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Background: We have already reported on fixed-dose-rate gemcitabine (FDR-Gem) in advanced, inoperable pancreatic ductal adenocarcinoma (PDAC) and biliary tract cancer (BTC) in the context of a formal phase II study; building on that experience, we have now expanded the study to reach a cumulative accrual of 106 patients., Methods: One hundred six patients (PDAC/BTC, 75/31) were treated with weekly FDR-Gem (1,000 mg/m(2) infused at 10 mg/m(2) per minute). Patient characteristics included: male-to-female ratio, 0.83; median age, 63 years (range, 28-82); metastatic disease in 66% of patients; and an Eastern Cooperative Oncology Group performance status (ECOG PS) score of 0-1 in 81% of patients., Results: The median and total number of treatment weeks delivered were 8 (range, 2-22) and 1,154, respectively. Thirteen percent of patients achieved an objective response, 42% experienced a positive clinical benefit response, and 54% achieved a >50% reduction in serum cancer antigen (CA)19.9 levels. The median progression-free survival (PFS) and overall survival (OS) times for the entire population were 4.4 months (95% confidence interval [CI], 3.5-5.1 months) and 7.7 months (95% CI, 6.3-8.8 months), respectively, with 20% of patients alive at 1 year. On multivariate analysis, a CA19.9 reduction >50% and baseline ECOG PS score of 0 were the only independent predictors of PFS and OS, respectively. Treatment was well tolerated, with grade 3-4 neutropenia in 47 of 1,154 treatment weeks (4.1%), and grade 3 anemia and thrombocytopenia in 8 of 1,154 (0.7%) and 16 of 1,154 (1.4%) treatment weeks, respectively., Conclusions: Currently available evidence, including this updated analysis, supports the use of FDR-Gem as a first-line option in advanced PDAC, and possibly in BTC, patients and prompts the continued evaluation of this approach in combination regimens.

Background: Intravenous bisphosphonates are the current standard of care for the treatment of hypercalcemia of malignancy and for the prevention of skeletal complications associated with bone metastases. Recently, retrospective case studies have reported an association between long-term bisphosphonate therapy and osteonecrosis of the jaws., Patients and Methods: The data for twelve patients, referred to either an oral and maxillofacial surgeon or to an oral medicine specialist for the management of clinically apparent chronic oral osteonecrosis of unknown etiology, were reviewed. All had received cancer-related therapy simultaneously with bisphosphonate management., Results: The typical presenting symptoms were pain and exposed bone at the site of a previous tooth extraction. In most patients, the lesions initially occurred after dental extraction or other odontostomatological procedures, while five had a spontaneous event. Biopsy of the involved area showed the presence of necrotic lacunae, with infiltration of lymphocytes and histiocytes. In nine cases, there was histological or cytological diagnosis of suspicious osteomyelitis. No correlation was observed between the intraoral lesions and myelosuppression secondary to antineoplastic therapy., Conclusion: Based on the patients' respective histories, clinical presentations and responses to surgical and antibiotic treatments, it appears that the pathogenesis of this osteonecrotic process is most consistent with localized vascular insufficiency. In our opinion, the mechanism by which bisphosphonates compromise bone vascularity may be related to their effect on the osteoclasts. The potent bisphosphonate-mediated inhibition of osteoclast function serves to decrease bone resorption and inhibit normal bone turnover remodeling, resulting in microdamage accumulation and a reduction in some mechanical properties of the bone.

Angiogenesis, the process of generating new capillary blood vessels, is a fundamental requirement for normal physiological processes including embryogenesis, reproductive function and wound healing. Angiogenesis is also implicated in various pathological conditions including age-related retinal macular degeneration, diabetic retinopathy, rheumatoid arthritis, psoriasis and cancer growth and metastasis. Vascular endothelial growth factor (VEGF) is one of the best characterized of the pro-angiogenic growth factors, and multiple strategies have been developed to inhibit this pathway. Bevacizumab, a monoclonal antibody developed against VEGF, has shown initial preclinical and clinical activity. This review discusses the critical role of VEGF and summarizes the available data on the use of bevacizumab in colorectal cancer.

The incidence and severity of anaemia in gynaecological cancer patients depends on several factors including age, histology and tumor stage, site of neoplasm and treatment. At present, two principal opinions are available for the management of chronic anaemia in cancer patients: blood transfusions and treatment with recombinant human Erythropoietin (rHuEPO). Clinical studies showed that rHuEPO can ameliorate chronic and chemotherapy-induced anaemia and reduce transfusions in patients with various malignant diseases. In this review we discuss the role of alfa-epoetin in the management of gynaecological and breast cancers.