5 research outputs found
The urgent need for integrated science to fight COVID-19 pandemic and beyond
The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health
concern is not only a medical problem, but also afects society as a whole; so, it has also become the leading scientifc
concern. We discuss in this treatise the importance of bringing the worldās scientists together to fnd efective soluā
tions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to
manage the pandemicās consequences and prevent recurrences of similar pandemics
A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma
Background: Protein kinase C beta (PKCĪ²), a pivotal enzyme in B-cell signaling and survival, is overexpressed in most cases of mantle cell lymphoma (MCL). Activation of PI3K/AKT pathway is involved in pathogenesis of MCL. Enzastaurin, an oral serine/threonine kinase inhibitor, suppresses signaling through PKCĪ²/PI3K/AKT pathways, induces apoptosis, reduces proliferation, and suppresses tumor-induced angiogenesis. Patients and methods: Patients with relapsed/refractory MCL, and no more than four regimens of prior therapy, received 500 mg enzastaurin, orally, once daily. Results: Sixty patients, median age 66 years (range 45-85), Eastern Cooperative Oncology Group performance status of zero to two (48% had baseline International Prognostic Index of 3-5), were enrolled. Most patients had prior CHOP-like chemotherapy and/or rituximab (median = 2 regimens). No drug-related deaths occurred. There was one case each of grade 3 anemia, diarrhea, dyspnea, vomiting, hypotension, and syncope. Fatigue was the most common toxicity. Although no objective tumor responses occurred, 22 patients (37%, 95% CI 25% to 49%) were free from progression (FFP) for ā„3 cycles (one cycle = 28 days); 6 of 22 were FFP for >6 months. Two patients remain on treatment and FFP at >23 months. Conclusion: Freedom from progression for >6 months in six patients and a favorable toxicity profile with minimal hematological toxicity indicate that enzastaurin warrants evaluation as maintenance therapy and combination chemotherapy in MCL
Immunochemotherapy With Obinutuzumab or Rituximab for Previously Untreated Follicular Lymphoma in the GALLIUM Study: Influence of Chemotherapy on Efficacy and Safety
Purpose;
The GALLIUM study (ClinicalTrials.gov identifier: NCT01332968) showed that obinutuzumab
(GA101; G) significantly prolonged progression-free survival (PFS) in previously untreated patients
with follicular lymphoma relative to rituximab (R) when combined with cyclophosphamide (C),
doxorubicin, vincristine (V), and prednisone (P; CHOP); CVP; or bendamustine. This report focuses
on the impact of chemotherapy backbone on efficacy and safety.
Patients and Methods:
A total of 1,202 patients with previously untreated follicular lymphoma (grades 1 to 3a), advanced
disease (stage III or IV, or stage II with tumor diameter $ 7 cm), Eastern Cooperative Oncology
Group performance status 0 to 2, and requiring treatment were randomly assigned 1:1 to G
1,000 mg on days 1, 8, and 15 of cycle 1 and day 1 of subsequent cycles or R 375 mg/m2 on day 1 of
each cycle, for six to eight cycles, depending on chemotherapy (allocated nonrandomly by center).
Responding patients received G or R for 2 years or until disease progression.
Results:
Baseline Follicular Lymphoma International Prognostic Index risk, bulky disease, and comorbidities differed
by chemotherapy. After 41.1 months median follow-up, PFS (primary end point) was superior for G plus
chemotherapy (overall hazard ratio [HR], 0.68; 95% CI, 0.54 to 0.87; P= .0016), with consistent results across
chemotherapy backbones (bendamustine: HR, 0.63; 95% CI, 0.46 to 0.88; CHOP: HR, 0.72; 95% CI, 0.48 to
1.10; CVP: HR, 0.79; 95% CI, 0.42 to 1.47). Grade 3 to 5 adverse events, notably cytopenias, were most
frequent with CHOP. Grade 3 to 5 infections and second neoplasms were most frequent with bendamustine, which was associated with marked and prolonged reductions in T-cell counts. Fatal events were
more frequent in patients treated with bendamustine, possibly reflecting differences in patient risk profiles.
Conclusion:
Improved PFS was observed for G plus chemotherapy for all three chemotherapy backbones. Safety
profiles differed, although comparisons are confounded by nonrandom chemotherapy allocation
The urgent need for integrated science to fight COVID-19 pandemic and beyond
The COVID-19 pandemic has become the leading societal concern. The pandemic has shown that the public health
concern is not only a medical problem, but also afects society as a whole; so, it has also become the leading scientifc
concern. We discuss in this treatise the importance of bringing the worldās scientists together to fnd efective soluā
tions for controlling the pandemic. By applying novel research frameworks, interdisciplinary collaboration promises to
manage the pandemicās consequences and prevent recurrences of similar pandemics