Annals of Oncology Advance Access originally published online on August 3, 2005
Annals of Oncology 2005 16(9):1559-1560; doi:10.1093/annonc/mdi287
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© 2005 European Society for Medical Oncology
Letter to the Editor |
In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer
In the January issue of Annals of Oncology, von Minckwitz and colleagues reported their pilot study of preoperative chemotherapy with the TAC regimen (docetaxel, adriamycin, and cyclophosphamide) adapted by clinical evaluation after two cycles [1
]. The patients with at least partial response received four additional cycles of TAC although the others were randomised to either TAC or the combination of vinorelbine and capecitabine (NX). A high complete pathological response rate (pCR) of 22.9% was obtained in responders to the first two cycles. Nevertheless, this study deserves a number of additional comments. The first point is the method of evaluation of response since there is also a demonstration of the poor correlation between palpation and echography. A second point is the recruitment which did not favour chemosensitivity given the minority of patients (36%) with histologic grade III, or with hormone negative status (32%). More than 25% of the patients were older than 60 years who would probably have poorly tolerated such a heavy regimen. We do not agree with the relatively optimistic presentation of the toxicity which included febrile neutropenia in 13.5% of the patients under TAC and grade III/IV neutropenia in 34% under NX. It must be taken into account that the patients have been particularly well followed in the setting of a clinical trial conducted in university hospitals. Moreover, the patients have been inevitably selected. These phenomenon are particularly well illustrated by the extremely low rate of manageable toxicity such as nausea, edema, or hand-foot syndrome. The administration of TAC or NX might be more problematic in general practice. Regarding the results, the low pCR after NX indicates the inefficacy of this regimen after failure of TAC, which is conceptually comprehensible and should lead to its disqualification. In fact, the key-point is the choice of TAC since a high proportion of the tumours is resistant to at least one of the three drugs while all patients are exposed to toxicity. There is a contradiction between in vivo adaptation and the use of a wide-spectrum regimen with no possibility of second-line therapy. In the Aberdeen study, the patients who were refractory to the anthracyclin-based regimen exceptionally took benefit from docetaxel [2]. In fact, all these studies indicates that there is a fraction of clearly refractory patients. Even an intensified regimen did not show improvement in the results. In a study of 57 patients with stage III disease receiving three cycles of epirubicin, 100 mg/m2, and cyclophosphamide, 1200 mg/m2 every two weeks, the pCR was only 3.5% [3]. A phase III study comparing EC (epirubicin, 120 mg/m2 and cyclophosphamide, 830 mg/m2 every 2 weeks) with FEC (5-fluorouracil, epirubicin, 60 mg/m2 D1, and cyclophosphamide, 75 mg/m2/day D1-D14, one cycle every 4 weeks), resulted in equivalent pCR [4]. In conclusion, a sequential treatment including a taxane in responders seems an appropriate approach in hormone negative receptor patients with probably no loss of chance but less toxicity. Unfortunately, no alternative approach is proposed to the other patients while hormonal therapy, trastuzumab, or even irradiation might be considered.
Hematology/Oncology Division, General Hospital of Annemasse, France
(Email: alliotcfr{at}yahoo.fr)
References
1. von Minckwitz G, Blohmer JU, Raab G et al. In vivo chemosensitivity-adapted preoperative chemotherapy in patients with early-stage breast cancer: the GERPATRIO pilot study. Ann Oncol 2005; 16: 56–63.
2. Smith IC, Heys SD, Hutcheon AW et al. Neoadjuvant chemotherapy in breast cancer: significantly enhanced response with docetaxel. J Clin Oncol 2002; 20: 1456–1466.
3. Fisher B, Anderson S, DeCillis A et al. Further evaluation of intensified and increased total dose of cyclophosphamide for the treatment of primary breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-25. J Clin Oncol 1998; 17: 3374–3388.
4. Therasse P, Mauriac L, Welnicka-Jasliewicz M et al. Final results of a randomized phase III study comparing cyclophosphamide, epirubicin, and fluorouracil with a dose intensified epirubicin and cyclophosphamide + filgrastim as neo-adjuvant treatment in locally advanced breast cancer: an EORTC-NCIC-SAKK multicenter study. J Clin Oncol 2003; 21: 843–850.
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