Amifostine: The first selective-target and broad-spectrum radioprotector

After several decades of preclinical and clinical research, the first approved radioprotective drug, amifostine, is being used in clinical practice. Amifostine has been shown to specifically protect normal tissues from damage caused by radiation and chemotherapy. An inactive prodrug, amifostine is converted to an active thiol by dephosphorylation by alkaline phosphatase in the normal endothelium. The hypovascularity and acidity of the tumor environment and the differential expression of alkaline phosphatase in normal and neoplastic tissues contribute to its cytoprotective selectivity. The cytoprotective mechanism of amifostine is complicated, involving free-radical scavenging, DNA protection and repair acceleration, and induction of cellular hypoxia. The U.S. Food and Drug Administration has approved the i.v. use of amifostine to reduce the cumulative renal toxicity associated with repeated administration of cisplatin in patients with advanced ovarian cancer and to reduce the incidence of moderate to severe xerostomia in patients undergoing postoperative radiation treatment for head and neck cancer, where the radiation port includes a substantial portion of the parotid glands. Nonetheless, amifostine has potential applications in many other oncologic settings. Novel schedules and routes of administration are under investigation and may further simplify the use of amifostine, reduce any undesired effects, and considerably broaden its applications. This review summarizes the clinical experience with amifostine and provides insight into future clinical directions. ©AlphaMed Press

Physical activity and mammographic parenchymal patterns among Greek postmenopausal women

Objective: To examine whether physical activity during the last five years is related to later breast mammographic density in postmenopausal Greek women. Methods: We designed a cross-sectional study in 724 women, of ages 45-67 years. An interview-administered questionnaire was used to obtain information on duration and intensity of recreational physical activity during five years preceding study recruitment. Mammograms were evaluated according to BIRADS classification and BIRADS score was also estimated. Multivariate ordinal logistic regression analysis was used to assess associations between physical activity index and breast density according to the BIRADS classification methods. Results: We observed a statistically significant inverse association of mammographic breast density measured by the BIRADS classification method and recreational exercise (OR = -0.10; 95% CI -0.018, -0.001; p = 0.022). For one unit increase in physical activity as expressed by the MET-h/week score, the odds of lower versus higher breast density categories are 1.105 greater, given that all of the other variables in the model are held constant. A modifying effect by age at recruitment was evident among participants, with a stronger inverse association between recreational activity and mammographic breast density among older women (OR = -0.036; 95% CI -0.063, -0.009; p = 0.009). An inverse association between physical activity and BIRADS score was evident, not reaching statistical significance (OR = 0.00; 95% CI -0.009, 0.008; p = 0.887). Conclusions: Mammographic breast area was lower in postmenopausal women who participated in sports/recreational physical activity compared to inactive controls. Increasing physical activity levels among postmenopausal women might be a reasonable approach to reduce mammographic density. However, until more physical activity and mammographic breast density studies are conducted that confirm our findings, they have to be interpreted with caution, due to the retrospective nature of our data and the possibility of memory bias. © 2011 Elsevier Ireland Ltd. All rights reserved

Phase II study of temozolomide and concomitant whole-brain radiotherapy in patients with brain metastases from solid tumors

Background: The aim of this study was to evaluate the effectiveness and possible toxicity of the combination of temozolomide (TMZ) with whole-brain irradiation (WBI) in the treatment of brain metastases from solid tumors. Patients and Methods: 33 patients with brain metastases were included in the study and treated with TMZ 60 mg/m2/day (days 1-16) concomitantly with WBI (36 Gy/12 fractions given in 16 days). One month after the end of radiotherapy, 6 cycles of TMZ were administered as adjuvant treatment (200 mg/m2/day for 5 consecutive days every 28 days). Results: Responses were assessed using computed tomography at the end of the 3rd and 6th cycle of chemotherapy. The objective response rate was 54.5% and 57.6% after the 3rd and the 6th cycle, respectively. The median overall survival was 12 months. In patients with metastases from lung cancer the objective response rate was 11/14 (78.6%) after both the 3rd and the 6th cycle of treatment. The most common side effects were anemia (24.2%), thrombocytopenia (18.2%), as well as nausea and vomiting (18.2%). The high incidence of hepatotoxicity (45.5%) might be related to concomitantly administered antiepileptic drugs and not to TMZ. Conclusion: WBI combined with TMZ as concomitant and adjuvant treatment is effective in treating brain metastases, with acceptable mild side effects. © 2007 S. Karger GmbH

Cytoreductive surgery combined with intraoperative chemo-hyperthermia and postoperative radiotherapy in the management of advanced pancreatic adenocarcinoma: Feasibility aspects and efficacy

Background/Purpose. The aim of our study was to evaluate the feasibility and the efficacy of cytoreductive surgery (CS) with intraoperative chemo-hyperthermia in the management of advanced stage IVA (T4N0M0) pancreatic cancer. Methods. From August 1995 through March 1996, seven patients with unresectable adenocarcinoma of the pancreas underwent CS, with preoperative chemotherapy (5-fluorouracil [FU] for 96h), plus 45-Gy external beam postoperative irradiation with a 6-MeV linear accelerator (1.8Gy per fraction, 5 days per week). A single session of intraoperative hyperthermia was performed with a waveguide-type applicator operating at 433MHz, and temperature was measured by inserting a flexiguide needle catheter carrying a thermometry probe with three measuring points into the tumor. The tumor region was heated to 43°C-45°C for up to 60min, while 5-FU 500mg was injected simultaneously through the gastroduodenal artery into the splenic artery (intraoperative regional chemotherapy). Results. Postoperative recovery was uneventful for all patients. After the combined treatment, there was a significant decrease in the values of both serum carcinoembryonic antigen (CEA; P = 0.017, Wilcoxon test) and carbohydrate antigen (CA)19-9 (P = 0.016; Wilcoxon test), from 7.6 ± 1.5ng/ml CEA and 869.6 ± 126.9 U/ml CA to 3.5 ± 0.8ng/ml CEA and 104.7 ± 35.4 U/ml CA19-9. Moreover, there was a significant improvement (P = 0.016; Wilcoxon test) in Eastern Cooperative Oncology Group performance status, pain score, and body mass index. The median overall survival was 18.5 (SE, 1.8) months. Conclusions. Our preliminary clinical results suggest the tolerability and the considerable potential advantage of using cytoreductive resection with preoperative chemotherapy, intraoperative chemo-hyperthermia, and external beam postoperative radiotherapy for the management of advanced adenocarcinoma of the pancreas

Granulosa cell tumor of the ovary: Tumor review

Granulosa cell tumors of the ovary are rare neoplasms that originate from sex-cord stromal cells. The long natural history of granulosa cell tumors and their tendency to recur years after the initial diagnosis are the most prominent of their characteristics. The secretion of estradiol is the reason for signs at presentation such as vaginal bleeding and precocious puberty. Abdominal pain and hemoperitoneum, which occasionally can occur, are attributable to tumor rupture. The most common finding in pelvic examination is a tumor mass, which is subsequently confirmed with imaging techniques. Surgery is the mainstay of initial management for histological diagnosis, appropriate staging, and debulking. A more conservative unilateral salpingo-oophorectomy is indicated in patients with stage I disease and patients of reproductive age. Total abdominal hysterectomy with bilateral salpingo-oophorectomy is the appropriate surgical treatment for postmenopausal women and those with more advanced disease. The stage of disease is the most important prognostic factor associated with the risk of relapse. There are no clear conclusions regarding the role of postoperative chemotherapy or radiotherapy in stage I disease and in those with completely resected tumor. The use of adjuvant chemotherapy or radiotherapy has sometimes been associated with prolonged disease-free survival and possibly overall survival. Chemotherapy is the treatment of choice for patients with advanced, recurrent, or metastatic disease, and BEP (bleomycin, etoposide, and cisplatin) is the preferred regimen. Although the overall rate of response to treatment is high, the impact of treatment on disease-free or overall survival is unknown. Prolonged surveillance is mandatory because tumors tend to recur years after the initial diagnosis. © 2008 Sage Publications

Systematic review of amifostine for the management of oral mucositis in cancer patients

Purpose: The aim of this study was to review the available literature from 1966 until December 31, 2010 and define clinical practice guidelines for the use of amifostine for the prevention and treatment of oral mucositis in cancer patients. Methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for the use of amifostine, in each cancer treatment setting was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, or no guideline possible. Results: Thirty papers were reviewed for evidence on amifostine as an intervention for oral mucositis. No guideline was possible for amifostine in any cancer treatment setting due to inadequate and conflicting evidence. Conclusion: Review of the amifostine studies for the prevention and treatment of oral mucositis has found insufficient evidence to support its use in any cancer treatment setting for this purpose. Additional well-designed research is needed to clarify the role of amifostine as an intervention for oral mucositis. © 2012 Springer-Verlag Berlin Heidelberg

Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients

Purpose: The aim of this project was to review the available literature and define clinical practice guidelines for the use of anti-inflammatory agents for the prevention and treatment of oral mucositis in cancer patients. Materials and methods: A systematic review was conducted by the Mucositis Study Group of the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. The body of evidence for use of each intervention, in each cancer treatment setting, was assigned an evidence level. Based on the evidence level, one of the following three guideline determinations was possible: recommendation, suggestion, and no guideline possible. Results: Forty-one papers were reviewed. There was sufficient evidence to recommend the use of benzydamine mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving moderate-dose radiation therapy (up to 50 Gy), without concomitant chemotherapy. A new suggestion was developed against the use of misoprostol mouthwash for the prevention of oral mucositis in head and neck cancer patients receiving radiation therapy. Positive results were reported for some other anti-inflammatory agents. However, no guidelines were able to be developed for any other agents due to insufficient and/or conflicting evidence. Conclusions: The use of anti-inflammatory agents continues to be a promising strategy for the prevention and treatment of oral mucositis. Additional well-designed studies are needed to examine the use of this class of agents for oral mucositis. © 2013 Springer-Verlag Berlin Heidelberg