ASA404 Enters Pivotal Phase III Trial In Second-line Lung Cancer

London, UK, and Cambridge, MA — Antisoma plc announces that ‘ATTRACT-2’, a phase III trial testing ASA404 as a second-line treatment for non-small cell lung cancer (NSCLC), is now underway. This is a single pivotal study designed to support applications to market ASA404 for lung cancer patients who have received one previous round of treatment. A separate, ongoing pivotal trial, ATTRACT-1, is evaluating ASA404 in patients receiving their first treatment for NSCLC. Glyn Edwards, Antisoma’s CEO, said: “We’re delighted that our partner Novartis has decided to explore the potential of ASA404 in previously treated as well as newly diagnosed lung cancer patients. This will help to ensure that a wide range of patients could ben…

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External beam radiation results in minimal changes in post void residual urine volumes during the treatment of clinically localized prostate cancer

Background:
To evaluate the impact of external beam radiation therapy (XRT) on weekly ultrasound determined post-void residual (PVR) urine volumes in patients with prostate cancer.
Methods:
125 patients received XRT for clinically localized prostate cancer. XRT was delivered to the prostate only (n=66) or if the risk of lymph node involvement was greater than 10% to the whole pelvis followed by a prostate boost (n=59). All patients were irradiated in the prone position in a custom hip-fix mobilization device with an empty bladder and rectum. PVR was obtained at baseline and weekly. Multiple clinical and treatment parameters were evaluated as predictors for weekly PVR changes.
Results:
The mean patient age was 73.9 years with a mean pre-treatment prostate volume of 53.3 cc, a mean IPSS of 11.3 and a mean baseline PVR of 57.6 cc. During treatment, PVR decreased from baseline in both cohorts with the absolute difference within the limits of accuracy of the bladder scanner. Alpha-blockers did not predict for a lower PVR during treatment. There was no significant difference in mean PVR urine volumes or differences from baseline in either the prostate only or pelvic radiation groups (p=0.664 and p=0.458, respectively). Patients with a larger baseline PVR (>40 cc) had a greater reduction in PVR, although the greatest reduction was seen between weeks one and three. Patients with a small PVR (<40 cc) had no demonstrable change throughout treatment.
Conclusions:
prostate XRT results in clinically insignificant changes in weekly PVR volumes, suggesting that radiation induced bladder irritation does not substantially influence bladder residual urine volumes.

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2 Nutritional Items That Prevent Skin Cancer

Not everybody has a tough hide, this is evident by the number of skin cancer cases that pass through the doctors offices each year. Although early detection has decreased the fatal blow that cancer can have, prevention can always advert any further complications.

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The radiosensitizer 2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide induces DNA damage in EMT-6 mammary carcinoma cells

Background:
DCQ (2-benzoyl-3-phenyl-6,7-dichloroquinoxaline 1,4-dioxide), a synthetic quinoxaline 1,4-dioxide, enhances the cytotoxic effect of ionizing radiation (IR) in vivo and in vitro. We sought to clarify whether increased radiation-induced DNA damage, decreased rate of damage repair, and the generation of reactive oxygen species (ROS) contribute to DCQ enhancement of IR.
Methods:
Murine mammary adenocarcinoma EMT-6 cells were treated with DCQ for 4h before exposure to 10Gy IR. Treated cells were monitored for modulations in cell cycle, induction of DNA damage, and generation of ROS.
Results:
Combined DCQ and IR treatments (DCQ+IR) induced rapid cell-cycle arrests in EMT-6 cells, particularly in S and G2/M phases. Alkaline comet assays revealed high levels of DNA damage in cells after exposure to DCQ+IR, consistent with damage-induced arrest. Unlike IR-only and DCQ-only treated cells, the damage induced by combined DCQ+IR was repaired at a slower rate. Combined treatment, compared to separate DCQ and IR treatments, activated DNA-protein kinase and induced more p-ATM, supporting a role for double strand breaks (DSBs), which are more toxic and difficult to repair than single strand breaks (SSBs). Contributing factors to DCQ radiosensitization appear to be the induction of ROS and DSBs.
Conclusions:
Collectively, our findings indicate that radiosensitization by DCQ is mediated by DNA damage and decreased repair and that ROS are at least partially responsible.

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Concurrent chemo-radiotherapy following neoadjuvant chemotherapy in locally advanced breast cancer

Background:
Despite broad advances in multimodal treatment of locally advanced breast cancer (LABC), 30 to 40% of patients develop loco-regional relapse. The aim of this study was to analyze in a retrospective manner the effectiveness of concurrent chemo-radiotherapy (CCRTh) after neoadjuvant chemotherapy (NCT) in patients with LABC.
Methods:
One hundred twelve patients with LABC (stage IIB-IIIB) were treated with NCT (5-fluorouracil 500mg/m2, doxorubicin 50mg/m2, and cyclophosphamide 500mg/m2 (FAC), or doxorubicin 50mg/m2 and cyclophosphamide 500mg/m2 (AC) IV in four 21-day courses) followed by CCRTh (60Gy breast irradiation and weekly mitomycin 5mg/m2, 5-fluorouracil 500mg/m2, and dexamethasone 16mg, or cisplatin 30mg/m2, gemcitabine 100mg/m2 and dexamethasone 16mg), and 6-8 weeks later, surgery and two additional courses of FAC, AC, or paclitaxel 90mg/m2 weekly for 12 weeks, and in case of estrogen-receptor positive patients, hormonal therapy.
Results:
Stages IIB, IIIA and -B were 21.4, 42.9, and 35.7%, respectively. Pathological complete response (pCR) in the breast was 42% (95% CI, 33.2-50.5%) and, 29.5% (95% CI, 21.4-37.5%) if including both the breast and the axillary nodes. Multivariate analysis showed that the main determinant of pCR was negative estrogen-receptor status (HR=3.8; 95% CI, 1.5-9; p=0.016). The 5-year disease-free survival (DFS) was 76.9% (95% CI, 68.2-84.7%). No relationship between pCR and DFS was found. Multivariate analysis demonstrated that the main DFS determinant was clinical stage (IIB and IIIA vs. IIIB, HR=3.1; 95% CI, 1.02-9.74; p=0.04). Only one patient had local recurrence. Five-year overall survival was 84.2% (95% CI, 75-93.2%). The toxicity profile was acceptable.
Conclusions:
This non-conventional multimodal treatment has good loco-regional control for LABC. Randomized clinical trials of preoperative CCRTh following chemotherapy, in patients with LABC are warranted.

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