Glial tumors with oligodendroglial components are considered chemo-responsive. Forty newly diagnosed patients (11 anaplastic oligodendrogliomas [OD] and 29 anaplastic oligoastrocytomas [OA]) were enrolled into this multicenter, open-label, single-arm Phase II trial of first-line temozolomide (200 mg/m(2) on days 1-5 every 4 weeks for 6 cycles). The primary endpoint was 6-month progression-free survival (PFS) with response rate (RR), median PFS, and median overall survival (OS) as secondary endpoints. Of 39 evaluable patients at the 6-month time point (median follow-up, 34 months), 6-month PFS was 77% (95% confidence interval [CI], 74.5%-79.3%). There were 15 complete responses (CRs, 38%), 6 partial responses (PRs, 15%), and 9 disease stabilization (23%). The median PFS was 21 months (95% CI, 3-39 months), and the median OS was 43 months (95% CI, 20-66 months). Chromosome 1p/19q codeletions were seen in 47% (18 of 38) of the patients, and O-6-methylguanine-DNA-methyltransferase (MGMT) methylation was seen in 48% (10 of 21) of the patients. All patients with OD showed MGMT methylation and most (71%) had chromosome 1p/19q codeletions. Conversely, fewer patients with OA showed MGMT methylation (23%) or had chromosome 1p/19q codeletions (31%). The presence of either 1p/19q codeletion or MGMT methylation was associated with increased RR at 6 months but not with improved PFS or OS. Only 18% of the patients (7 of 40) experienced treatment-related grade 3/4 toxicities. This regimen was active and well tolerated. These data add to the growing body of data showing that primary chemotherapy may be an acceptable alternative to radiotherapy for patients with gliomas containing oligodendroglial histology.
The new anthracyclin, menogaril [7-(R)-0-methylnogarol], is reported to produce less cardiotoxicity than doxorubicin after multiple doses. This study was designed to assess acute hemodynamic changes during the first administration of menogaril and to relate these changes to plasma concentrations. Menogaril (200 mg/mg) was infused over 90 minutes to 4 patients with metastatic colon or prostate cancer. Cardiac output (CO) and stroke volume (SV) were measured noninvasively by Doppler ultrasound. Menogaril plasma concentrations were measured by HPLC and a 3-compartment mammillary model was used for pharmacokinetic analysis of the results. Steady-state volume of distribution, elimination clearance, and elimination half-life averaged 1,114 +/- 340 l/m2, 38 +/- 16 l/h/m2 and 40.3 +/- 30.3 hours, respectively. All patients were normotensive (baseline blood pressure = 135 +/- 10/73.5 +/- 8 mmHg) and ejection fractions were in normal range (EF = 68 +/- 7%). Transient increase in mean arterial pressure (MAP) from 93 +/- 3 to 107 +/- 4 mmHg (p < or = 0.001) were seen during and shortly after the end of menogaril infusion in all patients. Heart rate (78 +/- 5 min-1) remained constant. CO fell slightly and total peripheral resistance (TPR) increased by 36.8% in the last 2 patients. The increase in MAP was analyzed by a linear-effect model and averaged 0.028 +/- 0.017 mmHg per ng/ml of menogaril in the hypothetical biophase. The half-life for menogaril equilibration between plasma and this biophase was 41 +/- 22 minutes. We conclude that during acute administration of menogaril, blood pressure increases transiently secondary to an increase in TPR.(ABSTRACT TRUNCATED AT 250 WORDS)
Rationale: Prostate specific membrane antigen (PSMA) tracers have increased sensitivity in detection of prostate cancer compared to conventional imaging. We assessed the management impact of 18F-DCFPyL PET/CT in patients with PSA recurrence post radical prostatectomy (RP) and report early biochemical response in patients who underwent radiation treatment. Methods: One-hundred patients were enrolled into a prospective study, with a prior RP for prostate cancer, PSA 0.2-2.0ng/mL and no prior treatment. All patients underwent a diagnostic CT and 18F-DCFPyL PSMA PET/CT, and management intent was completed at 3 times points (original, post-CT and post-PSMA) and compared. Patients who underwent radiotherapy with 6-month PSA response data are presented. Results: Ninety-eight patients are reported with a median PSA 0.32 ng/mL (95% CI 0.28-0.36), with 71.4% pT3a/b disease and International Society of Urological Pathology (ISUP) grade group ≥3 in 59.2%. 18F-DCFPyL PET/CT detected disease in 46.9% of patients compared to 15.5% using diagnostic CT (PSMA PET 29.2% local recurrence and 29.6% pelvic nodal disease). Major change in management intent was higher post-PSMA vs post-CT (12.5% vs 3.2%, P = 0.010) and similarly, moderate change in intent (31.3% vs 13.7%, P = 0.001). The most common change was an increase recommendation of elective pelvic radiation (15.6% to 33.3%), nodal boost (0% to 22.9%) and concurrent androgen deprivation therapy (ADT) use (22.9% to 41.7%) from original to post-PSMA intent due to detection of nodal disease. 86 patients underwent 18F-DCFPyl guided radiotherapy. 55/86 patients did not receive ADT or ADT recovered with 18 month PSA response from 0.32 ng/mL to 0.02 ng/mL, 94.5% of patients with PSA ≤0.20ng/mL and 74.5% with PSA ≤0.03 ng/mL. Conclusion:18F-DCFPyL PET/CT has significant impact to management intent in patients being considered for salvage radiotherapy post-RP with PSA recurrence. Increased detection of disease, particularly in the pelvic lymph nodes resulted in increased pelvic irradiation and concurrent ADT use. Early results in patients who are staged with 18F-DCFPyL PET/CT-staged show favourable PSA response.
Abstract Purpose Prostate specific membrane antigen (PSMA) PET/CT is increasingly used in men with biochemical recurrence post-prostatectomy to detect local recurrence and metastatic disease at low PSA levels. The aim of this study was to assess patterns of disease detection, predictive factors and safety using 18 F-DCFPyL PET/CT versus diagnostic CT in men being considered for salvage radiotherapy with biochemical recurrence post-prostatectomy. Methods We conducted a prospective trial recruiting 100 patients with biochemical failure post-prostatectomy (PSA 0.2-2.0ng/mL) in men referred for salvage radiotherapy from August 2018 to July 2020. All patients underwent a PSMA PET/CT using the 18 F-DCFPyL tracer and a diagnostic CT. The detection rates of 18 F-DCFPyL PET/CT vs diagnostic CT were compared and patterns of disease are reported. Clinical patient and tumour characteristics were analysed for predictive utility. Thirty-day post-scan safety is reported. Results Of 100 patients recruited, 98 were suitable for analysis with a median PSA of 0.32ng/mL. 18 F-DCFPyL PET/CT was positive or equivocal in 52% compared to 19.6% for diagnostic CT. Local recurrence was detected on 18 F-DCFPyL PET/CT in 29.2%, nodal disease was seen in 29.6% and bony metastases in 7.1%. Both ISUP grade group (p = 0.003) and pre-scan PSA (p = 0.061) were significant predictors of 18 F-DCFPyL PET/CT positivity, and logistic regression generated probabilities combining the two showed improved prediction rates. No significant safety events were reported post 18 F-DCFPyL administration. Conclusions 18 F-DCFPyL PET/CT increases detection of disease in men with biochemical recurrence post-prostatectomy compared to diagnostic CT. Men being considered for salvage radiotherapy with a PSA > 0.2ng/mL should be considered for 18 F-DCFPyL PET/CT scan. Clinical Trial Registration Australian New Zealand Clinical Trials Registry Number: ACTRN12618001530213. Registration date 13.9.2018 http://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=375932&isReview=true
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