The BEACOPP chemotherapy regimen for advanced Hodgkin's disease employs a rearranged schedule permitting a shortened three-week cycle. With haematological growth factor support, the dosages of cyclophosphamide, etoposide and adriamycin could be moderately escalated. The 3-armed multicentre HD9 trial (recruitment 1993-1998; 1300 patients randomised) aimed to compare BEACOPP with the standard COPP/ABVD chemotherapy and to detect and measure the gain in efficacy, if any, due to moderate dose escalation of BEACOPP. Eight cycles were given, followed by local irradiation. The most recent interim analysis, with 689 evaluable patients, circa 40% of all expected events and a median observation time of 27 months, showed significant differences in progression rate (P) and in two-year freedom from treatment failure (F) between the treatment arms, with escalated BEACOPP (P = 2%, F = 89%) better than baseline BEACOPP (P = 9%, F = 81%) better than COPP/ABVD (P = 13%, F = 72%). Survival was not significantly different. Acute toxicity was more severe due to dose escalation, but remained manageable. These preliminary results suggest that BEACOPP improves efficacy. Moderate dose escalation is feasible with G-CSF support and appears likely to make a worthwhile improvement in the cure rate. The results must await confirmation (or otherwise) by the final analysis including all randomised patients and sufficiently mature data.
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http://dx.doi.org/10.1093/annonc/9.suppl_5.s67 | DOI Listing |
J Clin Oncol
January 2025
Center for Cell Engineering, Sloan Kettering Institute, New York, NY.
Purpose: We designed a CD19-targeted chimeric antigen receptor (CAR) comprising a calibrated signaling module, termed 1XX, that differs from that of conventional CD28/CD3ζ and 4-1BB/CD3ζ CARs. Preclinical data demonstrated that 1XX CARs generated potent effector function without undermining T-cell persistence. We hypothesized that 1XX CAR T cells may be effective at low doses and elicit minimal toxicities.
View Article and Find Full Text PDFBackground: Radio-chemotherapy remains the mainstay of glioblastoma first-line treatment after extended surgery, but the prognosis is still poor. PARP inhibitors like olaparib may improve glioblastoma outcomes. We implemented a phase 1-2a trial to assess the safety and efficacy of olaparib combined with standard radio-chemotherapy as a first-line treatment in unresected glioblastoma patients.
View Article and Find Full Text PDFClin Cancer Res
January 2025
Roswell Park Cancer Institute, Buffalo, NY, United States.
Background: Data in clear cell renal cell carcinoma (ccRCC) xenografts defined the seleno-L-methionine (SLM) dose and the plasma selenium concentrations associated with the enhancement of HIF1α/2α degradation, stabilization of tumor vasculature, enhanced drug delivery, and efficacy of axitinib. The data provided the rationale for the development of this phase I clinical trial of SLM and axitinib in advanced or metastatic relapsed ccRCC.
Patients And Methods: Patients were ≥18 years with histologically and radiologically confirmed advanced or metastatic ccRCC who had received at least one prior systemic therapy, which could include axitinib (last dose ≥6 months prior to enrollment).
JAMA Cardiol
January 2025
Ifakara Health Institute, Ifakara Branch, Ifakara, United Republic of Tanzania.
Importance: Hypertension is the primary cardiovascular risk factor in Africa. Recently revised World Health Organization guidelines recommend starting antihypertensive dual therapy; clinical efficacy and tolerability of low-dose triple combination remain unclear.
Objectives: To compare the effect of 3 treatment strategies on blood pressure control among persons with untreated hypertension in Africa.
The severity of COVID 19 symptoms has a direct correlation with lymphopenia, affecting natural killer (NK) cells. SARS-CoV-2 specific "memory" NK cells obtained from convalescent donors can be used as cell immunotherapy. In 2022 a phase I, dose-escalation, single center clinical trial was conducted to evaluate the safety and feasibility of the infusion of CD3/CD56 NK cells against moderate/severe cases of COVID-19 (NCT04578210).
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