Abstract
Introduction
A prospective phase II study was conducted to assess the clinical activity and tolerability of oxaliplatin, capecitabine, and radiotherapy (RT) for neoadjuvant therapy of stages II–III rectal cancer.
Materials and methods
Patients with histologically confirmed stages II–III (T3–T4 and/or N+) resectable rectal adenocarcinoma were eligible. Capecitabine was administered at 825 mg/m2 twice daily for 5 days/week and oxaliplatin at 50 mg/m2 on day 1 weekly for 5 weeks starting the first day of RT (before RT). RT consisted of a total dose of 45 Gy delivered in 25 fractions of 1.8 Gy, 5 days per week, for 5 weeks.
Results
A total of 46 patients were included (35 male, 10 female, median age 62 years). TNM Stage was T3 in 43 patients and T4 in 2. Twenty-eight patients had suspected nodal involvement. The intended chemoradiation treatment was completed in 94 % patients. Grade 3/4 toxicity included lymphocytopenia (6 patients), diarrhea (4 patients), emesis (2 patients), asthenia (3 patients), anorexia (1 patient), and hepatic toxicity (1 patient). Grade 1 neurotoxicity occurred in 18 patients, Grade 2 neurotoxicity in 3, and Grade 1 palmoplantar erythrodysesthesia in 2. Forty-two patients underwent surgery (complete resection 95 %, sphincter-saving operation 55 %). The overall pathologic response rate was 83 %, with a pathologic complete response (pCR) rate of 11.9 % (95 % CI 4.0–25.6).
Conclusions
The pCR rate observed with oxaliplatin plus capecitabine and RT did not reach the pre-specified criteria of efficacy in this trial, which is in line with recent results of randomized phase III trials.
Similar content being viewed by others
References
Sauer R, Becker H, Hohenberger W et al (2004) Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med 351:1731–1740
Bosset JF, Collette L, Calais G et al (2006) Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med 355:1114–1123
Gérard JP, Conroy T, Bonnetain F et al (2006) Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3–4 rectal cancers: results of FFCD 9203. J Clin Oncol 24:4620–4625
Pasetto LM, Pucciarelli S, Agostini M, Rossi E, Monfardini S (2004) Neoadjuvant treatment for locally advanced rectal carcinoma. Crit Rev Oncol Hematol 52:61–71
Smalley SR, Benedetti JK, Williamson SK et al (2006) Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol 24:3542–3547
Yerushalmi R, Idelevich E, Dror Y et al (2006) Preoperative chemoradiation in rectal cancer: retrospective comparison between capecitabine and continuous infusion of 5-fluorouracil. J Surg Oncol 93:529–533
De Paoli A, Chiara S, Luppi G et al (2006) Capecitabine in combination with preoperative radiation therapy in locally advanced, resectable, rectal cancer: a multicentric phase II study. Ann Oncol 17:246–251
Desai SP, El-Rayes BF, Ben-Josef E et al (2007) A phase II study of preoperative capecitabine and radiation therapy in patients with rectal cancer. Am J Clin Oncol 30:340–345
Cassidy J, Tabernero J, Twelves C et al (2004) XELOX (capecitabine plus oxaliplatin): active first-line therapy for patients with metastatic colorectal cancer. J Clin Oncol 22:2084–2091
Díaz-Rubio E, Tabernero J, Gómez-España A et al (2007) Phase III study of capecitabine plus oxaliplatin compared with continuous-infusion fluorouracil plus oxaliplatin as first-line therapy in metastatic colorectal cancer: final report of the Spanish Cooperative Group for the Treatment of Digestive Tumors Trial. J Clin Oncol 25:4224–4230
Maindrault-Goebel F, de Gramont A, Louvet C et al (2001) High-dose intensity oxaliplatin added to the simplified bimonthly leucovorin and 5-fluorouracil regimen as second-line therapy for metastatic colorectal cancer (FOLFOX 7). Eur J Cancer 37:1000–1005
Willeke F, Horisberger K, Kraus-Tiefenbacher U et al (2007) A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer. Br J Cancer 96:912–917
Corvò R, Pastrone I, Scolaro T et al (2003) Radiotherapy and oral capecitabine in the preoperative treatment of patients with rectal cancer: rationale, preliminary results and perspectives. Tumori 89:361–367
Glynne-Jones R, Sebag-Montefiore D, Maughan TS, Falk SJ, McDonald AC (2006) A phase I dose escalation study of continuous oral capecitabine in combination with oxaliplatin and pelvic radiation (XELOC-RT) in patients with locally advanced rectal cancer. Ann Oncol 17:50–56
Koeberle D, Burkhard R, von Moos R et al (2008) Phase II study of capecitabine and oxaliplatin given prior to and concurrently with preoperative pelvic radiotherapy in patients with locally advanced rectal cancer. Br J Cancer 98:1204–1209
Navarro M, Dotor E, Rivera F et al (2006) A phase II study of preoperative radiotherapy and concomitant weekly irinotecan in combination with protracted venous infusion 5-fluorouracil, for resectable locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 66:201–205
Aristu JJ, Arbea L, Rodriguez J et al (2008) Phase-II trial of concurrent capecitabine and oxaliplatin with preoperative intensity-modulated radiotherapy in patients with locally advanced rectal cancer. Int J Radiat Oncol Biol Phys 71:748–755
Hospers GA, Punt CJ, Tesslaar ME et al (2007) Preoperative chemoradiotherapy with capecitabine and oxaliplatin in locally advanced rectal cancer. A phase I–II multicenter study of the Dutch Colorectal Cancer Group. Ann Surg Oncol 14:2773–2779
Fakih M, Bullarddunn K, Yang GY (2008) Phase II study of weekly intravenous oxaliplatin combined with oral daily capecitabine and radiotherapy with biologic correlates in neoadjuvant treatment of rectal adenocarcinoma. Int J Radiat Oncol Biol Phys 72:650–657
Heudel P, Romestaing P, Barbet N et al (2008) Capecitabine, irinotecan, oxaliplatin (CAPIRINOX) and concomitant irradiation in advanced rectal cancer: the Lyon R-02-01 Phase I Trial. Clin Oncol 20:369–374
Klautke G, Fietkau R (2007) Intensified neoadjuvant radiochemotherapy for locally advanced rectal cancer: a review. Int J Colorectal Dis 22:457–465
Cancer Therapy Evaluation Program. Common toxicity criteria, version 2.0, 1998. http://ctep.cancer.gov/reporting/ctc.html
Simon R (1989) Optimal two-stage designs for phase II clinical trials. Control Clin Trials 10:1–10
Weiser MR (2011) Rectal cancer trials: no movement. J Clin Oncol 29:2746–2748
Hoffe SE, Shridhar R, Biagioli MC (2010) Radiation therapy for rectal cancer: current status and future directions. Cancer Control 17:25–34
Machiels JP, Duck L, Honhon B et al (2005) Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy in patients with rectal cancer: the RadiOxCape study. Ann Oncol 16:1898–1905
Chau I, Brown G, Cunningham D et al (2006) Neoadjuvant capecitabine and oxaliplatin followed by synchronous chemoradiation and total mesorectal excision in magnetic resonance imaging-defined poor-risk rectal cancer. J Clin Oncol 24:668–674
Rödel C, Liersch T, Hermann RM et al (2007) Multicenter phase II trial of chemoradiation with oxaliplatin for rectal cancer. J Clin Oncol 25:110–117
Gérard JP, Azria D, Gourgou-Bourgade S et al (2010) 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 28:1638–1644
Aschele C, Cionini L, Lonardi S et al (2011) Primary tumor response to preoperative chemoradiation with and without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol 29:2773–2780
Roh MS, Yothers GA, O’Connell MJ et al (2011) The impact of capecitabine and oxaliplatin in the preoperative multimodality treatment in patients with carcinoma of the rectum: NSABP R-04. J Clin Oncol 29(suppl; abstr 3503)
Roedel C, Becker H, Fietkau R et al (2011) Preoperative chemoradiotherapy and postoperative chemotherapy with 5-fluorouracil and oxaliplatin versus 5-fluorouracil alone in locally advanced rectal cancer: First results of the German CAO/ARO/AIO-04 randomized phase III trial. J Clin Oncol 29(suppl; abstr LBA3505)
Acknowledgments
We thank the patients and the medical and nursing staff of all the participating institutions, Inma Ruiz de Mena from the Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD) for logistic support, AAIPharma for monitoring, statistics and data management. The study was supported by an unrestricted grant from Roche and Sanofi Aventis, Spain.
Conflict of interest
Margarita Majem, Matilde Navarro, Ferran Losa, Vicente Alonso, Manel Gallén, Pilar Escudero, Encarnación González, have no potential conflicts of interest. Consultant or advisory role: Ramon Salazar, Roche: Bartomeu Massutí, Roche; Enrique Aranda, Roche; Fernando Rivera, Roche and Sanofi Aventis. Travel and Research Grants: Fernando Rivera, Roche and Sanofi Aventis. Honoraria: Bartomeu Massutí, Roche; Manuel Benavides; Sanofi Aventis.
Author information
Authors and Affiliations
Corresponding author
Additional information
On behalf of the Spanish Cooperative Group for Digestive Tumor Therapy (TTD).
Rights and permissions
About this article
Cite this article
Salazar, R., Navarro, M., Losa, F. et al. Phase II study of preoperative radiotherapy and concomitant weekly intravenous oxaliplatin combined with oral capecitabine for stages II–III rectal cancer. Clin Transl Oncol 14, 592–598 (2012). https://doi.org/10.1007/s12094-012-0846-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12094-012-0846-7