Arsenic trioxide in patients with hepatocellular carcinoma: A phase II trial

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14129-14129 ◽  
Author(s):  
C. Lin ◽  
C. Hsu ◽  
C. Hsu ◽  
W. Hsu ◽  
A. Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Arsenic Trioxide ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Locally Advanced ◽  
Dose Schedule ◽  
Advanced Hcc ◽  
Kaplan Meier ◽  
Disease Stabilization

14129 Background: Arsenic trioxide induces growth inhibition and apoptosis in human hepatocellular carcinoma (HCC) cell lines. A phase II trial was conducted to evaluate the efficacy and toxicity of single-agent arsenic trioxide in patients with HCC. Methods: Inclusion criteria included advanced HCC patients to whom no standard palliative treatment can be offered, good organ function and liver function reserve. Patients received arsenic trioxide 0.16–0.24 mg/kg/day for 5–6 days per week for 3–4 weeks followed by one-week rest. Tumor response was accessed every 2 months. Primary endpoint was percentage of patients with 6-month disease stabilization. Results: Twenty-nine patients (M/F = 24:5; median age: 59) with locally advanced or metastatic HCC received a total of 61 cycles (median, 2; range, 1–6). One patient had partial remission. Three patients had disease stabilization for at least six months. The 6-month tumor stabilization rate was 14% (95% CI, 1–27). The median overall survival was 4.8 months (95% CI, 1.4–8.2) and one-year survival estimated by Kaplan-Meier methodology was 30%. Conclusions: Single-agent arsenic trioxide using this dose schedule is not active against advanced HCC patients. No significant financial relationships to disclose.

scholarly journals Gemcitabine Plus Carboplatin in Patients with Advanced Hepatocellular Carcinoma: Results of a Phase II Study

ISRN Oncology ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-5
Author(s):  
Aly M. Azmy ◽  
Khalid E. Nasr ◽  
Nagy S. Gobran ◽  
M. Yassin
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Phase Ii Study ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Stage ◽  
Survival Times ◽  
Advanced Hcc ◽  
Disease Stabilization ◽  
Grade 3

Objectives. Assessment of gemcitabine/carboplatin combination in patients with advanced-stage hepatocellular carcinoma (HCC) in a phase II trial for safety and efficacy. Methods. Forty patients with previously untreated advanced-stage HCC were prospectively enrolled and subjected to gemcitabine/carboplatin regimen which consisted of gemcitabine 1000 mg/m2 on days 1 and 8, and carboplatin AUC 6 on day 1. The treatment was repeated every 3 weeks until disease progression or limiting toxicity. Results. Forty patients were assessable for efficacy and toxicity. In all, 276 treatment cycles were administered. No toxic deaths occurred. Hematological grade 3-4 toxicity consisted of thrombocytopenia (27% of patients) and neutropenia (24%), including 2 febrile neutropenia and anemia (9%). Grade 3 carboplatin-induced neurotoxicity was observed in 3 (9%) patients. ORR was 23% (95% CI, 0.10–0.29) with 9 partial responses and disease stabilization was observed in 46% (95% CI, 0.22–0.42) of patients, giving a disease control rate of 69%. Median progression-free and overall survival times were, respectively, 5 months (95% CI: 3–8 months) and 8 months (95% CI: 6–18 months). Conclusion. The gemcitabine/carboplatin regimen seems to be effective, well tolerated, and active in advanced HCC.

scholarly journals Phase II Study of the Mitogen-Activated Protein Kinase 1/2 Inhibitor Selumetinib in Patients With Advanced Hepatocellular Carcinoma

2011 ◽  
Vol 29 (17) ◽  
pp. 2350-2356 ◽  
Author(s):  
Bert H. O'Neil ◽  
Laura W. Goff ◽  
John Sae Wook Kauh ◽  
Jonathan R. Strosberg ◽  
Tanios S. Bekaii-Saab ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Kinase ◽  
Phase Ii ◽  
Systemic Therapy ◽  
Single Agent ◽  
Locally Advanced ◽  
Mitogen Activated Protein Kinase ◽  
Advanced Hepatocellular Carcinoma ◽  
Time To Progression ◽  
Mitogen Activated Protein

Purpose Hepatocellular carcinoma (HCC) is a common and deadly malignancy with few systemic therapy options. The RAF/mitogen-activated protein kinase kinase (MEK)/extracellular signal-related kinase (ERK) pathway is activated in approximately 50% to 60% of HCCs and represents a potential target for therapy. Selumetinib is an orally available inhibitor of MEK tyrosine kinase activity. Patients and Methods Patients with locally advanced or metastatic HCC who had not been treated with prior systemic therapy were enrolled on to the study. Patients were treated with selumetinib at its recommended phase II dose of 100 mg twice per day continuously. Cycle length was 21 days. Imaging was performed every two cycles. Biopsies were obtained at baseline and at steady-state in a subset of patients, and pharmacokinetic (PK) analysis was performed on all patients. Results Nineteen patients were enrolled, 17 of whom were evaluable for response. Most (82%) had Child-Pugh A cirrhosis. Toxicity was in line with other studies of selumetinib in noncirrhotic patients. PK parameters were also comparable to those in noncirrhotic patients. No radiographic response was observed in this group, and the study was stopped at the interim analysis. Of 11 patients with elevated α-fetoprotein, three (27%) had decreases of 50% or more. Median time to progression was 8 weeks. Inhibition of ERK phosphorylation was demonstrated by Western blotting. Conclusion In this study of selumetinib for patients with HCC, no radiographic responses were seen and time to progression was short, which suggests minimal single-agent activity despite evidence of suppression of target activation.

Arsenic trioxide in patients with hepatocellular carcinoma: a phase II trial

2006 ◽  
Vol 25 (1) ◽  
pp. 77-84 ◽  
Author(s):  
Chia-Chi Lin ◽  
Chiun Hsu ◽  
Chih-Hung Hsu ◽  
Wei-Ling Hsu ◽  
Ann-Lii Cheng ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Arsenic Trioxide ◽  
Phase Ii ◽  
Phase Ii Trial

A phase II trial of perifosine in patients with advanced renal cell carcinoma (RCC) who have failed tyrosine kinase inhibitors (TKI)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5101-5101 ◽  
Author(s):  
D. C. Cho ◽  
R. A. Figlin ◽  
K. T. Flaherty ◽  
D. Michaelson ◽  
J. A. Sosman ◽  
...  
Keyword(s):  
Phase Ii ◽  
Kinase Inhibitors ◽  
Phase Ii Trial ◽  
Single Agent ◽  
Progression Free Survival ◽  
Normal Organ ◽  
Disease Stabilization ◽  
Previously Treated ◽  
Map Kinase Pathway ◽  
Ecog Ps

5101 Background: The recently demonstrated activity of inhibitors of TORC1 in RCC has raised the possibility that even greater effects may be achieved by targeting upstream of this pathway. Perifosine is a synthetic alkylphospholipid which inhibits Akt activity and also has cell-dependent effects upon the MAP-kinase pathway. Prior single-agent trials showed disease stabilization/regression in patients (pts) with advanced RCC; however, few pts were previously treated with a TKI. Therefore, we conducted a multi-center phase II trial to determine the safety and efficacy of perifosine in pts with advanced RCC refractory to VEGFR TKI. Methods: Primary objectives were to measure the % of pts progression-free at 12 weeks (wks) and overall progression-free survival (PFS) of perifosine (100 mg qhs). Secondary objectives included overall response rate (> PR), and safety, Eligibility: ECOG PS 0–1, pts with metastatic RCC who have RECIST defined progression on either sunitinib or sorafenib. Prior Rx with immunotherapy and bevacizumab was permitted. Normal organ and marrow function required. Results: From 4/07–10/08, 24 pts were treated at four sites. Median age 67 (range 47–78) and 16 were male; 90% of pts had predominantly clear cell histology. Prior sunitinib = 12; prior sorafenib = 12 (1.5 avg prior Rx). As of 12/08, all 24 pts were evaluable for PFS, response and toxicity as follows in the table . 6/24 pts remain on treatment (range 7 - 84 wks). Therapy was well tolerated with primarily Grade (G) 1 & 2 adverse events. G 3 & 4 events were: dyspnea (8%), hyponatremia (8%), pulmonary embolism (4%) and arthalgia (4%). Conclusions: Perifosine has promising activity in pts with RCC who have failed prior TKI therapy. The favorable toxicity profile suggests potential for combinational therapies with VEGF-targeted agents. Additional studies are under consideration to evaluate perifosine for clinical benefit in pts with previously treated RCC. [Table: see text] [Table: see text]

Phase II Trial of Weekly Paclitaxel for Unresectable Angiosarcoma: The ANGIOTAX Study

2008 ◽  
Vol 26 (32) ◽  
pp. 5269-5274 ◽  
Author(s):  
Nicolas Penel ◽  
Binh Nguyen Bui ◽  
Jacques-Olivier Bay ◽  
Didier Cupissol ◽  
Isabelle Ray-Coquard ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Locally Advanced ◽  
Survival Rates ◽  
Progression Free Survival ◽  
Dose Schedule ◽  
Weekly Paclitaxel ◽  
Curative Intent ◽  
Free Survival ◽  
Grade 3

Purpose The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma. Patients and Methods Thirty patients were entered onto the study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m2 on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles. Results The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naïve patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic death occurred as a result of a thrombocytopenia episode. Six patients presented with grade 3 toxicities and one patient presented with a grade 4 toxicity. Anemia and fatigue were the most frequently reported toxicities. Conclusion Weekly paclitaxel at the dose schedule used in the current study was well tolerated and demonstrated clinical benefit.

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