A phase II study of capecitabine plus cisplatin in metastatic triple-negative breast cancer patients pretreated with anthracyclines and taxanes

Abstract

Background: Cisplatin is an effective agent for triple-negative breast cancer (TNBC) and synergistic activity between cisplatin and capecitabine has been demonstrated by in vitro and in vivo studies. This study was designed as a prospective clinical trial to evaluate the efficacy and safety of capecitabine plus cisplatin (XP) regimen in metastatic TNBC patients pretreated with anthracyclines and taxanes. Patients and Methods: Thirty-three patients with metastatic TNBC who had anthracyclines and taxanes as prior therapy were treated with capecitabine 2000 mg/m 2 orally on day 1 through 14 plus cisplatin 75mg/m 2 intravenously on day 1 of a 21-day cycle, followed by capecitabine maintenance medications after a maximum of 6 cycles. The primary end point was objective response rate (ORR) and the secondary end points included progression-free survival (PFS), overall survival (OS) and toxicity profiles. Results: A total of 162 cycles was given. ORR was 63.6%. Median PFS was 8.2 (95%CI: 4.8-11.6) months in the entire population and 10.8 (95%CI: 6.5-15.1) months in responding patients. Median OS was 17.8 (95%CI: 14.4-21.2) months in all enrolled patients and 25.8 (95%CI: 14.6-37.0) months in responding patients. Most adverse events were mild and manageable, with neutropenia and nausea/vomiting as the most common toxicities. Grade 3/4 toxicities included leukopenia (10, 30.3%), neutropenia (10, 30.3%), anemia (2, 6.1%), thrombocytopenia (1, 3.0%), nausea/vomiting (3, 9.1%), hand-foot syndrome (HFS; 1, 3.0%), and sensory neuropathy (1, 3.0%). Conclusions: Capecitabine plus cisplatin demonstrated an excellent activity and an acceptable safety profile in metastatic TNBC patients pretreated with anthracyclines and taxanes.

Capecitabine and cisplatin (XP) combination systemic chemotherapy in heavily pre-treated HER2 negative metastatic breast cancer

“…About 40% of patients received 4 or more lines of systemic chemotherapy prior to XP administration. Although patients were very heavily pre-treated, clinical and survival outcomes were relatively comparable to previous literatures which included cisplatin doublet chemotherapy [ 8 – 10 , 15 , 16 ]. The pathologic subtype, numbers of previous chemotherapy regimen in previous studies were different compared to current study.…”

“…The pathologic subtype, numbers of previous chemotherapy regimen in previous studies were different compared to current study. Li et al [ 8 ] analyzed TNBC patients, and most of the patients received XP as first line for palliative chemotherapy regimen. Other two studies [ 9 , 10 ] comprised breast cancer patients irrespectively to hormone status and HER2 status, and clinical and survival outcomes were relatively comparable to our analysis.…”

“…Combination of cisplatin with 5-FU has shown synergistic effect in prior study [ 7 ], but the clinical effect of cisplatin is not clearly analyzed in breast cancer compared to gastrointestinal cancer. Previous studies have shown the clinical efficacy of capecitabine and cisplatin (XP) combination regimen in unselected MBC patients, but with different patient population and different dosage, schedule of chemotherapeutic agents [ 8 – 10 ]. Considering the toxicity of cisplatin in heavily pretreated patients [ 9 ], there are relatively scarce reports about combining cisplatin to capecitabine.…”

Maintenance chemotherapy after 6 cycles of platinum-doublet regimen in anthracycline-and taxane-pretreated metastatic breast cancer

“…The overall response rate of cisplatin-doublet therapy in our analysis was 37.5% of the prescreened patient population, which was relatively lower than that recently reported in the literature, wherein cisplatin-based chemotherapy was administered at earlier timepoints [4,5,10], but was comparable to that in other reports in which cisplatin was administered in heavily pre-treated MBC patients [6,16]. In our analysis, all patients were anthracycline-and taxane-resistant, and about 40% of the patient population received more than three lines of palliative chemotherapy before enrollment in the study.…”

“…1A). We defined 6 cycles as the timepoint for minimal cisplatin administration, according to previous studies limiting the cisplatin-doublet regimen to up to 6 cycles considering the toxicity associated with cisplatin accumulation [10][11][12]. Patients who received persistent cisplatin-doublet chemotherapy for more than 6 cycles were defined as the doublet-maintenance group.…”