Abstract: GOALS OF THE WORK: Osteonecrosis of the jaw (ONJ) is a severe complication of bisphosphonates treatment. Bisphosphonates reduce skeletal adverse events and give a clinical benefit to cancer patients. Therefore, it is necessary to identify appropriate procedures to reduce ONJ injures by using a successful monitoring program. In a retrospective study we analyzed the impact of a prevention program based on clinical oral cavity examination, dentists, and patients' education. The aim of the study was to evaluate if this approach might improve ONJ outcome in patients receiving pamidronate or zoledronate. MATERIALS AND METHODS: We analyzed retrospectively two different groups of patients treated at our Institution: patients treated from October 2003 to June 2005 (group A) and patients treated from June 2005 to April 2007 (group B). In June 2005 the prevention program started for all our patients. MAIN RESULTS: One hundred and eighty-six cancer patients with bone involvement, treated with bisphosphonates, were considered. Sixteen of them developed ONJ: eight before and eight after June 2005. We observed a consistent difference in the evolution of the two groups. In the first group, four patients underwent a major surgery (one partial maxillectomy, complicated by septic shock and oronasal communication; two partial mandibulectomies; and one segmental mandibular resection), with an important impairment of their quality of life; while the eight new ONJ cases, diagnosed after June 2005, were successfully treated without aggressive dental interventions, and achieved a good control of symptoms. CONCLUSIONS: Bisphosphonates-related ONJ is a frequent adverse event (8.6%). The monitoring program proved very efficient to improve the clinical outcome of ONJ, avoiding an aggressive treatment and using a conservative approach and medical therapy.
Abstract: BACKGROUND: Darbepoetin alfa, has a longer halflife than epoetin alfa (rHuEPO) due to its increased sialylated carbohydrate content and can be administered less frequently. Its advantage in terms of response is not entirely clear. PATIENTS AND METHODS: From August 2005 until October 2006, 64 anemic patients (hemoglobin < or =11.5 g/dl) with advanced metastatic cancer receiving chemotherapy (CT), median age 65 years (range 33-77), median Eastern Cooperative Oncology Group (ECOG) performance status (PS) 1 (range 0-1), were treated with subcutaneous (s.c.) darbepoetin alfa 500 microg every 3 weeks (Q3W) and a single intravenous (i.v.) dose of 125 mg of elemental iron at the beginning of the treatment period followed by an oral daily iron supplement (200 mg of elementary iron). The treatment effect was evaluated as a response (Hb increase > or =1 g/dl) or a major response (Hb increase > or =2 g/dl) after 2, 4, 6 and 8 weeks. The patients were questioned about fatigue. RESULTS: After 8 weeks of treatment, a treatment response was observed in 11 out of the 29 evaluable patients (38%) with a major response in 10%. The mean Hb change was 0 g/dl, +0.9 g/dl, +0.75 g/dl and +0.7 g/dl respectively at 2, 4, 6 and 8 weeks. Blood transfusions were required in 9 patients (31%). At baseline, 39 out of the 64 patients (61%) reported grade 1 or 2 fatigue. At 8 weeks the patients with a major response did not show any evidence of fatigue. CONCLUSION: Darbepoetin alfa Q3W is moderately effective in reducing anemia in heavily pretreated and advanced stage chemotherapy treated patients.
Abstract: Cetuximab is a chimeric immunoglobulin G1 monoclonal antibody that targets the extracellular domain of the epidermal growth factor receptor (EGFR) with high specificity and affinity. It competitively inhibits endogenous ligand binding and thereby inhibits subsequent EGFR activation. The EGFR signaling pathways regulate cell differentiation, proliferation, migration, angiogenesis and apoptosis, all of which become deregulated in cancer cells. EGFR is an important target for cancer therapy and many studies have demonstrated that cetuximab is active in several types of cancer, particularly colorectal and head and neck cancer. Cetuximab enhances the effects of many standard cytotoxic agents, including irinotecan, and in combination with chemotherapy it can elicit antitumor responses in tumors that previously failed to respond to that chemotherapy. Cetuximab also enhances radiation-induced apoptosis. On the basis of a pivotal European randomized study (the BOND study) and of 2 clinical studies conducted in the USA, cetuximab has been approved in combination with irinotecan for patients affected by EGFR-expressing metastatic colon cancer after failure with irinotecan. There have only been a few small phase II trials on first-line treatment in metastatic colorectal cancer, but the results suggest promising activity of cetuximab together with irinotecan or oxaliplatin. There is some evidence that additive efficacy can be achieved using EGFR inhibitors in combination with vascular endothelial growth factor receptor inhibitors such as bevacizumab. A correlation between response and the main toxicity (acne-like skin reaction) has been observed but is unclear. EGFR status as a specific marker for EGFR inhibitors is controversial. At the moment, EGFR expression does not appear to be a predictive factor for response to EGFR inhibitors.
Abstract: AIMS AND BACKGROUND: The purpose of the study was to evaluate the outcome of metastatic colorectal cancer patients treated, as first line, with 5-fluorouracil bolus/leucovorin + oxaliplatin, in terms of response, progression-free and overall survival. MATERIALS AND METHODS: A retrospective cohort of consecutive metastatic colorectal cancer patients, treated from 2003 to 2006, was identified and analyzed. All patients, without a central venous device, were treated with oxaliplatin + 5-fluorouracil and leucovorin. RESULTS: Twenty-five metastatic colorectal cancer patients were treated. No 3-4 grade toxicity was observed. Five of 23 patients achieved a partial response: one of them resulted in a complete response after radiofrequency and another one after surgery. Fifteen of 23 patients had stable disease (one underwent radical surgery after chemotherapy, obtaining a complete remission) and 3 had progressive disease. Median progression-free survival was 7.2 months, and median overall survival was 30 months. CONCLUSIONS: Based on this case-series study, the regimen seems to offer a good control of disease (86.9%) and can be considered as an alternative choice for patients who cannot receive continuous infusion.
Abstract: Adjuvant therapy in colorectal cancer has always been a controversy during years. Despite the fact that benefit of adjuvant therapy in stage III is clear, a more controversial question concerns efficacy in stage II. The introduction of new drugs in addition to standard regimens has some benefit, but also adds toxicity. Ongoing studies with novel targeted therapies will show their results in the next years. Other open questions include duration of therapy and whether there is a real possibility of selecting patients for treatment on the basis of prognostic factors.
Abstract: Hand-foot syndrome is a toxic effect of some chemotherapy agents such as 5-fluorouracil (5-FU), capecitabine and liposomal doxorubicin. The symptoms and signs are localized erythema and paresthesia. Floxuridine (FUDR) is an analogue of 5-FU, used for arterial hepatic infusion in patients affected by liver metastases from colorectal cancer. A patient who was treated for colorectal cancer with liver metastases underwent locoregional chemotherapy with FUDR and systemic chemotherapy with FOLFOX4. After three cycles he developed severe painful dermatitis of the right leg. Abdominal X-ray showed displacement of the catheter to the right common iliac artery. Treatment was discontinued and the patient had a rapid recovery.
