PURPOSE The primary objective was to determine if vaginal cuff brachytherapy and chemotherapy (VCB/C) increases recurrence-free survival (RFS) compared with pelvic radiation therapy (RT) in high-intermediate and high-risk early-stage endometrial carcinoma. PATIENTS AND METHODS A randomized phase III trial was performed in eligible patients with endometrial cancer. Eligible patients had International Federation of Gynecology and Obstetrics (2009) stage I endometrioid histology with Gynecologic Oncology Group protocol 33–based high-intermediate–risk criteria, stage II disease, or stage I to II serous or clear cell tumors. Treatment was randomly assigned between RT (45 to 50.4 Gy over 5 weeks) or VCB followed by intravenous paclitaxel 175 mg/m2 (3 hours) plus carboplatin (area under the curve, 6) every 21 days for three cycles. RESULTS The median age of the 601 patients was 63 years, and 74% had stage I disease. Histologies included endometrioid (71%), serous (15%), and clear cell (5%). With a median follow-up of 53 months, the 60-month RFS was 0.76 (95% CI, 0.70 to 0.81) for RT and 0.76 (95% CI, 0.70 to 0.81) for VCB/C (hazard ratio, 0.92; 90% confidence limit, 0.69 to 1.23). The 60-month overall survival was 0.87 (95% CI, 0.83 to 0.91) for RT and 0.85 (95% CI, 0.81 to 0.90) for VCB/C (hazard ratio, 1.04; 90% confidence limit, 0.71 to 1.52). Vaginal and distant recurrence rates were similar between arms. Pelvic or para-aortic nodal recurrences were more common with VCB/C (9% v 4%). There was no heterogeneity of treatment effect with respect to RFS or overall survival among clinical or pathologic variables evaluated. CONCLUSION Superiority of VCB/C compared with pelvic RT was not demonstrated. Acute toxicity was greater with VCB/C; late toxicity was similar. Pelvic RT alone remains an effective, well-tolerated, and appropriate adjuvant treatment in high-risk early-stage endometrial carcinomas of all histologies.

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Purpose: This study assessed the safety/tolerability, pharmacokinetics, and clinical activity of three times weekly i.v. 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in combination with once-weekly i.v. cisplatin and daily pelvic radiation in patients with gynecologic malignancies. 3-AP is a novel small-molecule inhibitor of ribonucleotide reductase (RNR) and is being tested as a potential radiosensitizer and chemosensitizer.Experimental Design: Patients with stage IB2 to IVB cervical cancer (n = 10) or recurrent uterine sarcoma (n = 1) were assigned to dose-finding cohorts of 2-hour 3-AP infusions during 5 weeks of cisplatin chemoradiation. Pharmacokinetic and methemoglobin samples and tumor biopsy for RNR activity were obtained on day 1 and day 10. Clinical response was assessed.Results: The maximum tolerated 3-AP dose was 25 mg/m 2 given three times weekly during cisplatin and pelvic radiation. Two patients experienced manageable 3-AP-related grade 3 or 4 electrolyte abnormalities. 3-AP pharmacokinetics showed a 2-hour half-life, with median peak plasma concentrations of 277 ng/mL (25 mg/m 2 ) and 467 ng/mL (50 mg/m 2 ). Median methemoglobin levels peaked at 1%(25 mg/m 2 ) and 6% (50 mg/m 2 ) at 4 hours after initiating 3-AP infusions. No change in RNR activity was found on day 1 versus day 10 in six early complete responders, whereas elevated RNR activity was seen on day 10 as compared with day 1 in four late complete responders (P = 0.02). Ten (100%) patients with stage IB2 to IVB cervical cancer achieved complete clinical response and remained without disease relapse with a median 18 months of follow-up (6-32 months). Conclusions: 3-AP was well tolerated at a three times weekly i.v. 25 mg/m 2 dose during cisplatin and pelvic radiation.

The safety and efficacy of indwelling intraperitoneal (IP) catheters for the management of refractory malignant ascites is unclear. A systematic literature overview and retrospective chart review of patients with malignant refractory ascites who underwent indwelling IP catheter placement was performed. Standardized literature abstraction and chart review templates were used to ensure that consistent information was collected. Fifteen publications met literature search criteria, representing 221 patients. Tenckhoff (Quinton Instrument Company, Seattle, WA, USA), Pleurex (Denver Biomedical Inc., Golden, CO, USA), and peritoneal catheters were used, along with IP ports. A median 5.9% of cases (range: 2.5%-34%) had documented peritonitis. In the literature, untunneled catheters were most commonly associated with infections. Our chart review added 19 cases from two academic institutions to this literature (median age: 60 years [range: 31-85]; females: 17 [89%]; gynecological malignancies: 14 [73%]). Palliative management before catheter placement included diuretics (n=4 [21%]) and multiple paracenteses (n=11 [58%] had two or more taps [range: 2-8]). Median time from diagnosis to catheter placement was 25 months (range: 1-77). Interventions were: French pigtail catheters (n=16 [84%]), Tenckhoff catheter (n=1 [5%]), and Port-A-Caths (Smith Medical MD, St. Paul, MN, USA) (n=2; 11%). Four (21%) catheters were tunneled. Prophylactic antibiotics were prescribed in six cases (32%). Two cases (11%) had documented infections, seven catheters (37%) became occluded, and two leaked (11%). The median time from catheter until death was 36 days (range: 4-660). Nine patients (47%) were admitted to hospice. In these retrospective studies, indwelling IP catheters appear to be a safe and effective palliative strategy to manage refractory malignant ascites, without overwhelming infection rates.

Increased frequency and dysregulation of telomerase activation is correlated with increasing severity of histopathologic changes, but not with HPV infection. Whether dysregulated activity is a prognostic marker for development of invasive carcinoma remains to be determined.

BACKGROUND. Ovarian cancer patients frequently receive chemotherapy near the end of life. The purpose of the current study was to develop indicators that characterize those ovarian cancer patients who have a short life span. METHODS. The medical charts of deceased epithelial ovarian cancer patients were retrospectively reviewed from 2000 through 2006. All patients received primary debulking surgery and adjuvant chemotherapy. Aggressiveness of cancer care within the last month of life was measured by chemotherapy regimens, emergency room visits, and hospitalizations. Significant clinical events (SCE) were defined as ascites, bowel obstruction, and pleural effusion. Survival quartiles were compared using chi‐square and Student t test statistics. Multiple regression analysis was performed using survival duration as a dependent variable. RESULTS. In all, 113 patients with epithelial ovarian cancer were reviewed. Patients had increased hospitalizations (P < .001) and SCE (P < .001) as they approached the end of life. There was no difference in the pattern of hospitalizations and SCE between the top and bottom survival quartiles. Patients with a shorter survival time had a trend toward increased chemotherapy during their last 3 months of life (P = .057) and had increased overall aggressiveness of care (P = .013). In patients with a disease remission, the length of initial remission time was found to be significant in predicting survival (P < .01). Time to second disease recurrence was also significant in predicting survival time (P < 0.01). CONCLUSIONS. Patients who received aggressive care did not have improvement in survival. Short disease remissions and increasing hospitalizations with SCE should be indicators of the appropriateness of reducing cure‐oriented therapies and increasing palliative interventions. Cancer 2008. ©2008 American Cancer Society.

A different series of new polystyrene–clay nanocomposites have been prepared by grafting polymerization of styrene with vinyl‐montmorillonite (MMT) clay. The synthesis was achieved through two steps. The first step is the modification of clay with the vinyl monomers, such as N,N‐dimethyl‐n‐octadecyl‐4‐vinylbenzyl‐ammonium chloride, n‐octadecyl‐4‐vinylbenzyl‐ammonium chloride, triphenyl‐4‐vinylbenzyl‐phosphonium chloride, and tri‐n‐butyl‐4‐vinylbenzyl‐phosphonium chloride. The second step is the polymerization of styrene with different ratios of vinyl‐MMT clay. The materials produced were characterized by different physical and chemical methods: (1) IR spectra, confirming the intercalation of the vinyl‐cation within the clay interlayers; (2) thermogravimetric analysis (TGA), showing higher thermal stability for PS–nanocomposites than polystyrene (PS) and higher thermal stability of nanocomposites with of phosphonium moieties than nanocomposites with ammonium moieties; (3) swelling measurements in different organic solvents, showing that the swelling degree in hydrophobic solvents increases as the clay ratio decreases; (4) X‐ray diffraction (XRD), illustrating that the nanocomposites were exfoliated at up to a 25 wt % of organoclay content; and (5) scanning electron microscopy (SEM), showing a complete dispersion of PS into clay galleries. Also, transmission electron microscopy (TEM) showed nanosize spherical particles of ∼ 150–400 nm appearing in the images. © 2006 Wiley Periodicals, Inc. J Appl Polym Sci 103: 3739–3750, 2007

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