Anaplastic thyroid cancer (ATC), a rare highly vascularized tumor, has a dismal outcome. We conducted an open-label study of doublet carboplatin/paclitaxel chemotherapy with or without fosbretabulin ...in patients with ATC.
Patients were randomly assigned in a 2:1 ratio to 6 cycles of paclitaxel 200 mg/m(2) followed by carboplatin AUC 6 on day 1 every 3 weeks (CP), or these drugs were given on day 2 after fosbretabulin 60 mg/m(2) (CP/fosbretabulin) on days 1, 8 and 15. After 6 cycles, patients on the fosbretabulin arm without progression could continue to receive fosbretabulin on days 1 and 8 of a 3-week schedule until progression. The primary end point was overall survival (OS).
Eighty patients were assigned (planned, 180) when enrollment was stopped due to rarity of disease and very low accrual. Median OS was 5.2 months 95% confidence interval (CI) 3.1, 9.0 for the CP/fosbretabulin arm (n=55; hazard ratio 0.73 95% CI 0.44, 1.21) and 4.0 months 95% CI 2.8, 6.2 for the CP arm (n=25; p=0.22 log rank test). One-year survival for CP/fosbretabulin versus CP was 26% versus 9%, respectively. There was no significant difference in progression-free survival between the two arms. Grade 1-2 hypertension and grade 3-4 neutropenia were more common with CP/fosbretabulin. There were no significant adverse cardiovascular side effects.
Although the study did not meet statistical significance in improvement in OS with the addition of fosbretabulin to carboplatin/paclitaxel, it represents the largest prospective randomized trial ever conducted in ATC. The regimen is well tolerated, with AEs and deaths primarily related to ATC and disease progression.
Abstract Purpose To evaluate dose reduction caused by the implantation of an interstitial inflatable and biodegradable balloon device aiming to achieve lower rectal doses with virtual 3D conformal ...external beam radiation treatment. Materials and methods An inflatable balloon device was placed, interstitially and under transrectal ultrasound guidance, into the rectal–prostate interspace prior treatment initiation of 26 patients with localized prostate cancer, who elected to be treated with radiotherapy (3D CRT or IMRT). The pre- and post-implant CT imaging data of twenty two patients were collected (44 images) for the purpose of the 3D conformal virtual planning presented herein. Results The dorsal prostate–ventral rectal wall separation resulted in an average reduction of the rectal V70% by 55.3% (±16.8%), V80% by 64.0% (±17.7%), V90% by 72.0% (±17.1%), and V100% by 82.3% (±24.1%). In parallel, rectal D2 ml and D0.1 ml were reduced by 15.8% (±11.4%) and 3.9% (±6.4%), respectively. Conclusions Insertion of the biodegradable balloon into the prostate–rectum interspace is similar to other published invasive procedures. In this virtual dose distribution analysis, the balloon insertion resulted in a remarkable reduction of rectal volume exposed to high radiation doses. This effect has the potential to keep the rectal dose lower especially when higher than usual prostate dose escalation protocols or hypo-fractionated regimes are used. Further prospective clinical investigations on larger cohorts and more conformal radiation techniques will be necessary to define the clinical advantage of the biodegradable interstitial tissue separation device.
Objectives/Hypothesis:
To investigate whether curcumin enhances the cytotoxic effect of radiotherapy in head and neck squamous cell carcinoma (HNSCC).
Methods:
HNSCC cell lines SCC‐1, SCC‐9, KB, as ...well as A431 cell line were treated with curcumin, irradiation, or their combination. Cell viability was evaluated by XTT assay. Cyclooxygenase‐2 (COX‐2), epithelial growth factor receptor (EGFR), and p‐Erk1/2 were measured by Western blot analysis. CD‐1 athymic nude mice with orthotopic implanted SCC‐1 cells, were treated with control diet, curcumin containing diet, local single‐dose radiation, or combination.
Results:
Curcumin (IC50 range, 15–22 μM) and radiation inhibited cell viability in all cell lines were tested. The combination of curcumin and radiation resulted in additive effect. Curcumin decreased COX‐2 expression and inhibited phosphorylation of EGFR in SCC‐1 cells. In tumor‐bearing mice the combination regimen showed a decrease in both tumor weight (25%, P = .09) and tumor size (15%, P = .23) compared to the nontreated mice.
Conclusions:
Curcumin inhibited HNSCC cell growth and augmented the effect of radiation in vitro and in vivo. A possible mechanism is inhibition of COX‐2 expression and EGFR phosphorylation. Laryngoscope, 2009
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality. Curcumin is involved in various biological pathways leading to inhibition of NSCLC growth. The purpose of this ...study was to evaluate the effect of curcumin on expression of nuclear factor κB-related proteins in vitro and in vivo and on growth and metastasis in an intralung tumor mouse model.
H1975 NSCLC cells were treated with curcumin (0–50μM) alone, or combined with gemcitabine or cisplatin. The effects of curcumin were evaluated in cell cultures and in vivo, using ectopic and orthotopic lung tumor mouse models. Twenty mice were randomly selected into two equal groups, one that received AIN-076 control diet and one that received the same food but with the addition of 0.6% curcumin 14days prior to cell implantation and until the end of the experiment. To generate orthotopic tumor, lung cancer cells in Matrigel were injected percutaneously into the left lung of CD-1 nude mice. Western blot analysis showed that the expressions of IkB, nuclear p65, cyclooxygenase 2 (COX-2) and p-ERK1/2 were down-regulated by curcumin in vitro. Curcumin potentiated the gemcitabine- or cisplatin-mediated antitumor effects. Curcumin reduced COX-2 expression in subcutaneous tumors in vivo and caused a 36% decrease in weight of intralung tumors (P=.048) accompanied by a significant survival rate increase (hazard ratio=2.728, P=.036). Curcumin inhibition of COX-2, p65 expression and ERK1/2 activity in NSCLC cells was associated with decreased survival and increased induction of apoptosis. Curcumin significantly reduced tumor growth of orthotopic human NSCLC xenografts and increased survival of treated athymic mice. To evaluate the role of curcumin in chemoprevention and treatment of NSCLC, further clinical trials are required.
Several studies suggested that curcumin inhibits growth of malignant cells via inhibition of cyclooxygenase-2 (COX-2) activity. Other studies indicated that epidermal growth factor receptor (EGFR) is ...also inhibited by curcumin in vitro and in vivo. Moreover, recent investigations revealed an intracellular cross-talk between EGFR signaling and the COX-2 pathway. Our aim was to evaluate whether the curcumin inhibitory effect on the survival of cancer cells is associated with simultaneous down-regulation of COX-2 and EGFR and inhibition of Erk1/2 (extra-cellular signal regulated kinase) signaling pathway.
Lung and pancreas adenocarcinoma cell lines co-expressing COX-2 and EGFR (PC-14 and p34, respectively) and those expressing EGFR but deficient in COX-2 (H1299 and Panc-1, respectively) were exposed for 72 h to curcumin (0-50 microM). Cell viability was assessed by the XTT assay. Apoptosis was determined by FACS analysis. COX-2, EGFR, ErbB-2 and p-Erk1/2 expressions were measured by Western blot analysis.
Curcumin's inhibitory effect on survival and apoptosis of lung and pancreatic adenocarcinoma cell lines was significantly higher in the COX-2-expressing cells than in the COX-2-deficient cells. In the p34 and PC-14 cells, curcumin decreased COX-2, EGFR and p-Erk1/2 expressions in a dose-dependent manner. However, in the Panc-1 and H1299 cell lines, which did not express COX-2, curcumin did not affect EGFR levels.
Curcumin co-inhibited COX-2 and EGFR expression and decreased Erk1/2 activity. This inhibition was associated with decreased survival and enhanced induction of apoptosis in lung and pancreatic adenocarcinoma cells.