Publications by authors named "Yong-Jiang Hei"
MET and its sole ligand, hepatocyte growth factor (HGF), are promising targets in gastric and gastroesophageal junction cancer. We evaluated whether MET protein expression or MET gene amplification is prognostic for overall survival (OS) in Chinese patients with advanced gastric or gastroesophageal junction cancer. Archival formalin-fixed, paraffin-embedded tumor samples from patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancer enrolled in clinical trials at Peking University Cancer Hospital from 2008 to 2010 were assessed for MET and phospho-MET (p-MET) expression by immunohistochemistry and MET amplification by FISH.
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- The study aimed to evaluate placental growth factor as a potential biomarker for predicting the effectiveness of motesanib in treating advanced nonsquamous non-small-cell lung cancer.
- In a phase 2 study, significant overall survival was observed in patients with a notable increase in placental growth factor after treatment, but these results did not translate into a phase 3 trial, which failed to find any survival benefit linked to the biomarker.
- The findings highlight difficulties in applying promising phase 2 biomarker findings to larger phase 3 trials successfully.
Article Synopsis
- The MONET1 phase 3 study assessed the effectiveness of motesanib combined with carboplatin/paclitaxel versus a placebo with the same chemotherapy for first-line treatment of advanced squamous non-small-cell lung cancer (NSCLC).
- Enrollment of patients with squamous histology was stopped due to increased early mortality and bleeding issues, while nonsquamous enrollment was temporarily paused and later resumed after protocol changes.
- The results showed that motesanib addition led to higher rates of serious adverse events compared to the placebo, with similar overall survival rates of approximately 11.1 months for the motesanib group and 10.7 months for the placebo group, indicating unacceptable toxicity.
Background: In patients with previously untreated metastatic colorectal cancer (mCRC), we conducted a phase 1b/randomized phase 2 trial to define the safety, tolerability, and efficacy of mFOLFOX6 plus bevacizumab (mFOLFOX6/bev) with conatumumab, an investigational, fully human monoclonal IgG1 antibody that specifically activates death receptor 5 (DR5).
Methods: Twelve patients were enrolled in a phase 1b open-label dose-escalation trial of conatumumab with mFOLFOX6/bev; thereafter, 190 patients were randomized 1:1:1 to receive mFOLFOX6/bev in combination with 2 mg/kg conatumumab, 10 mg/kg conatumumab, or placebo. Therapy cycles were repeated every 2 weeks until disease progression or the occurrence of unacceptable toxicity.
Article Synopsis
- Motesanib, a medication used for advanced cancers, has been linked to gallbladder toxicity, prompting a study on its effects on gallbladder size and function.
- In a trial involving 49 patients, treatment with motesanib led to an average increase in gallbladder volume and a decrease in function, with some patients experiencing gallbladder-related issues.
- Findings indicated that while motesanib caused some gallbladder complications, these effects appeared reversible after stopping the medication.
Introduction: This study evaluated the efficacy, safety, and pharmacokinetics of conatumumab combined with paclitaxel-carboplatin (PC) as first-line treatment for advanced non-small-cell lung cancer (NSCLC).
Methods: Patients (aged >18 years) with previously untreated advanced or recurrent NSCLC were randomized 1:1:1 (stratified by Eastern Cooperative Oncology Group performance status and disease stage) to receive up to six 3-week cycles of PC combined with conatumumab (arm 1, 3 mg/kg; arm 2, 15 mg/kg) or placebo (arm 3) every 3 weeks. The primary endpoint was progression-free survival (PFS).
Article Synopsis
- A study investigated if motesanib, an oral medication, combined with chemotherapy (carboplatin/paclitaxel) could enhance overall survival (OS) in patients with advanced nonsquamous non-small-cell lung cancer (NSCLC), especially those with adenocarcinoma.
- The results showed that while the median OS was slightly higher with motesanib (13.0 months) compared to placebo (11.0 months), the difference was not statistically significant, with a hazard ratio of 0.90 (P = .14).
- Additionally, motesanib treatment led to more adverse events, including higher instances of severe side effects, but did show improved progression-free survival (PFS) and objective response rate
Background: Conatumumab is a fully human monoclonal agonist antibody that binds to death receptor 5 and induces apoptosis in sensitive cells. This study evaluated the safety and efficacy of doxorubicin ± conatumumab as first-line systemic therapy for metastatic or locally advanced/unresectable soft-tissue sarcoma.
Methods: In Phase I, six patients received doxorubicin (75 mg/m2) with conatumumab (15 mg/kg) every 3 weeks.
Purpose: To evaluate the efficacy and safety of dulanermin combined with paclitaxel and carboplatin (PC) and bevacizumab (PCB) as first-line treatment for advanced or recurrent non-small-cell lung cancer (NSCLC).
Patients And Methods: Patients with squamous NSCLC and/or CNS metastases received PC every 3 weeks alone (arm 1) or with dulanermin 8 mg/kg for 5 days (arm 2). Patients with nonsquamous NSCLC received PCB alone (arm 3) or with dulanermin 8 mg/kg for 5 days (arm 4) or 20 mg/kg for 2 days (arm 5).
Background: The role of histology in the targeted management of nonsmall cell lung cancer (NSCLC) has garnered renewed attention in recent years. We provide contemporary population-based estimates of survival and an assessment of important prognostic factors in stage IV NSCLC by major histologic subtype.
Methods: Using data from the Surveillance, Epidemiology and End Results (SEER) Program, we stratified 51,749 incident stage IV NSCLC patients (1988-2003 with follow-up through 2006) by major histologic subtype.
Article Synopsis
- VEGF plays a key role in blood vessel growth and is a target for treating metastatic breast cancer; this study tested if motesanib, a VEGF receptor inhibitor, is more effective than placebo when paired with paclitaxel for HER2-negative breast cancer patients.
- The trial involved random assignments of patients to receive either motesanib, a placebo, or bevacizumab alongside paclitaxel, with the primary outcome being the objective response rate (ORR).
- Results showed no significant difference in ORR between the motesanib group (49%) and placebo group (41%), and both had similar adverse effects, with motesanib users experiencing more serious side effects like diarrhea and hypertension.*
Article Synopsis
- Antiangiogenic therapies, like motesanib, show promise for treating advanced thyroid cancer, but identifying which patients benefit most is challenging.
- An exploratory analysis of a phase 2 study found that changes in circulating biomarkers, particularly placental growth factor (PlGF) and soluble VEGF receptor 2, may predict tumor response and progression-free survival.
- Patients with significant increases in PlGF (4.7-fold) saw a much higher response rate (30%) compared to those with lower changes (3%), while those with lower baseline serum VEGF levels exhibited longer progression-free survival.
Objectives: Skeletal complications are a major cause of morbidity in men with hormone-refractory metastatic prostate cancer. These analyses were designed to identify the variables associated with a greater risk of skeletal complications.
Methods: The 643 subjects in this report were participants in a randomized placebo-controlled trial to evaluate the effects of zoledronic acid on the incidence of skeletal-related events.
Purpose: To evaluate the relative prognostic value for specific markers of osteoblast and osteoclast activity while controlling for previously reported prognostic variables among men with hormone-refractory metastatic prostate cancer.
Experimental Design: The 643 subjects in this report were participants in multicenter randomized controlled trial of zoledronic acid in men with metastatic prostate cancer. All subjects had bone metastases and disease progression despite medical or surgical castration.
Purpose: Three large, randomized trials of patients with bone metastases recently demonstrated that zoledronic acid reduces the risk of skeletal-related events. These trials provide an opportunity for investigating the correlation between bone metabolism and clinical outcome during bisphosphonate therapy.
Patients And Methods: Urinary measurements of N-telopeptide (Ntx) and serum bone alkaline phosphatase (BAP) were obtained in 1,824 bisphosphonate-treated patients-1,462 with zoledronic acid (breast, 490; prostate, 411; myeloma, 210; non-small-cell lung, 183; other, 168) and 362 with pamidronate (breast, 254; myeloma, 108).
Purpose: To describe the natural history of nonmetastatic prostate cancer and rising prostate-specific antigen (PSA) despite androgen deprivation therapy.
Patients And Methods: The 201 patients in this report were the placebo control group from an aborted randomized controlled trial to evaluate the effects of zoledronic acid on time to first bone metastasis in men with prostate cancer, no bone metastases, and rising PSA despite androgen deprivation therapy. Relationships between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses.
Background: Whether bone markers have prognostic value in patients with bone metastases is unknown. We investigated this question in patients with bone metastases secondary to prostate cancer and to non-small-cell lung cancer (NSCLC) and other solid tumors assigned to the placebo arms of two phase III trials of zoledronic acid.
Methods: Levels of the urinary bone resorption marker N-telopeptide and the serum bone formation marker bone-specific alkaline phosphatase were assessed every 3 months for patients with prostate cancer (n = 203) or NSCLC or other solid tumors (n = 238) and were categorized as low or high.
The results of a retrospective exploratory analysis of a phase III trial of zoledronic acid in patients with bone metastases secondary to lung cancer or other solid tumors are reported herein to assess the risk of skeletal-related events (SREs) and the efficacy of 4 mg zoledronic acid compared with placebo. The study is based on patient SRE history before study entry. Patients were stratified based on SRE history (eg, pathologic fracture, spinal cord compression, radiation therapy or surgery to bone, or hypercalcemia) before study entry, and SRE incidence over 21 months was analyzed.
View Article and Find Full Text PDFObjective: To investigate the usefulness of a novel retinoic acid receptor (RAR) antagonist (BMS-189453) in animal models of arthritis.
Methods: BMS-189453 was tested in HIG-82 rabbit synovial fibroblasts to determine its ability to repress collagenase (matrix metalloproteinase-1, MMP-1) mRNA expression in vitro. Cells were stimulated with phorbol myristate acetate or interleukin 1 beta and mRNA quantified by slot-blot analysis.