Is overcoming hormone resistance in breast cancer possible?

The administration of hormones plays a major role in the treatment of hormone receptor-expressing breast cancers (BCs), both in the adjuvant setting as well as in advanced disease. Hormone-responsive tumors almost uniformly develop resistance, either independently or as a result of exposure to hormones. Overcoming this phenomenon constitutes a perpetual challenge to researchers and clinical oncologists. Understanding the mechanisms leading to hormone resistance is crucial to its inhibition or, at least, its delayed onset. This manuscript provides a brief review of this topic.

Low-dose capecitabine in breast cancer patients with symptomatic bone marrow infiltration: a case study.

BACKGROUND: The prognosis of patients with metastatic breast cancer and symptomatic bone marrow involvement is poor. The aim of treatment to these patients is palliation. In this study, we sought to determine the efficacy of therapy with low doses of capecitabine in this subgroup of patients. PATIENTS AND METHODS: Five consecutive breast cancer patients with overt bone marrow involvement were treated by low doses of capecitabine in our department. Four out of five patients also received bisphosphonates to palliate skeletal symptoms. The influence of this therapeutic regimen on tumor response, blood count normalization and overall survival was analysed. RESULTS: All patients except one responded in terms of their haematological profile within two months of the initiation of treatment. Duration of haematological response was 8+ months for all patients. In two of them, tumor response in other sites was evaluated as stable disease, in one as partial remission and in one as progressive disease. Two patients survived more than 22 months without bone marrow failure. CONCLUSION: These initial results are very encouraging for this subset of patients with poor prognosis and limited life expectancy. The administration of capecitabine might be an efficient alternative treatment option. Our results merit further investigation.

First-line chemotherapy with fluorouracil-epirubicin-navelbine (FEN) combination in advanced breast cancer.

BACKGROUND: A phase II study was carried out to determine the safety and efficacy of the combination of vinorelbine, epirubicin and 5-fluorouracil (FEN) as first-line chemotherapy in advanced breast cancer (BC). PATIENTS AND METHODS: Thirty-four women with advanced BC, aged 32-75 years (median 59), previously untreated for recurrence, were enrolled in the study. The treatment consisted of fluorouracil 600 mg/m2 on day 1, epirubicin 75 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, every 3 weeks, up to a maximum of 9 cycles. RESULTS: The efficacy appeared favourable with 18 objective responses (3 complete and 15 partial) and 9 disease stabilizations, giving an overall response rate of 53% (95% CI: 36-70). The median progression-free and overall survival was 6 and 18 months, respectively (95% CI: 4.8-7.8 and 16.2-22.2, respectively). Toxicity was acceptable; the main grade 3/4 toxicity was alopecia in 94% of patients, neutropenia in 44% and less frequently gastrointestinal toxicity (9%), anaemia (6%), mucositis (6%), thrombocytopenia (3%) and diarrhoea (3%). No treatment-related death occurred, CONCLUSION: Our results suggest that FEN, as first-line chemotherapy, is an active and well-tolerated treatment for patients with advanced breast cancer.

Prevention of vinorelbine phlebitis with cimetidine. A two-step design study.

One hundred eighteen patients with various malignancies received a total of 847 vinorelbine (VNR) infusions, during 25 of which episodes of vinorelbine phlebitis occurred (1 in each of the 25 patients concerned). Venous irritation was graded with reference to the scale devised by Rittenberg et al. To prevent these 25 patients against further venous toxicity, we pretreated them with cimetidine 200 mg i.v. prior to VNR administration in subsequent cycles of chemotherapy. In most (19, or 76%) complete prevention of recurrent phlebitis was observed, while partial prevention was observed in 5 patients (20%). Treatment was unsuccessful in 1 patient. In 127 VNR infusions given after cimetidine prophylaxis only 7 (6%) episodes of phlebitis occurred. These data show that i.v. administration of cimetidine prior to vinorelbine infusion can successfully prevent recurrence of phlebitis in patients who have shown venous irritation upon prior VNR treatment, at a rate of 94%.