Cisplatin given at three divided doses for three consecutive days in metastatic breast cancer: an alternative schedule for one full dose with comparable efficacy but less CINV and hypomagnesaemia.

PURPOSE: Cisplatin, an effective medication for metastatic breast cancer (MBC), is recommended to be applied at the dose of 75 mg/m2 on day 1 every 3 weeks. However, the 75 mg/m2 schedule is often associated with a variety of side effects (such as vomiting and kidney toxicity), and time-consuming hydration treatment is usually needed. Divided dose (25 mg/m2 on day 1-3) without hydration is an alternative. This study aimed to compare the efficacy and toxicity profiles between these two dosage regimens. METHODS: Patients with MBC treated with cisplatin-based regimens in Fudan University Shanghai Cancer Center between December 2008 and June 2019 were retrospectively analyzed. Objective response rate (ORR), progression-free survival (PFS), and toxicity profiles were analyzed. RESULTS: 227 patients receiving a 1-day schedule and 256 patients receiving a 3-day schedule were included. Median PFS was 6.68 (5.66-7.70) months for patients in the 1-day schedule group and 6.70 (5.89-7.52) months for patients in the 3-day schedule group. There was no statistically significant difference in PFS between the two treatment groups (hazard ratio, 0.942; 95% CI 0.759 to 1.170; P = 0.589). The ORRs were comparable between the two groups. ORRs were 44.9% in 1-day schedule group and 44.5% in 3-day schedule group, respectively (P = 0.929). Compared with patients in the 3-day schedule group, patients in the 1-day schedule group experienced higher rates of chemotherapy-induced nausea and vomiting (CINV) (139 [61.2%] vs. 132 [51.6%], P = 0.033). The risk of hypomagnesaemia was also significantly higher (43.2% vs. 28.3%, P = 0.016) among patients receiving 1-day schedule (without magnesium supplementation). No other differences in adverse events were observed between the two groups. CONCLUSIONS: Cisplatin given at three divided doses with no hydration in MBC is a less toxic (less CINV and hypomagnesaemia) schedule with comparable efficacy. Thus, it may be a good alternative for one full-dose (75 mg/m2) schedule.

Intermittent high dose proton pump inhibitor enhances the antitumor effects of chemotherapy in metastatic breast cancer.

BACKGROUND: Acidity is a hallmark of malignant tumor, representing a very efficient mechanism of chemoresistance. Proton pump inhibitors (PPI) at high dosage have been shown to sensitize chemoresistant human tumor cells and tumors to cytotoxic molecules. The aim of this pilot study was to investigate the efficacy of PPI in improving the clinical outcome of docetaxel + cisplatin regimen in patients with metastatic breast cancer (MBC). METHODS: Patients enrolled were randomly assigned to three arms: Arm A, docetaxel 75 mg/m(2) followed by cisplatin 75 mg/m(2) on d4, repeated every 21 days with a maximum of 6 cycles; Arm B, the same chemotherapy preceded by three days esomeprazole (ESOM) 80 mg p.o. bid, beginning on d1 repeated weekly. Weekly intermittent administration of ESOM (3 days on 4 days off) was maintained up to maximum 66 weeks; Arm C, the same as Arm B with the only difference being dose of ESOM at 100 mg p.o. bid. The primary endpoint was response rate. RESULTS: Ninety-four patients were randomly assigned and underwent at least one injection of chemotherapy. Response rates for arm A, B and C were 46.9, 71.0, and 64.5 %, respectively. Median TTP for arm A (n = 32), B (n = 31), C (n = 31) were 8.7, 9.4, and 9.7 months, respectively. A significant difference was observed between patients who had taken PPI and who not with ORR (67.7 % vs. 46.9 %, p = 0.049) and median TTP (9.7 months vs. 8.7 months, p = 0.045) [corrected]. Exploratory analysis showed that among 15 patients with triple negative breast cancer (TNBC), this difference was bigger with median TTP of 10.7 and 5.8 months, respectively (p = 0.011). PPI combination showed a marked effect on OS as well, while with a borderline significance (29.9 vs. 19.2 months, p = 0.090). No additional toxicity was observed with PPI. CONCLUSIONS: The results of this pilot clinical trial showed that intermittent high dose PPI enhance the antitumor effects of chemotherapy in MBC patients without evidence of additional toxicity, which requires urgent validation in a multicenter, randomized, phase III trial. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT01069081 .

Fluoroquinolone resistance in bacteremic and low risk febrile neutropenic patients with cancer.

BACKGROUND: The low risk febrile neutropenic patients with Multinational Association for Supportive Care in Cancer (MASCC) score of more than 20 are recommended to be treated with fluoroquinolone-based oral treatment by the National Comprehensive Cancer Network (NCCN) guideline. This recommendation relies, at least partially, on the high sensitivity of the blood culture isolates to fluoroquinolone in clinical trials conducted in Western countries. Whether this also applies in middle or low income countries like China where antibiotic resistance is becoming prevalent recently has not been evaluated. METHODS: All the positive blood culture results from January 2010 to December 2013 in the 2 large Chinese cancer centers were reviewed. The patients were included into the study with the following criteria: febrile neutropenia, solid tumor or lymphoma, MASCC score >20, positive blood cultures within two days of the onset of fever, and detailed treatment history. RESULTS: A total of 38 patients were included in this analysis. Two patients had polymicrobial bacteremia (Enterococcus faecalis and Flavimonas oryzihabitans). Other isolates included coagulase-negative staphylococcus, micrococcal species, viridans streptococci, Klebsiella pneumoniae, and Escherichia coli. The majority of the monomicrobial isolates from these 36 patients was Escherichia coli (28 patients, 74%). Notably, in contrast to the high sensitivity to fluoroquinolone from blood culture of the low risk patients in previous reports in Westen countries, a very high drug resistance was observed: 13 out of 28 Escherichia coli isolates (46%) or 14 out of all 38 positive cultures (37%). CONCLUSION: The results warrant further validations in prospective clinical trials in countries where antibiotic resistance is prevalent to ensure appropriate antibiotic administration.

Polysaccharide peptide mediates apoptosis by up-regulating p21 gene and down-regulating cyclin D1 gene.

The use of herbal medicine is a common practice among Chinese women with breast cancer. Yunzhi (Voriolus versicolor), a substance that is regarded as a biological response modifier, is frequently used. The aim of the present study is to evaluate the anti-proliferative action of, Yunzhi, polysaccharide peptide (PSP), on breast cancer cells. Breast cancer cells (MDA-MB-231) were cultured with and without PSP for 7 days. Cell growth at 24, 72, 120 and 168 hours was measured by Cell Proliferation Reagent (WST-1). Cells treated with PSP were found to have a significant reduction in cell proliferation as compared to controls after 72 hours of incubation. This lasted for 168 hours. When the effect of PSP on apoptosis was studied by the TdT-mediated X-dUTP nick end-labeling (TUNEL) assay, we found that PSP had a significant effect upon apoptosis from 24 hours onward. Immunostaining showed that PSP increased p21 expression and decreased cyclin D1 expression. In conclusion, PSP is effective in inhibiting cell proliferation through apoptosis. The mechanism for the apoptosis may be through up-regulation of p21 and down-regulation of cyclin D1.