counsell N, Bastiaannet E, van den Broek CB, Liefers GJ, Putter H, van de Velde CJ. Adjuvant chemotherapy after preoperative (chemo)radiotherapy and surgery for patients with rectal cancer: a systematic review and meta-analysis of individual patient data. Lancet Oncol. 2015;16:200–7. https://doi.org/10.1016/S1470-2045(14)71199-4.

    Article  PubMed  CAS  Google Scholar 

  4. Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014;15:1245–53. https://doi.org/10.1016/S1470-2045(14)70377-8.

    Article  PubMed  CAS  Google Scholar 

  5. O’Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994;331:502–7.

    Article  PubMed  Google Scholar 

  6. Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, et al. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991;324:709–15.

    Article  PubMed  CAS  Google Scholar 

  7. Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R. German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004;351:1731–40.

    Article  PubMed  CAS  Google Scholar 

  8. Glimelius B, Tiret E, Cervantes A, Arnold D; ESMO Guidelines Working Group. Rectal cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2013;24(Suppl 6):vi81–8. https://doi.org/10.1093/annonc/mdt240.

    Article  Google Scholar 

  9. Trakarnsanga A, Gönen M, Shia J, Nash GM, Temple LK, Guillem JG, Paty PB, Goodman KA, Wu A, Gollub M, Segal N, Saltz L, Garcia-Aguilar J, Weiser MR. Comparison of tumor regression grade systems for locally advanced rectal cancer after multimodality treatment. J Natl Cancer Inst. 2014;106:dju248. https://doi.org/10.1093/jnci/dju248.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Renehan AG, Malcomson L, Emsley R, Gollins S, Maw A, Myint AS, Rooney PS, Susnerwala S, Blower A, Saunders MP, Wilson MS, Scott N, O’Dwyer ST. Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis. Lancet Oncol. 2016;17:174–83. https://doi.org/10.1016/S1470-2045(15)00467-2.

    Article  PubMed  Google Scholar 

  11. Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011;29:2773–80. https://doi.org/10.1200/JCO.2010.34.4911.

    Article  PubMed  CAS  Google Scholar 

  12. O’Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014;32:1927–34. https://doi.org/10.1200/JCO.2013.53.7753.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015;16:979–89. https://doi.org/10.1016/S1470-2045(15)00159-X.

    Article  PubMed  CAS  Google Scholar 

  14. Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2. J Clin Oncol. 2010;28:1638–44. https://doi.org/10.1200/JCO.2009.25.8376.

    Article  PubMed  CAS  Google Scholar 

  15. Schmoll H-J, Haustermans K, Price T. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: disease-free survival results at interim analysis. Proc Am Soc Clin Oncol. 2014;32:3501a.

    Google Scholar 

  16. Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III Trial. J Clin Oncol. 2016;34:3300–7. https://doi.org/10.1200/JCO.2016.66.6198.

    Article  PubMed  CAS  Google Scholar 

  17. Marcu L, van Doorn T, Olver I. Cisplatin and radiotherapy in the treatment of locally advanced head and neck cancer–a review of their cooperation. Acta Oncol. 2003;42:315–25.

    Article  PubMed  CAS  Google Scholar 

  18. Valentini V, Coco C, Cellini N, Picciocchi A, Rosetto ME, Mantini G, Marmiroli L, Barbaro B, Cogliandolo S, Nuzzo G, Tedesco M, Ambesi-Impiombato F, Cosimelli M, Rotman M. Preoperative chemoradiation with cisplatin and 5-fluorouracil for extraperitoneal T3 rectal cancer: acute toxicity, tumor response, sphincter preservation. Int J Radiat Oncol Biol Phys. 1999;45:1175–84.

    Article  PubMed  CAS  Google Scholar 

  19. Glynne-Jones R, Sebag-Montefiore D, Meadows HM, Cunningham D, Begum R, Adab F, Benstead K, Harte RJ, Stewart J, Beare S, Hackshaw A, Kadalayil L; ACT II study group. Best time to assess complete clinical response after chemoradiotherapy in squamous cell carcinoma of the anus (ACT II): a post-hoc analysis of randomised controlled phase 3 trial. Lancet Oncol. 2017;18:347–56. https://doi.org/10.1016/S1470-2045(17)30071-2.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Schrag D, Weiser MR, Goodman KA, et al. Neoadjuvant FOLFOXbev, without radiation, for locally advanced rectal cancer. J Clin Oncol. 2010;28(Suppl):15S.

    Google Scholar 

  21. Winter WE 3rd, Maxwell GL, Tian C, Sobel E, Rose GS, Thomas G, Carlson JW. Association of hemoglobin level with survival in cervical carcinoma patients treated with concurrent cisplatin and radiotherapy: a Gynecologic Oncology Group Study. Gynecol Oncol. 2004;94:495–501.

    Article  PubMed  CAS  Google Scholar 

  22. Abdel-Rahman SZ, El-Zein RA. The 399Gln polymorphism in the DNA repair gene XRCC1 modulates the genotoxic response induced in human lymphocytes by the tobacco-specific nitrosamine NNK. Cancer Lett. 2000;159:63–71.

    Article  PubMed  CAS  Google Scholar 

  23. Matullo G, Palli D, Peluso M, Guarrera S, Carturan S, Celentano E, Krogh V, Munnia A, Tumino R, Polidoro S, Piazza A, Vineis P. XRCC1, XRCC3, XPD gene polymorphisms, smoking and (32)P-DNA adducts in a sample of healthy subjects. Carcinogenesis. 2001;22:1437–45.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Oncology Unit, Department of Systems Medicine, Tor Vergata Clinical Center University Hospital, Tor Vergata University Hospital, Viale Oxford, 81, 00133, Rome, Italy

    Vincenzo Formica, Laura Martano, Ilaria Portarena, Antonella Nardecchia, Jessica Lucchetti, Cristina Morelli & Mario Roselli

  2. Department of Diagnostic Imaging, Molecular Imaging, Interventional Radiology and Radiotherapy, Tor Vergata University Hospital, Rome, Italy

    Michaela Benassi, Emilia Giudice & Riccardo Santoni

  3. Gastrointestinal Unit, Department of Systems Medicine, Tor Vergata University Hospital, Rome, Italy

    Giovanna Del Vecchio Blanco

  4. Anatomic Pathology Institute, Department of Biomedicine and Prevention, Tor Vergata University Hospital, Rome, Italy

    Elena Doldo & Augusto Orlandi

  5. Department of Surgery, Tor Vergata University Hospital, Rome, Italy

    Piero Rossi, Alessandro Anselmo, Pierpaolo Sileri & Giuseppe Sica

Authors
  1. Vincenzo Formica
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michaela Benassi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Giovanna Del Vecchio Blanco
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elena Doldo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laura Martano
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ilaria Portarena
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Antonella Nardecchia
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Jessica Lucchetti
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Cristina Morelli
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Emilia Giudice
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Piero Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Alessandro Anselmo
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Pierpaolo Sileri
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Giuseppe Sica
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Augusto Orlandi
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Riccardo Santoni
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Mario Roselli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Vincenzo Formica.

Ethics declarations

Conflict of interest

All authors disclose no financial and personal relationships with other people or organisations that could inappropriately influence (bias) the present work.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Formica, V., Benassi, M., Del Vecchio Blanco, G. et al. Hemoglobin level and XRCC1 polymorphisms to select patients with locally advanced rectal cancer candidate for neoadjuvant chemoradiotherapy with concurrent capecitabine and a platinum salt. Med Oncol 35, 83 (2018). https://doi.org/10.1007/s12032-018-1141-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-018-1141-4

Keywords

Search

Navigation