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

Abstract

Purpose/Objective(s)After taxane and anthracycline failure, no standard chemotherapy regimen is established in metastatic breast cancer (MBC). Capecitabine and cisplatin (XP) combination shows promising results in gastrointestinal cancer, but there are relatively scarce data in MBC. We reviewed the clinical outcome of XP regimen in anthracycline and taxane resistant, heavily pretreated MBC patients.Materials/MethodsBetween Jan. 2010 to Feb. 2016, 48 HER2 negative MBC patients who failed anthracycline and taxane based chemotherapy were enrolled. In 43.8% of patients, more than 4 regimens were administrated before XP. Thirty-four patients (70.8%) were hormone receptor (HR) positive MBC. Patients were treated with XP (capecitabine [2000mg/m2 per oral; day 1–14] plus cisplatin [60mg/m2 IV; day 1], every 3 weeks) regimen.ResultsMedian progression-free survival (PFS) in total population was 4.33 months (range 1.1~33.57 months). HR positive patients showed trends for superior PFS compared to triple negative breast cancer (TNBC), without statistical significance (6.53 vs. 3.83 months, P = 0.168). In HR positive group, patients receiving 3 or less lines of chemotherapy showed superior PFS compared to others (10.1 vs. 3.0 months, P = 0.039). In multivariate analysis, HR positive patients receiving 3 or less lines of regimens still showed superior PFS (HR = 2.624, 95% CI; 1.071~6.43, P = 0.032). Most common toxicity was grade 3–4 neutropenia, without treatment-related deaths.ConclusionsXP combination regimen showed clinical benefit with tolerable toxicity in heavily pretreated patients, including HR positive patients. After anthracycline and taxane failure, early administration of XP regimen in selected patients may have improve clinical outcome in breast cancer.

Transcriptional Activation of Gstp1 by MEK/ERK Signaling Confers Chemo-Resistance to Cisplatin in Lung Cancer Stem Cells

“…While several studies reported activation of the MEK/ERK cascade in response to cisplatin treatment in several forms of cancer, the consequence of such activation on cell survival remains controversial (26–32). Few studies reported the activation of GST gene expression by MEK/ERK signaling in breast cancer (33–35). Up until the present study, regulation of Gstp1 expression in lung CSCs has not been examined.…”

Differential expression profile analysis of cisplatin‑regulated miRNAs in a human gastric cancer cell line

“…cisplatin is associated with dose-dependent side effects (5,6), including gastrointestinal reactions (7), bone marrow suppression (8), liver and kidney damage (9), ototoxicity (10) and neurotoxicity (11). renal toxicity is frequently encountered, with a clinical incidence rate of 25-35% (12)(13)(14). The side effects associated with cisplatin have limited its use and clinical efficacy (15,16).…”

Cisplatin based therapy: the role of the mitogen activated protein kinase signaling pathway

“…Cisplatin and capecitabine in combination have been demonstrated in gastrointestinal cancers and have shown promising results [ 41 , 42 ]. However, there remains to be limited data on capecitabine in metastatic breast cancers.…”

“…However, there remains to be limited data on capecitabine in metastatic breast cancers. A study carried out by Lee et al [ 41 ], demonstrated capecitabine and cisplatin in combination in anthracycline and taxane resistant, heavily pre-treated HER2 negative metastatic breast cancer, displayed clinical benefit with tolerable toxicity in patients. These findings suggest that the proposed combination may offer an option for patients displaying cancer progression after anthracycline and taxane treatment introduction and also showed promise for HR positive metastatic breast cancer patients.…”