Abstract BACKGROUND : Abiraterone acetate is an effective drug for castration-resistant prostate cancer, but cardiac serious adverse events (SAEs) may occur. We studied their association with ...N-terminal pro–brain natriuretic peptide (NT-proBNP) and troponin T (TnT) during abiraterone therapy. PATIENTS AND METHODS : In a single institution, 17 patients were treated with abiraterone acetate 1 g daily with concomitant prednisone and then switched to dexametasone plus canrenone. Blood samples for PSA, NT-proBNP, and TnT were obtained at baseline and after 1, 3, and 6 months. RESULTS : Five patients (29.4%) experienced G3 to 4 cardiac SAEs after a median of 13 weeks (range, 9-32), including pulmonary edema, heart failure, acute coronary syndrome, sinus bradycardia with syncope, and pulmonary edema. At baseline, 4 weeks, and 3 months, median NT-proBNP and TnT levels were higher in patients with subsequent cardiac SAEs ( P = .03 and P = .04 for NT-proBNP and TnT at 3 months, respectively). After switching to dexametasone and introducing canrenone, no additional cardiac SAEs were noted. Overall response rate was 67%. CONCLUSIONS : Our study suggests a higher than expected risk of cardiac SAEs during abiraterone treatment which may well be due to the small sample size and the unrestricted entry criteria. However, baseline and frequent NT-proBNP and TnT monitoring predicted a higher risk for cardiac SAE. Larger studies should confirm our findings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: Superficial (papillary) bladder cancer is associated with progression and death from muscle-invasive bladder cancer,
but no reliable predictors of the outcomes have been identified.
...Methods: We analyzed the long-term prognostic effect of DNA flow cytometry in bladder washings from 93 subjects with previously
resected T a and T 1 bladder tumors who participated in a chemoprevention trial of the synthetic retinoid fenretinide. Kaplan-Meier analysis and
Cox regression were used to determine the prognostic effect of DNA aneuploidy on cancer progression and mortality in conjunction
with conventional clinical factors after a median of 11.5 years (interquartile range, 9.5-11.7 years).
Results: Overall, 58 of 93 (62%) specimens were DNA aneuploid at baseline. Progression-free survival was significantly shorter
in subjects with stage T 1 hazard ratio (HR), 31.6; 95% confidence interval (95% CI), 2.6-386.1; P < 0.001 and in subjects with baseline DNA aneuploid washing (HR, 10.5; 95% CI, 1.1-126.1; P = 0.03). The risk of death was also greater for stage T 1 tumors (HR, 2.6; 95% CI, 1.04-6.7; P = 0.04). DNA aneuploidy was a significant prognostic factor also for overall survival (HR, 2.8; 95% CI, 1.0-9.0; P = 0.05). Fenretinide treatment had no significant effect on cancer progression and death.
Conclusions: DNA aneuploidy in washings from endoscopically normal bladder is a significant predictor of progression and death
in addition to tumor stage. This biomarker may help to identify and monitor a high-risk group who may benefit from a chemoprevention
intervention. (Cancer Epidemiol Biomarkers Prev 2007;16(5):979–83)
The addition of bevacizumab to standard chemotherapy prolongs progression free survival in the first line treatment of epithelial ovarian cancer (EOC), but its cost/effectiveness is debated. We ...assessed the safety and activity of a lower dose of bevacizumab in pretreated advanced stage EOC.
We treated 15 patients, mostly with platinum resistant EOC, who had received a median of four prior cytotoxic regimens, with bevacizumab 5-7.5 mg/kg q21 days in combination with either carboplatin (n = 8), oral cyclofosfamide (n = 5) or weekly paclitaxel (n = 2). Bevacizumab was administered until disease progression. Tumor response was assessed by CA125 and fusion 18 F-FDG PET/contrast enhanced CT.
The median number of bevacizumab cycles was 21 (range 3-59). The median baseline CA125 was 272 U/ml and decreased to 15.2 U/ml at nadir. Tumor response was 4 complete response (CR) (26.7%) and 7 partial response (PR) (46.7%) by chemotherapy (CT), with an overall response rate of 73.4% (95% CI, 51.0 - 95.8) according to Response Evaluation Criteria In Solid Tumors (RECIST), and 6 CR (40%) and 4 PR (26.7%) by PET, for an overall metabolic response rate of 67% (95%CI, 42.8 - 90.6) according to PET Response Criteria in Solid Tumors (PERCIST). Median progression free survival (PFS) was 21 months and median overall survival (OS) was 24 months. Grade 3 adverse events related to bevacizumab were hypertension (n = 2), proteinuria (n = 1) and epistaxis (n = 5). Treatment was delayed in five patients for nasal bleeding or uncontrolled hypertension.
Low-dose bevacizumab and chemotherapy was well tolerated and active in a heavily pretreated population of advanced EOC. Further studies should assess the activity of low dose bevacizumab in EOC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
5.
64CuCl2 PET/CT in Prostate Cancer Relapse Piccardo, Arnoldo; Paparo, Francesco; Puntoni, Matteo ...
The Journal of nuclear medicine (1978),
03/2018, Volume:
59, Issue:
3
Journal Article
Peer reviewed
Open access
Our objective was to evaluate the biodistribution, kinetics, and radiation dosimetry of 64CuCl2 in humans and to assess the ability of 64CuCl2 PET/CT to detect prostate cancer (PCa) recurrence in ...patients with biochemical relapse. Methods: We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external-beam radiation therapy. All patients underwent 64CuCl2 PET/CT, 18F-choline PET/CT, and multiparametric MRI within 15 d of each other. Experienced readers interpreted the images, and the detection rate (DR) of each imaging modality was calculated. Histopathology, when available; clinical or laboratory response; and multidisciplinary follow-up were used to confirm the site of disease. In parallel, biodistribution, kinetics of the lesions, and radiation dosimetry of 64CuCl2 were evaluated. Results: From a dosimetric point of view, an administered dose of 200 MBq for 64CuCl2 translated into a 5.7-mSv effective dose. Unlike 18F-choline, 64CuCl2 was not excreted or accumulated in the urinary tract, thus allowing thorough pelvic exploration. The maximum 64CuCl2 uptake at the sites of PCa relapse was observed 1 h after tracer injection. In our cohort, 64CuCl2 PET/CT proved positive in 41 of 50 patients, with an overall DR of 82%. The DRs of 18F-choline PET/CT and multiparametric MRI were 56% and 74%, respectively. The difference between the DRs of 64CuCl2 PET/CT and 18F-choline PET/CT was statistically significant (P < 0.001). Interestingly, on considering prostate-specific antigen (PSA) value, 64CuCl2 PET/CT had a higher DR than 18F-choline PET/CT in patients with a PSA of less than 1 ng/mL. Conclusion: The biodistribution of 64CuCl2 is more suitable than that of 18F-choline for exploring the pelvis and prostatic bed. The 64CuCl2 effective dose is like those of other established PET tracers. In patients with biochemical relapse and a low PSA level, 64CuCl2 PET/CT shows a significantly higher DR than 18F-choline PET/CT.
64 CuCl 2 PET/CT in Prostate Cancer Relapse Piccardo, Arnoldo; Paparo, Francesco; Puntoni, Matteo ...
Journal of Nuclear Medicine,
03/2018, Volume:
59, Issue:
3
Journal Article
Peer reviewed
Our objective was to evaluate the biodistribution, kinetics, and radiation dosimetry of
CuCl
in humans and to assess the ability of
CuCl
PET/CT to detect prostate cancer (PCa) recurrence in patients ...with biochemical relapse.
We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external-beam radiation therapy. All patients underwent
CuCl
PET/CT,
F-choline PET/CT, and multiparametric MRI within 15 d of each other. Experienced readers interpreted the images, and the detection rate (DR) of each imaging modality was calculated. Histopathology, when available; clinical or laboratory response; and multidisciplinary follow-up were used to confirm the site of disease. In parallel, biodistribution, kinetics of the lesions, and radiation dosimetry of
CuCl
were evaluated.
From a dosimetric point of view, an administered dose of 200 MBq for
CuCl
translated into a 5.7-mSv effective dose. Unlike
F-choline,
CuCl
was not excreted or accumulated in the urinary tract, thus allowing thorough pelvic exploration. The maximum
CuCl
uptake at the sites of PCa relapse was observed 1 h after tracer injection. In our cohort,
CuCl
PET/CT proved positive in 41 of 50 patients, with an overall DR of 82%. The DRs of
F-choline PET/CT and multiparametric MRI were 56% and 74%, respectively. The difference between the DRs of
CuCl
PET/CT and
F-choline PET/CT was statistically significant (
< 0.001). Interestingly, on considering prostate-specific antigen (PSA) value,
CuCl
PET/CT had a higher DR than
F-choline PET/CT in patients with a PSA of less than 1 ng/mL.
The biodistribution of
CuCl
is more suitable than that of
F-choline for exploring the pelvis and prostatic bed. The
CuCl
effective dose is like those of other established PET tracers. In patients with biochemical relapse and a low PSA level,
CuCl
PET/CT shows a significantly higher DR than
F-choline PET/CT.
Our objective was to evaluate the biodistribution, kinetics, and radiation dosimetry of 64CuCl2 in humans and to assess the ability of 64CuCl2 PET/CT to detect prostate cancer (PCa) recurrence in ...patients with biochemical relapse. Methods: We prospectively evaluated 50 PCa patients with biochemical relapse after surgery or external-beam radiation therapy. All patients underwent 64CuCl2 PET/CT, 18F-choline PET/CT, and multiparametric MRI within 15 d of each other. Experienced readers interpreted the images, and the detection rate (DR) of each imaging modality was calculated. Histopathology, when available; clinical or laboratory response; and multidisciplinary follow-up were used to confirm the site of disease. In parallel, biodistribution, kinetics of the lesions, and radiation dosimetry of 64CuCl2 were evaluated. Results: From a dosimetric point of view, an administered dose of 200 MBq for 64CuCl2 translated into a 5.7-mSv effective dose. Unlike 18F-choline, 64CuCl2 was not excreted or accumulated in the urinary tract, thus allowing thorough pelvic exploration. The maximum 64CuCl2 uptake at the sites of PCa relapse was observed 1 h after tracer injection. In our cohort, 64CuCl2 PET/CT proved positive in 41 of 50 patients, with an overall DR of 82%. The DRs of 18F-choline PET/CT and multiparametric MRI were 56% and 74%, respectively. The difference between the DRs of 64CuCl2 PET/CT and 18F-choline PET/CT was statistically significant (P < 0.001). Interestingly, on considering prostate-specific antigen (PSA) value, 64CuCl2 PET/CT had a higher DR than 18F-choline PET/CT in patients with a PSA of less than 1 ng/mL. Conclusion: The biodistribution of 64CuCl2 is more suitable than that of 18F-choline for exploring the pelvis and prostatic bed. The 64CuCl2 effective dose is like those of other established PET tracers. In patients with biochemical relapse and a low PSA level, 64CuCl2 PET/CT shows a significantly higher DR than 18F-choline PET/CT.
Background:
The nasal cavity is a vulnerable zone which may be damaged by vascular disorders. We systematically assessed the frequency and severity of nasal cavity alterations during bevacizumab ...treatment, to determine its clinical relevance and factors contributing to its onset.
Patients and methods:
We conducted a hospital-based cohort study in 47 consecutive patients with advanced cancers who were on treatment with chemotherapy and bevacizumab at different doses. All patients underwent otolaryngology (ENT) examination at the time of study initiation.
Results:
The mean number of cycles at first ENT examination was 16 (standard deviation = 14). A total of 45 patients (96%) showed nose mucosal lesions, of whom 30% had erosions and 62% had grade 1 - 2 epistaxis. One patient had septal perforation. Grades 1 - 4 sinus disorders were noted in 60%. There was a significant trend to a higher risk of grade ≥ 2 nasal events for bevacizumab doses > 7.5 mg/kg, concomitant taxane use and digital nasal self-manipulation.
Conclusions:
We found a high incidence of nasal cavity lesions in patients receiving bevacizumab, with evidence for a dose-related effect. Most cases were low grade and manageable without drug interruption, but severe toxicity may rarely occur. Oncologists should be aware of this unusual event.
Inflammation and oxidative stress play a crucial role in the development of colorectal cancer (CRC) and interference with these mechanisms represents a strategy in CRC chemoprevention. Allopurinol, a ...safe molecular scavenger largely used as antigout agent, has been shown to increase survival of patients with advanced CRC and to reduce CRC incidence in long-term gout users in epidemiologic studies. We conducted a randomized, double-blind, placebo-controlled preoperative trial in subjects with colorectal adenomatous polyps to assess the activity of allopurinol on biomarkers of colorectal carcinogenesis. After complete colonoscopy and biopsy of the index polyp, 73 subjects with colorectal adenomas were assigned to either placebo or one of two doses of allopurinol (100 mg or 300 mg) and treated for four weeks before polyp removal. Change of Ki-67 labeling index in adenomatous tissue was the primary endpoint. Secondary endpoints were the immunohistochemical (IHC) expression of NF-κB, β-catenin, topoisomerase-II-α, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) in adenomatous polyps and normal adjacent colonic tissue. Compared with placebo, Ki-67 levels were not significantly modulated by allopurinol, whereas β-catenin and NF-κB expression levels decreased significantly in adenomatous tissue, with a mean change from baseline of -10.6%, 95% confidence interval (CI), -20.5 to -0.7, and -8.1%, 95% CI, -22.7 to 6.5, respectively. NF-κB also decreased significantly in normal adjacent tissue (-16.4%; 95% CI, -29.0 to -3.8). No dose-response relationship was noted, except for NF-κB expression in normal tissue. Allopurinol can inhibit biomarkers of oxidative activation in colon adenomatous polyps and normal adjacent tissue. Further studies should define its potential chemopreventive activity.
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