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Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography and (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for recurrent prostate carcinoma: results of a prospective clinical trial.
Schuster, DM, Nieh, PT, Jani, AB, Amzat, R, Bowman, FD, Halkar, RK, Master, VA, Nye, JA, Odewole, OA, Osunkoya, AO, et al
The Journal of urology. 2014;(5):1446-53
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Abstract
PURPOSE We prospectively evaluated the amino acid analogue positron emission tomography radiotracer anti-3-[(18)F]FACBC compared to ProstaScint® ((111)In-capromab pendetide) single photon emission computerized tomography-computerized tomography to detect recurrent prostate carcinoma. MATERIALS AND METHODS A total of 93 patients met study inclusion criteria who underwent anti-3-[(18)F]FACBC positron emission tomography-computerized tomography plus (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for suspected recurrent prostate carcinoma within 90 days. Reference standards were applied by a multidisciplinary board. We calculated diagnostic performance for detecting disease. RESULTS In the 91 of 93 patients with sufficient data for a consensus on the presence or absence of prostate/bed disease anti-3-[(18)F]FACBC had 90.2% sensitivity, 40.0% specificity, 73.6% accuracy, 75.3% positive predictive value and 66.7% negative predictive value compared to (111)In-capromab pendetide with 67.2%, 56.7%, 63.7%, 75.9% and 45.9%, respectively. In the 70 of 93 patients with a consensus on the presence or absence of extraprostatic disease anti-3-[(18)F]FACBC had 55.0% sensitivity, 96.7% specificity, 72.9% accuracy, 95.7% positive predictive value and 61.7% negative predictive value compared to (111)In-capromab pendetide with 10.0%, 86.7%, 42.9%, 50.0% and 41.9%, respectively. Of 77 index lesions used to prove positivity histological proof was obtained in 74 (96.1%). Anti-3-[(18)F]FACBC identified 14 more positive prostate bed recurrences (55 vs 41) and 18 more patients with extraprostatic involvement (22 vs 4). Anti-3-[(18)F]FACBC positron emission tomography-computerized tomography correctly up-staged 18 of 70 cases (25.7%) in which there was a consensus on the presence or absence of extraprostatic involvement. CONCLUSIONS Better diagnostic performance was noted for anti-3-[(18)F]FACBC positron emission tomography-computerized tomography than for (111)In-capromab pendetide single photon emission computerized tomography-computerized tomography for prostate carcinoma recurrence. The former method detected significantly more prostatic and extraprostatic disease.
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Antiemetic therapy of fosaprepitant, palonosetron, and dexamethasone combined with cisplatin-based chemotherapy for head and neck carcinomas.
Tsukahara, K, Nakamura, K, Motohashi, R, Sato, H, Endo, M, Katsube, Y, Ueda, Y, Suzuki, M
Acta oto-laryngologica. 2014;(11):1198-204
Abstract
CONCLUSION Concomitant antiemetic therapy comprising fosaprepitant, palonosetron, and dexamethasone is effective for head and neck carcinoma. OBJECTIVE A patient diary was constructed to determine the effectiveness of concomitant antiemetic therapy with a neurokinin-1 receptor antagonist (fosaprepitant), 5-hydroxytryptamine receptor antagonist (palonosetron), and dexamethasone in accordance with guidelines. METHODS Subjects comprised 41 patients who received 71 courses of chemotherapy, along with fosaprepitant, palonosetron, and dexamethasone. A patient diary was compiled concerning the presence/absence of vomiting, vomiting episodes, presence/absence of rescue therapy, food intake, presence/absence of nausea, and general condition. RESULTS The frequency of the primary end point of complete response in the overall phase was 69.0%. The proportion of patients with no vomiting in the overall phase was 90.1%. In the acute phase, the proportion of no nausea and slight nausea together was 91.5%, no change in and slightly reduced food intake together was 87.3%, and the proportion of good general condition and relatively good general condition was 85.9%. In the delayed phase, the proportion of no nausea and slight nausea together was 56.3%, no change in and slightly reduced food intake together was 43.7%, and the proportion of good general condition and relatively good general condition together was 53.5%.
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Deposition of superparamagnetic iron-oxide nanoparticles in axillary sentinel lymph nodes following subcutaneous injection.
Johnson, L, Pinder, SE, Douek, M
Histopathology. 2013;(3):481-6
Abstract
AIMS: Superparamagnetic iron oxide nanoparticle (SPIO)-enhanced axillary lymph node magnetic resonance imaging (MRI) has the potential to supersede sentinel lymph node (SLN) biopsy in the management of early breast cancer with in vivo pre-operative metastasis detection. We evaluated the distribution and extent of SPIOs within the SLN and its impact on routine histological assessment. METHODS AND RESULTS A total of 131 SLNs from 51 consecutive patients with breast cancer were examined histologically following subcutaneous injection of 2-4 ml SPIOs. SLNs were identified intra-operatively using the combined technique. Ex vivo histological analysis was performed and the distribution of SPIOs assessed using standard haematoxylin and eosin staining. SPIO distribution was predominantly within lymph node sinuses (81%); fewer nodes contained iron in the subcapsular space (24%) and parenchyma (14%). In 58%, SPIOs were sequestered in macrophages. SPIOs were not seen within the areas of nodes containing metastases, but was seen surrounding the metastases. CONCLUSIONS Following subcutaneous injection of SPIOs, iron deposition is found predominantly in sinuses and the subcapsular space and is not found in areas containing metastases. This reinforces the notion that high resolution SPIO-enhanced MRI has the potential for in vivo metastasis in the SLN in breast cancer. Routine histological examination was unaffected.
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EUS-guided celiac ganglion irradiation with iodine-125 seeds for pain control in pancreatic carcinoma: a prospective pilot study.
Wang, KX, Jin, ZD, Du, YQ, Zhan, XB, Zou, DW, Liu, Y, Wang, D, Chen, J, Xu, C, Li, ZS
Gastrointestinal endoscopy. 2012;(5):945-52
Abstract
BACKGROUND Celiac plexus neurolysis for the palliative reduction of pain in unresectable pancreatic carcinoma (PC) is safe but provides limited relief. In a previous study, we found that EUS-guided implantation of iodine-125 ((125)I) around the celiac ganglia is a safe procedure and can induce apoptosis of local neurons in a porcine model. OBJECTIVE To evaluate the safety and efficacy of direct celiac ganglion irradiation with (125)I seeds for the relief of moderate to severe pain secondary to unresectable PC. DESIGN Prospective study. SETTING Single, tertiary care referral center. PATIENTS This study enrolled consecutive patients who had moderate to severe pain resulting from biopsy-proven unresectable PC. INTERVENTION All patients underwent EUS-guided direct celiac ganglion irradiation with (125)I seeds. Follow-up was conducted at least once weekly until death. MAIN OUTCOME MEASUREMENTS Blood parameters, Visual Analog Scale (VAS) score, mean analgesic (MS Contin [morphine sulfate]) consumption, and complications were evaluated during follow-up. RESULTS Twenty-three patients with unresectable PC underwent the procedure. The mean number of seeds implanted in the celiac ganglion per patient was 4 (range 2-6). Immediately after the procedure, pain relief and analgesic consumption showed no significant changes compared with preoperative values. Six patients (26%) reported pain exacerbation. Two weeks later, the VAS score and mean analgesic consumption were significantly less than preoperative values. No procedure-related deaths or major complications occurred. LIMITATIONS Uncontrolled study. CONCLUSIONS EUS-guided direct celiac ganglion irradiation with (125)I seeds can reduce the VAS score and analgesic drug consumption in patients with unresectable PC.
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Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer.
Dizon, DS, Damstrup, L, Finkler, NJ, Lassen, U, Celano, P, Glasspool, R, Crowley, E, Lichenstein, HS, Knoblach, P, Penson, RT
International journal of gynecological cancer : official journal of the International Gynecological Cancer Society. 2012;(6):979-86
Abstract
BACKGROUND Preclinical data show that belinostat (Bel) is synergistic with carboplatin and paclitaxel in ovarian cancer. To further evaluate the clinical activity of belinostat, carboplatin, and paclitaxel (BelCaP), a phase 1b/2 study was performed, with an exploratory phase 2 expansion planned specifically for women with recurrent epithelial ovarian cancer (EOC). METHODS Thirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m² daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m² given on day 3 of a 21-day cycle. The primary end point was overall response rate (ORR), using a Simon 2 stage design. RESULTS The median age was 60 years (range, 39-80 years), and patients had received a median of 3 prior regimens (range, 1-4). Fifty-four percent had received more than two prior platinum-based combinations, sixteen patients (46%) had primary platinum-resistant disease, whereas 19 patients (54%) recurred within 6 months of their most recent platinum treatment. The median number of cycles of BelCaP administered was 6 (range, 1-23). Three patients had a complete response, and 12 had a partial response, for an ORR of 43% (95% confidence interval, 26%-61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drug-related adverse events related to BelCaP were nausea (83%), fatigue (74%), vomiting (63%), alopecia (57%), and diarrhea (37%). With a median follow-up of 4 months (range, 0-23.3 months), 6-month progression-free survival is 48% (95% confidence interval, 31%-66%). Median overall survival was not reached during study follow-up. CONCLUSIONS Belinostat, carboplatin, and paclitaxel combined was reasonably well tolerated and demonstrated clinical benefit in heavily-pretreated patients with EOC. The addition of belinostat to this platinum-based regimen represents a novel approach to EOC therapy and warrants further exploration.
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Application of MR mammography beyond local staging: is there a potential to accurately assess axillary lymph nodes? evaluation of an extended protocol in an initial prospective study.
Baltzer, PA, Dietzel, M, Burmeister, HP, Zoubi, R, Gajda, M, Camara, O, Kaiser, WA
AJR. American journal of roentgenology. 2011;(5):W641-7
Abstract
OBJECTIVE The purpose of our study was to clinically test an extended MR mammography (MRM) protocol for combined local staging (T-staging) and locoregional staging (N-staging) of breast cancer within one single examination using a dedicated whole-body scanner. SUBJECTS AND METHODS Fifty-six consecutive primary breast cancer patients without prior treatment underwent MRM and surgicopathological N-staging. The MRM protocol (10 minutes; axial T1-weighted gradient-recalled echo; dynamic contrast-enhanced; T2-weighted; turbo spin-echo) was extended to evaluate axillary lymph nodes (90 seconds; coronal T2-weighted HASTE; T1-weighted volumetric breath-hold examination; field of view, both axillae, supraclavicular nodes, and cervical nodes). A dedicated whole-body scanner was used. First, two experienced radiologists independently rated the presence of lymph node metastasis (present or absent, weighted kappa). Second, predefined descriptors were applied by both readers to differentiate lymph node status. These were statistically analyzed using univariate chi-square statistics, sensitivity and specificity, positive likelihood ratio, diagnostic odds ratio (OR), and multivariate statistics (binary logistic-regression, receiver operating characteristics, and chi-squared automatic interaction detection [CHAID] tree). RESULTS Most significant predictors (p < 0.001) of present metastasis were "irregular margin" (diagnostic OR, 14.0), "inhomogeneous cortex" (diagnostic OR, 8.4), "perifocal edema" (positive likelihood ratio, 100) and "asymmetry" (diagnostic OR, 19.5). CHAID tree identified "asymmetry" and "irregular margin" as significant predictors (adjusted-p < 0.05) for present metastasis (PPV: 100%), whereas absence of "asymmetry" and "homogeneous internal structure" were highly predictive of absent metastasis (negative predictive value, 94.3%). Combination of significant descriptors using binary logistic regression revealed an area under the receiver operating characteristic curve of 0.93 (p < 0.001). Interrater agreement was "almost-perfect" (κ = 0.95). CONCLUSION Combined T-staging and locoregional staging (N-staging) was possible within one imaging session using the proposed protocol. Despite a minimal increase in examination time, high diagnostic accuracy and excellent interrater reliability were achieved.
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A phase II study of sorafenib in advanced uterine carcinoma/carcinosarcoma: a trial of the Chicago, PMH, and California Phase II Consortia.
Nimeiri, HS, Oza, AM, Morgan, RJ, Huo, D, Elit, L, Knost, JA, Wade, JL, Agamah, E, Vokes, EE, Fleming, GF
Gynecologic oncology. 2010;(1):37-40
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Abstract
OBJECTIVES To determine the efficacy and safety of single agent sorafenib, an oral multi-targeted tyrosine kinase inhibitor, in patients with advanced uterine carcinoma and carcinosarcoma. METHODS This multi-institutional non-randomized phase II trial enrolled two cohorts: patients with uterine carcinoma (cohort A) and uterine carcinosarcoma (cohort B). Eligibility criteria included measurable disease, 0-1 prior chemotherapy regimens, and ECOG performance status RESULTS Fifty-six patients (40 with carcinoma, 16 with carcinosarcoma) were enrolled between March 2005 and August 2007. Two (5%) patients with uterine carcinoma had a partial response (PR) and 17 (42.5%) achieved stable disease (SD). Five had SD lasting at least 4 months. The 6-month progression-free survival rate for patients with carcinoma was 29%, and the median overall survival was 11.4 months. No patients with carcinosarcoma had an objective response. Four (25%) had SD, and one had SD lasting 18 months. The 6-month progression-free survival rate was 13%, and the median overall survival was 5.0 months. Grade 3/4 drug related toxicities included: hypertension (13%), hand-foot syndrome (13%), hypophosphatemia (7%), anemia (5%), rash (5%), diarrhea (5%), thrombosis (5%), fatigue (5%) and bleeding (5%). CONCLUSION Sorafenib had minimal activity in patients with uterine carcinoma. Predictive factors for potential benefit are needed.
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[Assessment of the efficacy, safety and pharmacokinetics of SKG-02 (recombinant human TSH) in postoperative diagnosis of well-differentiated thyroid cancer--a Japanese prospective, controlled, multicenter open-label study].
Konishi, J, Tamaki, N, Nakada, K, Kusakabe, K, Maki, M, Kanbe, M, Higashi, T, Endo, K, Ikekubo, K, Yokoyama, K, et al
Kaku igaku. The Japanese journal of nuclear medicine. 2010;(4):479-96
Abstract
OBJECTIVE This study sought to assess the safety, efficacy, impact on hypothyroid symptoms, and pharmacokinetics of SKG-02 (rhTSH, thyrotropin alfa) in the diagnostic follow-up of Japanese patients with well-differentiated thyroid carcinoma (WDTC). METHODS Ten Japanese adults with WDTC were enrolled into a prospective, multicenter, open-label trial comparing diagnostic whole-body scintigraphy (dxWBS) and serum thyroglobulin (Tg) testing aided by SKG-02 versus these procedures aided by thyroid hormone withdrawal (THW). Patients were their own controls. Variables compared included scan set ability to detect radioiodine uptake by remnant or malignant thyroid tissue, scan set quality, diagnostic sensitivity of dxWBS and Tg testing alone or combined, frequency of hypothyroid signs/symptoms, and adverse events (AEs). SKG-02 pharmacokinetic variables including maximum concentration (Cmax), time to Cmax (Tmax) and the area under the time-concentration curve (AUC) were calculated. RESULTS In a blinded evaluation by an independent committee of 3 nuclear medicine experts, 70% of SKG-02 dxWBS scan sets were rated "equivalent" (n = 7) or "superior" (n = 0) to their THW counterparts in ability to detect radioiodine uptake in healthy or malignant thyroid tissue. Therefore the study exceeded its primary endpoint of a 60% equivalence/superiority rate. SKG-02 Tg testing identified 3/3 cases of disease. Hypothyroid signs/symptoms were substantially more frequent during THW than during euthyroidism permitted by SKG-02 use. SKG-02 was well-tolerated, with no severe or serious drug-related AEs. Cmax was 240.8 +/- 65.9 microIU/ml, Tmax was 28.75 +/- 14.21 hr after the first SKG-02 injection, and AUC was 11,414 +/- 3,462 microIU hr/ml in 9 patients evaluable for pharmacokinetics. CONCLUSIONS SKG-02 was safe and effective in the diagnostic follow-up of Japanese patients with WDTC, avoiding hypothyroid morbidity relative to THW. These and the pharmacokinetic findings were similar to those of overseas Phase III studies.
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Mitomycin C and etoposide in advanced colorectal carcinoma. A clinical and in vitro experience that focuses the problem of schedule dependence in combination therapy.
Seminara, P, Pastore, C, Iascone, C, Cicconetti, F, Nigita, G, Ielapi, T, Franchi, F
Chemotherapy. 2007;(3):218-25
Abstract
BACKGROUND Aim of this study was to evaluate the activity of a combination regimen of chemotherapy containing mitomycin C (MMC) and etoposide (ETO) in advanced colorectal carcinoma. METHODS Fourteen pretreated patients received MMC 2 mg/m2 and ETO 60 mg/m2, days 1-5 every 28 days. The clinical study was interrupted since no clinical response was observed in 14 patients following four courses of chemotherapy. An in vitro study was then performed on HTC-8 cell line. The cytotoxic activity of the MMC/ETO combination was tested by sulforhodamine B assay and the type of drug interaction was assessed using the method of Chou and Talalay. Cell cycle perturbations and apoptosis were evaluated by flow cytometry. RESULTS While MMC and ETO were singularly active, the simultaneous exposure of cells to both drugs and the sequence MMC-->ETO ensued in antagonistic interaction at all levels of killed cell fraction. Conversely, the sequence ETO-->MMC produced a synergistic interaction. CONCLUSIONS These results suggest that the activity of the MMC/ETO combination is highly schedule-dependent and that the experimental drug associations should be based on a preclinical rationale before clinical trials are designed.
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Phase II study of gemcitabine plus vinorelbine in the treatment of cisplatin-resistant nasopharyngeal carcinoma.
Wang, CC, Chang, JY, Liu, TW, Lin, CY, Yu, YC, Hong, RL
Head & neck. 2006;(1):74-80
Abstract
BACKGROUND A phase II study was conducted to evaluate the safety and efficacy of a gemcitabine plus vinorelbine combination (GV) for patients with cisplatin-resistant nasopharyngeal carcinoma (NPC). METHODS Thirty-nine eligible patients received vinorelbine, 20 mg/m(2), followed by gemcitabine, 1,000 mg/m(2), on days 1 and 8 of each 21-day cycle. RESULTS Grade 3/4 neutropenia and thrombocytopenia occurred in 44% and 18% of patients, respectively, but there was only one episode of febrile neutropenia. Nonhematologic toxicities were mild and did not lead to any treatment withdrawal. The overall response rate was 36% (95% confidence interval [CI], 20% to 52%) in an intent-to-treat analysis, with one complete response (3%) and 13 partial responses (33%). The median response duration, progression-free survival, and overall survival were 5.1, 5.6, and 11.9 months, respectively. CONCLUSION Given the moderately high activity and favorable toxicity profile, GV is a reasonable choice for patients with cisplatin-resistant NPC.