Long-term renal safety profile of ibandronate 6 mg infused over 15 minutes.

BACKGROUND: In an earlier study, intravenous (i.v.) ibandronate 6 mg administered every 3-4 weeks had a similarly good renal safety profile whether infused over 15 or 60 min in women with breast cancer and bone metastases. This current study focuses on the renal safety of the extended use of ibandronate. PATIENTS AND METHODS: Patients completing the original study could choose to enter a follow-up phase and continue (or switch) to receive ibandronate 6 mg by 15-min i.v. infusion every 3-4 weeks. The primary endpoint was the percentage of patients with a serum creatinine increase of ≥44.2 mmol/l (= 0.5 mg/dl) from core baseline. RESULTS: Fourteen patients entered the follow-up phase and received a median of 16 infusions (range: 9-24). No patient reached the primary endpoint. Most adverse events were mild to moderate in intensity. None of the 6 reported treatment-related adverse events was considered severe or reported as a serious adverse event. CONCLUSIONS: Ibandronate was well tolerated when administered as a 6-mg i.v. infusion over 15 min every 3-4 weeks during the follow-up phase to the earlier core study. No evidence of any treatment-related deterioration in renal function was noted, and no new or unexpected adverse events occurred.

The effect of loss of Brca1 on the sensitivity to anticancer agents in p53-deficient cells.

BRCA1 is implicated in cellular responses to DNA damage, thereby substantially contributing to maintenance of the genome integrity. Mutations in the BRCA1 gene occur in breast and ovarian cancer and mutations that disable p53 are frequently found in human cancers, often accompanied by mutations in additional genes, contributing to tumor progression or high-grade malignancy. Therefore, the role of BRCA1 in the sensitivity to anticancer agents in p53-deficient cells was investigated using p53-deficient mouse knockout cell lines either deficient or proficient in Brca1 function. We report that Brca1-deficiency in p53-null cells was associated with increased sensitivity to the topoisomerase I poisons camptothecin and topotecan, the topoisomerase II poisons doxorubicin, mitoxantrone and etoposide, and to the platinum compounds carboplatin and oxaliplatin, but not to the antimetabolites 5-fluorouracil and gemcitabine and the taxanes docetaxel and paclitaxel. The increased growth inhibition to doxorubicin after loss of Brca1 correlated with increased cell killing caused by increased apoptosis. The data presented here indicate that Brca1 modulates p53-independent DNA damage response pathways and they support the case of a role of Brca1 to protect cells from apoptosis-mediated cell death in p53-deficient cells. These results suggest a higher chemotherapy susceptibility of cells disabled in both functions and they foster the concept that functional inhibition of BRCA1 may be a valuable adjunct to anticancer agents to increase the efficacy of chemotherapy in the treatment of p53-mutated cancers.

Frequency and distribution pattern of distant metastases in breast cancer patients at the time of primary presentation.

INTRODUCTION: For routine staging of patients with primary breast cancer, clinical practice guidelines of many medical societies recommend chest X-ray, liver ultrasound and bone scan. With respect to expanding health care costs and patients' psychological distress it has been supposed, that there might be a group of breast cancer patients, who do not need these imaging studies. METHODS: Four hundred and eighty-eight consecutive patients with primary breast cancer who had primary surgery at our institution and complete work-up for distant metastases including chest X-ray, liver ultrasound, and bone scan were studied. RESULTS: We found distant metastases at the time of primary diagnosis in 19 patients (3.9%). Bone metastases were found in 2.7%, liver metastases in 1.0%, and pulmonary metastases in 0.4%. However, in breast tumors smaller than 1 cm, no metastatic lesions were found, whereas 18.2% of the patients with pT4 tumors had metastases. In 2.4% of screening imaging studies, metastases were ruled out by additional imaging. CONCLUSION: Based on our data and a review of the literature, we suggest that chest X-ray, liver ultrasound and bone scan can be omitted in the staging of asymptomatic patients with pT1a or pT1b disease.

Photodynamic endometrial ablation for the treatment of dysfunctional uterine bleeding: a preliminary report.

BACKGROUND AND OBJECTIVES: To evaluate feasibility and functional effects of photodynamic endometrial ablation (PEA) in patients. STUDY DESIGN/PATIENTS AND METHODS: A total of 15 PEAs has been performed in 11 patients using topically applied 5-aminolevulinic acid (ALA) solutions and a balloon-light diffuser (160 J/cm(2), 635 nm). Uterine bleeding intensity has been determined on a daily basis 3 months prior to and up to 6 months after endometrial ablation using an analogous scale scoring from 1 (spotting) to 6 U (severe bleeding). Statistical analysis by unpaired Student's t-test. RESULTS: The mean number of bleeding units per cycle (n = 44) was 35.7 prior to PEA. The decrease in bleeding units was significant for the months 1-3 (24.4 U per cycle; P = 0.03), but not for the months 4-6 (25.9 U; P = 0.11) following PEA. CONCLUSIONS: PEA is feasible and provides a significant short-term reduction of uterine bleeding.