Song Santai

Progestin as an alternative treatment option for multi-treated recurrent triple-negative breast cancer

OBJECTIVE Patients with recurrent triple-negative breast cancer (TNBC) currently have no established treatment option other than chemotherapy. However, long-term chemotherapy is often difficult due to adverse effects. A previous study documented a 10%-30% response rate of progestins in oestrogen receptor-negative breast cancer. The aim of this study was to investigate the effect of medroxyprogesterone/megestrol acetate (MPA/MA) in patients with recurrent TNBC. METHODS This retrospective observational analysis included 51 patients with recurrent TNBC; 17 were treated with MPA/MA and 34 underwent chemotherapy. The two groups were matched at a 1:2 ratio according to age, metastatic sites, and salvage treatment lines. Efficacy was compared using the χ2 and rank-sum tests. Progression-free survival (PFS) was calculated using the Kaplan-Meier method, and the two groups were compared using the log-rank test. RESULTS The two groups were well balanced in terms of age, disease-free survival, number of metastases, and salvage therapy lines. Clinical benefit rates in the MPA/MA and chemotherapy groups were 52.94% and 73.53%, respectively (χ2 test, p = 0.208), and median PFS was comparable between groups (log-rank test, p = 0.135). Median PFS of 1st-6th-line salvage treatments was shorter in the MPA/MA group than in the chemotherapy group (log-rank test, p = 0.036), but median PFS of ≥7th-line salvage treatments was comparable (log-rank test, p = 0.139). Eight patients discontinued chemotherapy due to adverse effects, and one patient withdrew from MPA treatment because of weight gain. CONCLUSIONS Progestins (MPA/MA) are an alternative treatment option for multi-treated recurrent TNBC.

Detoxifying effect of Lisheng-Se on CDDP and its relation to metallothionein induction

The effects of Lisheng-Se (Seleninized wheat germ) on metallothionein (MT) induction, lethal systemic toxicity, hemotoxicity and anticancer activity of cisplatin (CDDP), were investigated in mice. The systemic toxicity of CDDP was significantly reduced by preadministration of Lisheng-Se (P<0.05 orP<0.01). The protective effects were better than its inorganic form (Na2 SeO3) and Bi (BSN), (0.05<P<0.1). The MT level in the liver, kidney and tumor tissues of mice treated with one of those compounds was determined. The liver and kidney (P<0.01 andP<0.05). It was just in conformity with the conclusion that the best protective effect appeared in the groups treated with Lisheng-Se. These result suggest that increased MT synthesis in the liver and kidney may be involved in the protective effects of Lashing-Se tested on the lethal toxicity, nephrotoxicity and hemotoxicity produced by CDDP. The experiments also showed that Lisheng-Se did not affect the anticancer activity of CDDPin vitro andin vivo, while the MT level was not increased in cancer (P>0.05), so Lisheng-Se might not only improve the therapeutic index of CDDP, but also did not cause drug-resistance of cancer cells.

Treatment with everolimus for a patient with systemic metastatic breast cancer results in severe pulmonary injury: a case report.

Everolimus has been used in patients with hormone receptor-positive breast cancer. This study reports that treatment with everolimus alone induced severe pulmonary injury in a patient with systemic metastatic breast cancer. A 58-yearold woman with systemic metastatic breast cancer was treated with everolimus alone for 4 weeks and developed severe cough and dyspnea. Computed tomography (CT) scan of the chest showed a progressive lung tumor accompanied by bilateral pulmonary homogeneous ground-glass opacity, especially in the inferior lobe of the left lung. Laboratory examinations revealed a high frequency of monocytes, higher levels of serum alanine aminotransferase (ALT), lactate dehydrogenase (LDH), and C-reactive protein as well as mild hypoxemia and hypocarbia. However, she had no evidence of infection with mycoplasma pneumoniae, chlamydia, pneumocystis, tuberculosis, influenza A virus, and was negative for serum galactomannan (GM) antigen assay. She was suspected to have drug-induced interstitial pneumonia. Everolimus treatment was stopped, and treated with methylprednisolone and empiric antibiotic therapy for 7 days. She received further corticosteroid treatment and felt much better, accompanied by clearance of lung inflammation; she was discharged from hospital. Our experience suggests that treatment with everolimus alone may cause severe pulmonary injury and should be considered carefully in cases of patients with systemic metastatic breast cancer.

Clinical Trial of Letrozole （femara） versus Aminoglutethimide in Postmenopausal Women with Advanced Breast Cancer

AbstractObjective: To compare the response and adverse reactions of aminoglutethimide with that of femara, an oral aromatase inhibitor, in postmenopausal women with advanced breast cancer. Methods: Fifty patients were randomly assigned to femara 2.5 mg once daily (n=26) or aminoglutethimide (n=24) 125 mg twice daily in the first week, 250 mg twice daily in the second week, 250 mg three times daily in the third week and 250 mg four times daily in the fourth week, 30 days for one cycle for both groups. Results: Overall objective response rate (complete+partial) of 26.9% for femara was 12.5% higher than that of aminoglutethimide, but there was no significant difference (P=0.294). The percentages of stable disease were 53.8% and 50.0% respectively in both treatment groups and that of progressive disease of two groups were 19.2% and 37.5%. There was no significant difference between two arms in the receptor status, disease-free intervals, sites of disease and stages of treatment. Femara-related adverse events were fatigue (15.4%), anorexia (11.5%), dizziness (7.7%), nausea (3.8%) and somnolence (3.8%). However, incidence of nausea (25.0%) and vomiting (16.7%) in aminoglutethimide group was obviously higher and severer than that in femara group (P=0.045 and P=0.046). Compared to femara group, frequency in dizziness (25.0%), fatigue (20.8%), anorexia (16.7%), somnolence (12.5%) and cutaneous pruritus (12.5%) was higher in aminoglutethimide group. Allergic rash occurred in aminoglutethimide group. Conclusion: Femara was more effective and well tolerated than aminoglutethimide with respect to side effects in the treatment of postmenopausal women with advanced breast cancer.

Plasma and urinary platinum pharmacokinetics: Relationship to cisplatin nephrotoxicity for patients with breast cancer

Studies were performed in 20 patients with breast cancer, who received 26 cycles of high-dose cisplatin (100 mg/m2, IV. drip). In twenty-five cycles of them urinary Alb, IgG and NAG showed abnormal values. The patients were divided into low-nephrotoxicity and high-nephrotoxicity groups by the degree of renal dysfunction. Thirty-five percent of the patients exhibited high-nephrotoxicity. These patients had significantly higher plasma and/or urinary Pt peak levels during cisplatin (CP) infusion than did low-nephrotoxicity. 70–80% of the patients developed significant nephrotoxicity when urinary Pt peak level rose up to 40 μg/ml or plasma Pt peak level >4 μg/ml. It is quite important to reduce nephrotoxicity that urinary Pt level is controlled below 40 μg/ml and plasma Pt level <4 μg/ml. It is suggested that urine output should be maintained over 300 ml/hr during 2 hours before and after the end of infusion and >100 ml/hr during 3 days after the infusion. That may keep the nephrotoxicity of CP in less serious degree and easy to recover.