Early neutropenia on day 8 treated with adjuvant Docetaxel-based chemotherapy in early breast cancer patients: Putative mechanisms within the neutrophil pool system.

Most chemotherapy regimens cause neutropenic nadirs between days 10 and 14, and administration of granulocyte colony-stimulating factor (G-CSF) support relies on this timing. In docetaxel (DOC)-based chemotherapy, the frequency of febrile neutropenia (FN) and the G-CSF dose administered varied greatly between studies. Our study goal was to forecast the necessary dose of G-CSF by comparing day 8 neutropenia with putative changes within the neutrophil pool. We conducted a retrospective observational analysis of 242 early breast cancer patients who had received adjuvant DOC-based chemotherapy (DOC group) compared with 43 patients who had received FEC chemotherapy (FEC group). Patients who were given a standard dose and had a blood test on day 8 in the 1st cycle were eligible. In the DOC group, patients routinely received prophylactic administration of G-CSF (150 µg/body) on day 3 and received additional G-CSF based on a blood test on day 8. Results of the day 8 blood test showed that severe neutropenia (<500/mm3, average 494/mm3) was observed in 152 out of 242 (62.8%) patients in the DOC group, while in the FEC group (n = 43), neutropenia was ambiguous (average 1,741/mm3). In the FEC group, 9 out of 43 patients (20.9%) and in the DOC group, 27 out of 242 patients (11.1%) experienced FN. In the DOC group, day 8 neutropenia was predictive for FN in a logistic regression model (OR 0.79 [95% CI: 0.655-0.952], p = 0.013). Among 214 patients under 70 years old, the planned chemotherapy cycle was completed in 190 (88.8%) patients who also received the maximum dose of G-CSF (150 µg/body) four times, while 23 patients could not complete the planned chemotherapy cycle, but only five because of FN-related complications. Patients treated with DOC should be treated for primary prophylaxis with G-CSF support at an earlier time starting with a relatively small dose.

Changes in ovarian function in premenopausal women with breast cancer undergoing adjuvant TC (docetaxel and cyclophosphamide) chemotherapy during a brief period of amenorrhea around the last chemotherapy cycle.

PURPOSE: Docetaxel, a chemotherapeutic agent, induces high rates of transient chemotherapy-induced amenorrhea (CIA) when used as adjuvant chemotherapy for premenopausal women with breast cancer. Clinical laboratory data to assess the hormonal environment implicated in inducing transient CIA was assessed. METHODS: An observational study was conducted in 35 premenopausal women with hormone-responsive breast cancer who were receiving adjuvant docetaxel/cyclophosphamide (TC) chemotherapy. Serum estradiol and follicular stimulating hormone (FSH) levels were measured at one (n = 6) or two (n = 29) time point(s) around the completion of chemotherapy. RESULTS: As early as week 6 after the start of chemotherapy, just before the third TC cycle, serum estradiol levels were invariably suppressed (median of 5.5 pg/ml, n = 15, range <5-18.7 pg/ml) and FSH levels increased (median of 63.9 mIU/ml, range 24.5-127.4 mIU/ml), indicative of ovarian suppression to the menopausal levels. Subsequently, at 9 and 12 weeks, serum estradiol levels were suppressed to a median of 6.6 pg/ml (n = 49, range <5-17.3 pg/ml), while FSH levels were high (median of 66.8 mIU/ml, range 29.2-134.5 mIU/ml). There was a significant Spearman's correlation (ρ = 0.95, n = 29, p < 0.01) of high serum FSH levels (24.5-134.5 mIU/ml) between two time points of repeated measurements in 29 patients. TC chemotherapy induced rapid ovarian suppression with the formation of a high and stable plateau in serum FSH levels from week 6 to week 12. CONCLUSIONS: Recovery from transient CIA post-therapy may be partially attributed to high, stable FSH levels that occurred as early as after completion of the second TC chemotherapy cycle.

Low dose capecitabine plus weekly paclitaxel in patients with metastatic breast cancer: a multicenter phase II study KBCSG-0609.

PURPOSE: The combination of capecitabine and paclitaxel (XP) has demonstrated synergistic antitumor activity in preclinical models. The purpose of this phase II study was to evaluate the efficacy and safety of a monthly XP regimen in patients with metastatic breast cancer (MBC). METHODS: Eligible patients had received one or fewer prior chemotherapy regimens for MBC. Patients received oral capecitabine of low dose (828 mg/m(2) twice daily, days 1-21) plus paclitaxel (80 mg/m(2), i.v., over 60 min, days 1, 8 and 15) every 28 days until disease progression or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Progression-free survival (PFS), overall survival (OS) and safety were secondary endpoints. An exploratory analysis of efficacy according to hormone receptor (HR) status was performed. RESULTS: Forty-four patients were enrolled, and 43 patients were evaluable. ORR was 46.5%. PFS and OS were 8.3 and 22.9 months, respectively. ORR was 45.5% in patients with HR-positive tumors and 50% in HR-negative cases. The most frequently observed grade 3/4 adverse events were neutropenia (27.9%), leukopenia (11.6%), hand-foot syndrome (HFS, 9.3%) and fatigue (7.0%). There were no discontinuations due to HFS. CONCLUSIONS: Monthly XP was an effective and well-tolerated regimen for the first- or second-line treatment for MBC.

Down-regulation of HER-2 expression in human breast cancer cell HBC-4 and ZR75-1 by nitrogen-mustard-N-oxide.

BACKGROUND AND AIMS: The human epidermal growth factor receptor type 2 (HER-2) seems to be sensitive to nitrogen mustard, because nitrogen mustard heavily alkylates on guanine. In this study, we examined the effects of nitrogen mustard on cell growth and expression of HER-2 proteins in cultured human breast cancer cells. METHOD: The HER-2 protein levels on the cell surface of breast cancer cells were evaluated following treatment with various concentrations of Nitrogen-mustard-N-oxide using flow cytometry. RESULTS: The HER-2 proteins were detected as high and moderate in ZR75-1 and HBC-4, respectively. The addition of 0.5, 1 and 3 mg/ml of Nitrogen-mustard-N-oxide to the medium significantly decreased in the HER-2 protein with a sharp peak in both the ZR75-1 and HBC-4 cells. The mean value of the HER-2 protein expression in HBC-4 cells was 60%, 51% and 34% of the control, with the growth of 80%, 70% and 50% of the control at 72 hours, respectively. The mean value of HER-2 protein in ZR75-1 cells was 94%, 93% and 70% of the control, with the growth of 70%, 50% and 30% of the control at 72 hours, respectively. A lower dose of Nitrogen-mustard-N-oxide insufficient for growth inhibition did not show a decrease. Only the addition of Nitrogen-mustard-N-oxide in a sufficiently high dose to show growth inhibition down-regulated the HER-2 protein expression in human breast cancer cells. CONCLUSION: We concluded that high concentrations of cyclophosphamide(CPA) might be able to inhibit cell growth through down-regulation of HER-2 protein level in breast cancer cell lines.