Tumori, 97: 280-285, 2011
Concurrent versus sequential administration of CMF chemotherapy and radiotherapy after breast-conserving surgery in early breast cancer Kyubo Kim1, Eui Kyu Chie1, Wonshik Han2, Dong-Young Noh2, Do-Youn Oh3, Seock-Ah Im3, Tae-You Kim3, Yung-Jue Bang3, and Sung W Ha1,4 Departments of 1Radiation Oncology, 2Surgery, and 3Internal Medicine, Seoul National University College of Medicine; 4Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Republic of Korea
ABSTRACT
Aims and background. To compare the outcome of concurrent versus sequential administration of cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) chemotherapy and radiotherapy after breast-conserving surgery in early breast cancer. Methods. From February 1992 to January 2002, 156 patients underwent CMF chemotherapy and radiotherapy, either concurrently (CCRT group, 88 patients) or sequentially (SCRT group, 68 patients). There was a predilection of patients with a larger tumor (P = 0.0035), with more frequent nodal involvement (P = 0.0686), and younger age (P = 0.0776) in the CCRT group. Results. The planned radiotherapy was completed in every patient. No grade 3 or 4 late treatment-related toxicity was observed in the CCRT or SCRT group. Compliance to the treatment as well as cosmetic outcome of the two groups were comparable. Despite more adverse factors for local-regional recurrence in the CCRT group, the 5-year local-regional control rate of the CCRT group was similar to that of the SCRT group (97.7% vs 93.8%, respectively, P = 0.1688). On multivariate analysis, concomitant administration of chemotherapy and radiotherapy was associated with improved localregional control (P = 0.0463). Conclusions. Concurrent administration of CMF chemotherapy and radiotherapy resulted in improved local-regional control over sequential administration without an increase in significant toxicity. Concurrent CMF chemoradiotherapy may serve as a viable option for patients at high-risk of local-regional relapse not suitable for anthracycline or taxane-based chemotherapy.
Introduction Breast conservative therapy comprised of breast-conserving surgery and radiotherapy achieves local control and overall survival comparable with that achieved with mastectomy, and it is considered as a standard treatment in most cases of early breast cancer1. Several trials have attempted to identify a subgroup of patients at low risk of local recurrence where adjuvant radiotherapy would not be necessary2,3. However, results from these studies showed that all patients undergoing breast conservative therapy benefit from radiotherapy. Since patients with risk factors for distant metastases receive chemotherapy4, much attention should be paid to integrating local and systemic treatments. To determine the optimal sequencing of chemotherapy and radiotherapy, several retrospective trials5-7 and a prospective trial8 have been carried out, but most of the studies compared two different types of sequential chemoradiotherapy (SCRT), that is, chemotherapy-first group and radiotherapy-first group.
Key words: breast-conserving surgery, chemotherapy, radiotherapy, sequence. Presented at the 49th Annual Meeting of the American Society for Therapeutic Radiology and Oncology, Los Angeles, CA, Oct 27-Nov 1, 2007. Correspondence to: Eui Kyu Chie, MD, Department of Radiation Oncology, Seoul National University College of Medicine, 101 Daehangno, Jongno-gu, Seoul 110-744, Republic of Korea. Tel +82-2-2072-3705; fax +82-2-765-3317; e-mail
[email protected] Received August 25, 2009; accepted February 16, 2011.
CCRT VS SCRT WITH CMF AFTER BREAST-CONSERVING SURGERY
As an alternative option, concurrent chemoradiotherapy (CCRT) in the adjuvant setting after breast-conserving surgery has been evaluated in several single-arm studies. Of the various chemotherapeutic agents tested, the CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) regimen has been shown to be feasible even at the full dosage9,10. However, the treatment effect of CCRT over SCRT in early breast cancer is still uncertain. Given these observations, a retrospective comparative analysis was done on the outcome of CCRT versus SCRT after breast-conserving surgery for early breast cancer.
Materials and methods Between February 1992 and January 2002, 156 patients underwent CMF chemotherapy and radiotherapy after breast-conserving surgery and axillary lymph node dissection for early stage invasive breast cancer. The median age was 42 years (range, 24-61). All patients had a good performance status, with an ECOG score of 0 or 1. Histologic subtype was invasive ductal carcinoma in 139 patients (89.1%). There were 92 patients (59.0%) with T1, and 64 patients (41.0%) with T2 disease. N stage was retrospectively restaged according to the American Joint Committee for Cancer Staging11. Fifty-six patients (35.9%) had N1 disease, whereas 100 patients (64.1%) were free of nodal metastases. Overall, 54 patients (34.6%) had stage I, 84 patients (53.8%) had stage IIA, and 18 patients (11.5%) had stage IIB disease. Regarding the sequencing of chemotherapy and radiotherapy, there was a trend favoring concomitant CMF chemotherapy and radiotherapy in the early period of the study. This trend was later changed to that favoring upfront CMF chemotherapy followed by radiotherapy. Between the two periods, a “sandwich” regimen was employed. A sandwich treatment schedule comprised three cycles of chemotherapy followed by radiotherapy and an additional three cycles of chemotherapy. Thus, 88 patients received CCRT, 26 patients received a sandwich regimen, and 42 patients received chemotherapy first, followed by radiotherapy. The latter two treatment schedules were grouped into the SCRT arm. The patient, tumor, and treatment characteristics of the two groups are summarized in Table 1. With regard to prognostic factors, there was a predilection of patients with a larger tumor (P = 0.0035), with nodal involvement (P = 0.0686), and younger age (P = 0.0776) in the CCRT group. Median duration of follow-up was 95 months (range, 13-149) for the CCRT group and 69 months (range, 21-153) for the SCRT group. All patients had breast-conserving surgery and axillary lymph node dissection. Most patients underwent R0 resection with clear (145 patients) or close resection margins (2 patients), whereas 4 patients had microscopic residual disease. Information regarding the margin status was unavailable for 5 patients.
281 Table 1 - Patient, tumor and treatment characteristics Variables
No. of pts CCRT
SCRT
P
Age (yr)
