Abstract Background Few data on patterns of care and outcomes are available for elderly patients with diffuse large B-cell lymphoma (DLBCL) outside of clinical trials. Methods We identified patients ...with DLBCL older than 60 years from a regional cancer registry between 2000 and 2010. Based on registry data and chart review, 128 patients from the oncology network of Eastern Switzerland were analysed for patient characteristics, treatment and outcomes of DLBCL. Three age groups were compared: 60–69, 70–79 and over 80 years old. Results Median age was 73 years (range: 60 to 95 years). 52/121 treated patients received 6 cycles of R-CHOP/CHOP, of those 30 (58%), 18 (35%) and 4 (7%) patients were 60–69 years, 70–79 years or older than 80 years respectively, with a significant difference by age group, p = 0.001. Median OS of patients 60–69, 70–79, and 80 years and older receiving 6 cycles of R-CHOP/CHOP were: 54 months, 31 months and 24 months respectively. In comparison, patients receiving other than 6 cycles of R-CHOP/CHOP treatment regimens had a median OS of 22 months, 17 months and 6 months, respectively. In the multivariable analysis other than 6 cycles of R-CHOP/CHOP were significantly associated with poor survival. The risk of dying increased by a mean of 6% for each year of age from age 60 years onwards. Conclusion In conclusion, treatment regimens other than 6 cycles of R-CHOP/CHOP were significant predictors for survival in our oncology network. The possibility of using R-CHOP treatment regimen should be seriously considered in elderly patients with DLBCL.
This phase I trial was designed to develop a new effective and well-tolerated regimen for patients with aggressive B cell lymphoma not eligible for front-line anthracycline-based chemotherapy or ...aggressive second-line treatment strategies. The combination of rituximab (375 mg/m
2
on day 1), bendamustine (70 mg/m
2
on days 1 and 2), and lenalidomide was tested with a dose escalation of lenalidomide at three dose levels (10, 15, or 20 mg/day) using a 3 + 3 design. Courses were repeated every 4 weeks. The recommended dose was defined as one level below the dose level identifying ≥2/6 patients with a dose-limiting toxicity (DLT) during the first cycle. Thirteen patients were eligible for analysis. Median age was 77 years. WHO performance status was 0 or 1 in 12 patients. The Charlson Comorbidity Index showed relevant comorbidities in all patients. Two DLTs occurred at the second dose level (15 mg/day) within the first cycle: one patient had prolonged grade 3 neutropenia, and one patient experienced grade 4 cardiac adverse event (myocardial infarction). Additional grade 3 and 4 toxicities were as follows: neutropenia (31 %), thrombocytopenia (23 %), cardiac toxicity (31 %), fatigue (15 %), and rash (15 %). The dose of lenalidomide of 10 mg/day was recommended for a subsequent phase II in combination with rituximab 375 mg/m
2
on day 1 and bendamustine 70 mg/m
2
on days 1 and 2.
BACKGROUND: Low-energy fractures of the hip, forearm, shoulder, and spine are known consequences of osteoporosis. OBJECTIVE: We evaluated the effect of 1 y of treatment with calcium and vitamin D on ...bone mineral density (BMD) and bone markers in patients with a recent low-energy fracture. DESIGN: In a double-blinded design, patients with fracture of the hip (lower-extremity fracture, or LEF) or upper extremity (UEF) were randomly assigned to receive 3000 mg calcium carbonate + 1400 IU cholecalciferol or placebo (200 IU cholecalciferol). BMD of the hip (HBMD) and lumbar spine (LBMD) were evaluated by dual-energy X-ray absorptiometry, and physical performance was assessed by the timed Up & Go test. Serum concentrations of 25-hydroxycholecalciferol, parathyroid hormone (PTH), telepeptide of type I collagen (ICTP), osteocalcin, and N-terminal propeptide of collagen type I were measured. RESULTS: A total of 122 patients were included (84% women; x ± SD age: 70 ± 11 y); 68% completed the study. In an intention-to-treat analysis, LBMD increased in the intervention group and decreased in the placebo group, and the difference between the groups was significant after 12 mo: 0.931 ± 0.211 compared with 0.848 ± 0.194 (P < 0.05). No significant change was shown for HBMD. The effect of treatment was more pronounced in patients aged <70 y. The intervention decreased bone turnover. PTH was significantly lower in the intervention group (P < 0.01) for the LEF patients. ICTP and change in LBMD were significantly related to physical performance. CONCLUSIONS: A 1-y intervention with calcium and vitamin D reduced bone turnover, significantly increased BMD in patients younger than 70 y, and decreased bone loss in older patients. The effect of treatment was related to physical performance.
ABSTRACT
Background
Vitamin K deficiency is highly prevalent in patients on dialysis and may contribute to their low bone mineral density (BMD) and increased risk of fracture. This study investigated ...the effect of menaquinone-7 (MK-7) supplementation on BMD in patients on chronic dialysis.
Methods
In a multicentre, double-blind, placebo-controlled intervention trial, 123 patients on chronic dialysis were randomised to a daily oral supplement of either MK-7 360 µg or placebo for 2 years. BMD of the distal radius (1/3, mid, ultradistal and total), femoral neck, lumbar spine (L1–L4) and whole body was assessed by dual-energy X-ray absorptiometry. Serum levels of vitamin K1 and MK-7 and plasma levels of total osteocalcin, dephosphorylated-uncarboxylated matrix Gla protein and protein induced by vitamin K absence II were measured to assess vitamin K status.
Results
After 2 years, an accelerated BMD loss of the 1/3 distal radius was found with MK-7 supplementation {mean difference of changes relative to placebo −0.023 g/cm2 95% confidence interval (CI) −0.039 to −0.008}, whereas the decrease in lumbar spine BMD seen in the placebo group was prevented mean difference of changes between groups 0.050 g/cm2 (95% CI 0.015–0.085). No significant effects were observed at the remaining skeletal sites. Vitamin K status strongly improved in MK-7-supplemented participants.
Conclusion
Compared with placebo, an accelerated BMD loss of the 1/3 distal radius was found after 2 years of MK-7 supplementation, whereas a decline in lumbar spine BMD was prevented. As such, MK-7 supplementation might modify BMD site-specifically in patients on dialysis. In aggregate, our findings do not support MK-7 supplementation to preserve bone in patients on dialysis.
Graphical Abstract
Graphical Abstract
Purpose
We assessed the impact of hepatic dysfunction on the safety and pharmacology of gemcitabine/capecitabine in patients with advanced pancreatico-biliary cancer.
Methods
We included 12 patients ...receiving 3 weekly gemcitabine 1,000 mg/m
2
day 1, 8 and oral capecitabine 650 mg/m
2
b.i.d. over 2 weeks until disease progression or intolerable toxicity. Patients were included into one normal hepatic function cohort total bilirubin (TB) ≤15 μmol/L and 3 cohorts with increasing TB (16–39, 40–80, >80 μmol/L). Three patients with a creatinine clearance <60 ml/min were also included. Patients were sampled for gemcitabine, difluoro-deoxy uridine, intracellular gemcitabine triphosphates, capecitabine, 5′-deoxy-5-fluorocytidine, 5′-deoxy-5-fluorouridine and 5-fluorouracil up to 4 h after initiation of chemotherapy on day 1, and up to 90 min on day 8. All compounds were analyzed using validated liquid chromatography–tandem mass spectrometry. Nonlinear mixed-effect modeling was used for population analysis.
Results
Hepatic dysfunction was caused by intrahepatic cholestasis in 4 out of 8 patients (50 %) and extrahepatic cholestasis in another 4 patients (50 %). Dose-limiting toxicity was increasing hyperbilirubinemia and severe neutropenia in 2 patients each. Hepatic dysfunction was not associated with dose-limiting toxicity or severe hematological or non-hematological toxicity. However, hepatic dysfunction was associated with low clearance of both gemcitabine (
p
= 10
−3
) and capecitabine (
p
= 10
−5
), and low intracellular gemcitabine triphosphate concentrations (
p
= 10
−3
).
Conclusions
Gemcitabine/capecitabine can be given at the standard dose in patients with severe hyperbilirubinemia, though the present data suggest that gemcitabine’s activity may be limited due to poor intracellular activation. In patients with severe hyperbilirubinemia, initial monotherapy with capecitabine should be considered, followed by the addition of gemcitabine with improving hyperbilirubinemia.
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