Midostaurin in patients with acute myeloid leukemia and FLT3-TKD mutations: a subanalysis from the RATIFY trial.

The results from the RATIFY trial (ClinicalTrials.gov: NCT00651261; CALGB 10603) showed that midostaurin combined with standard chemotherapy significantly improved outcomes in patients with FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML), compared with placebo. In this post hoc subgroup analysis from the trial, we evaluated the impact of midostaurin in 163 patients with FLT3-tyrosine kinase domain (TKD) mutations.

Switching patients with acromegaly from octreotide to pasireotide improves biochemical control: crossover extension to a randomized, double-blind, Phase III study.

Background: Many patients with acromegaly do not achieve biochemical control with first-generation somatostatin analogues. A large, multicenter, randomized, Phase III core study demonstrated that pasireotide LAR had significantly superior efficacy over octreotide LAR. This analysis explores the efficacy and safety of switching therapeutic arms in inadequately controlled patients during a 12-month crossover extension.

Pasireotide LAR maintains inhibition of GH and IGF-1 in patients with acromegaly for up to 25 months: results from the blinded extension phase of a randomized, double-blind, multicenter, Phase III study.

Purpose: A large, randomized, double-blind, Phase III core study demonstrated that pasireotide LAR was significantly superior to octreotide LAR at providing GH <2.5 μg/L and normalized IGF-1 after 12 months' treatment in patients with acromegaly. We report the efficacy and safety of pasireotide LAR and octreotide LAR after up to 26 months' treatment.

Treatment of bone metastases before the onset of pain.

Purpose: Bone metastases are often asymptomatic and are not diagnosed until after the onset of bone pain. However, bone structural integrity may have diminished considerably before pain onset, resulting in increased risk of skeletal-related events. Therefore, we evaluated whether bisphosphonate therapy was differentially beneficial depending on initiation before or after the onset of bone pain.

Disease progression increases the risk of skeletal-related events in patients with bone metastases from castration-resistant prostate cancer, lung cancer, or other solid tumors.

Baseline and disease progression characteristics may predict the risk of skeletal-related events (SREs) in patients with bone metastases from various solid tumors. Exploratory analysis of phase III trials compared zoledronic acid with placebo in patients with bone metastases from castration-resistant prostate cancer (N = 643) and lung cancer or other solid tumors (N = 773), adjusted for baseline and time-dependent disease parameters. In all models, more than three bone lesions at baseline correlated with the increased SRE risk.

Continuing benefit of zoledronic acid in preventing skeletal complications in patients with bone metastases.

Purpose: We previously reported the efficacy of zoledronic acid 4 mg versus placebo (every 3 weeks for 24 months) for the prevention of skeletal-related events (SREs) in men with advanced prostate cancer and bone metastases. We conducted several retrospective exploratory analyses to determine whether zoledronic acid has continuing efficacy during long-term treatment.

Patients And Methods: This report included analysis of the occurrence of SREs during the extension phase only (months 16-24), analysis of skeletal complications excluding the first SRE at 15 months (core phase), and stratified analysis of patients by history of SREs before study entry.

Pathologic fractures correlate with reduced survival in patients with malignant bone disease.

Background: Data from randomized, controlled trials of zoledronic acid were retrospectively analyzed to assess the effect of pathologic fractures on survival in patients with malignant bone disease.

Methods: A Cox regression model was used to estimate the effect of fractures (time-dependent variable) on survival in patients with stage III multiple myeloma or bone metastases from solid tumors enrolled in 3 large trials. Patients were randomized to receive zoledronic acid, pamidronate, or placebo every 3-4 weeks for up to 24 months (prostate cancer, breast cancer, and multiple myeloma) or up to 21 months (lung and other solid tumors).

Capecitabine plus paclitaxel as front-line combination therapy for metastatic breast cancer: a multicenter phase II study.

Purpose: The goal of this multicenter, open-label phase II study was the clinical evaluation of combination therapy with the oral fluoropyrimidine capecitabine and the taxane paclitaxel in patients with metastatic breast cancer (MBC).

Patients And Methods: Forty-seven patients with MBC received oral capecitabine at 1650 mg/m(2)/d (825 mg/m(2) twice daily) on days 1 through 14, and intravenous infusion of paclitaxel at 175 mg/m(2) on day 1 of each 21-day treatment cycle. Treatment continued until disease progression, intolerable toxicity, or patient' s decision to discontinue.

Phase II study of oral capecitabine in patients with advanced or metastatic pancreatic cancer.

Purpose: To determine the safety and efficacy of capecitabine (Xeloda; Roche Laboratories, Nutley, NJ) in patients with metastatic or unresectable, locally advanced pancreatic cancer.

Patients And Methods: Forty-two patients were treated with oral capecitabine 1,250 mg/m(2) administered twice daily (2,500 mg/m(2)/d) as intermittent therapy in 3-week cycles consisting of 2 weeks of treatment followed by 1 week without treatment. Tumor lesions were assessed by computed tomography scan or physical examination at 6-week intervals (after every two cycles).