Annals of Oncology Advance Access originally published online on January 3, 2006
Annals of Oncology 2006 17(6):1030-1031; doi:10.1093/annonc/mdj119
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© 2005 European Society for Medical Oncology
letter to the editor |
Reply to Letter to the Editor ‘Concurrent oxaliplatin, capecitabine, and radiation therapy in the neoadjuvant therapy of rectal adenocarcinoma: can we get the right dose first?’, by M. G. Fakih (Ann Oncol 2006; 17: 1029)
The phase 1 study of Fakih and colleagues suggests that the recommended doses of capecitabine and oxaliplatin in combination with radiation therapy in the preoperative treatment of rectal cancer should be lower than the ones we used in our phase II study [1
, 2]. In our study, it was pre-planned that the dose of capecitabine could be reduced in the event of 
3 of the first six patients experiencing grade 3/4 diarrhea or febrile neutropenia. No grade 3/4 febrile neutropenia or diarrhea was recorded for these six patients. Among the other grade 3/4 toxicities, we observed only one episode of grade 3 vomiting for these first six patients. Clearly, this unique side effect did not preclude us proceeding with the planned accrual of 40 patients. In our phase II study, diarrhea seemed to occur more frequently than previously described with the other chemoradiation regimens including oxaliplatin (6–33%). Generally, diarrhea was usually easy to manage with dose interruption and, if necessary, dose reduction with rehydration and supportive care as appropriate. Recently, the preliminary results of the Capecitabine Oxaliplatin Radiotherapy and Excision (CORE) were presented [3]. Seventy-three patients were evaluable for toxicity. The most frequent grade 3/4 toxicity was diarrhea occurring in 16% of patients. No other significant toxicity was recorded proving definitively that, for rectal cancer patients, the recommended dosages of oxaliplatin and capecitabine in combination with preoperative radiation therapy (1.8 Gy, 5 days a week over 5 weeks, total dose 45 Gy, 3D conformal technique) are oxaliplatin 50 mg/m2 once weekly for 5 weeks and oral capecitabine 825 mg/m2 twice daily on each day of radiation. The phase 1 trial of Fakih and our study outline that chemoradiation is not always an easy treatment and sometimes could be life threatening. It is possible that the various rate of toxicity reported from one study to another could be explained by a difference in patient selection. In this context, the identification of parameters that will be able to recognize the patients that will experience important side effects is crucial. In our study, the only parameter that correlated significantly with grade 3/4 diarrhea was increasing age (P < 0.01, Figure 1) [2]. In the future, it will be interesting to see if others confirm these results or if new factors predicting toxicity are identified.
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= individual patient of our study;
= deduced probability.Clinique des Pathologies Tumorales du Colon et du Rectum, Centre du Cancer, Université Catholique de Louvain, Brussels, Belgium
* (E-mail: jean-pascal.machiels{at}onco.ucl.ac.be
References
1. Fakih M, Rajput A, Yang G et al. A phase I and biological correlates study of capecitabine (CAP) + oxaliplatin (OX) + radiation therapy in locally advanced rectal cancer (LACR). J Clin Oncol (Annual Meeting Proceedings) 2005; 23: 3633 (Abstr.).
2. Machiels J-P, Duck L, Honhon B et al. Phase II study of preoperative oxaliplatin, capecitabine and external beam radiotherapy with rectal cancer: the RadiOxCape study. Ann Oncol 2005; 16: 1898–1905.
3. Sebag-Montefiore D, Brown G, Rutten H et al. A international phase II study of Capecitabine, Oxaliplatin, Radiotherapy and Excision (CORE) in patients with MRI-defined locally advanced rectal adenocarcinoma, interim results. Eur J Cancer 2005; 3: 170 (Abstr.).
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