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.

Phase II study of intrabuccally-administered amplitude-modulated electromagnetic fields in patients with advanced hepatocellular carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e15573-e15573
Author(s):  
F. P. Costa ◽  
A. C. de Oliveira ◽  
R. Meirelles ◽  
M. M. Machado ◽  
R. Surjan ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Electromagnetic Fields ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Hepatic Function ◽  
Advanced Hepatocellular Carcinoma ◽  
Free Survival ◽  
Advanced Hcc ◽  
Independent Review

e15573 Background: Over the past few years we have identified tumor-specific frequencies for several common forms of cancer. The goal of this study was to assess the tolerability and effectiveness of electromagnetic fields amplitude-modulated at tumor-specific frequencies and administered by means of an intrabuccal spoon-shaped probe in patients with advanced hepatocellular carcinoma (HCC). Methods: From October 2005 to July 2007, patients with advanced HCC and Child-Pugh A or B were recruited in a phase II study. Three daily 60 min outpatient treatments were administered until disease progression or death. Imaging studies were performed every eight weeks. The primary efficacy end point was progression-free survival ≥ 6 months. Secondary efficacy end points were progression-free survival and overall survival. Results: A total of 41 patients were enrolled, 17 had Child-Pugh A, 20 Child-Pugh B disease. The median age was 64.0 years. Seventeen patients (34.1%) were progression-free for more than 6 months. Median progression-free and overall survivals were 4.8 months (95% CI 2.3–6.0) and 6.9 months (95 CI 4.8–11.1). As of December 2008, four patients are alive and two patients, who are still undergoing therapy, remain progression-free for 30.4 and 30.7 months, respectively. Four patients had partial response (9.8%) and sixteen had stable disease for at least 12 weeks (39.0%) according to the RECIST criteria resulting in 48.8% disease control. All responses were confirmed by independent review. There were no NCI grade 2, 3 or 4 toxicities. One patient developed grade 1 mucositis and one patient grade 1 fatigue. Conclusions: In patients with advanced HCC and impaired hepatic function, treatment with amplitude-modulated electromagnetic fields is safe, well tolerated, and shows evidence of anti-tumor effects, which are long-lasting in some patients. No significant financial relationships to disclose.

Phase II trial of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma (HCC).

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 240-240 ◽  
Author(s):  
Aiwu Ruth He ◽  
Anteneh Tesfaye ◽  
Daniel Smith ◽  
John Marshall ◽  
Michael J. Pishvaian ◽  
...  
Keyword(s):  
Dna Repair ◽  
Disease Progression ◽  
Cancer Progression ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Common Grade ◽  
Grade 3

240 Background: The combination of the imidazotetrazine derivative temozolomide (TMZ) and poly(ADP-ribose) polymerase inhibitor veliparib (ABT-888) has shown in vivo activity against a variety of tumor types through the alkylating effects of TMZ and DNA repair inhibition by ABT-888. To date, no studies have examined the combination of TMZ and ABT-888 in treating advanced HCC refractory to sorafenib. Methods: This is a single arm Phase II trial. Eligible HCC patients have Child Pugh A/B cirrhosis and have failed prior treatment with sorafenib either through intolerance or disease progression. All patients have received ABT-888 40 mg daily on days 1-7 and Temozolomide 150 mg/m2 daily on days 1-5 in 28 day cycles for a maximum of 6 cycles. Tumor response is analyzed every 2 cycles using RECIST criteria. The primary endpoint is time to disease progression. The trial is being conducted using a modified Simon’s two-stage design optimal design as implemented by Hanfelt, et al. Results: The trial is currently in Simon Stage 1 with 16 patients recruited: 9 patients have stopped the study due to disease progression, 3 patients are still on protocol, and 4 patients stopped the study for reasons other than disease progression. 7 patients had disease progression at two months, 1 patient had cancer progression at 4 months, and 1 patient had disease progression at 16 months. Median time to progression in these 9 patients was 56 days (range 42-486 days). The four patients that stopped the study prematurely were for the following reasons: hiccups/dehydration, Mallory-Weiss tear secondary to refractory nausea, intraperitoneal bleeding from exophytic HCC lesion, and development of hepatorenal syndrome in a paracentesis-dependent patient. The most common grade 3 toxicities in this cohort so far have been nausea/vomiting (in 2 subjects), and anemia/thrombocytopenia (in 2 subjects). Defects in DNA repair pathways are being tested from the liver biopsy in the patient who had response to TMZ and ABT-888 for 16 months. Conclusions: The combination of TMZ and ABT-888 is fairly tolerated in patients with advanced HCC. So far, the treatment did not show activities in majority of patients with advanced HCC. Clinical trial information: NCT01205828.

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.

Clinical, pharmacodynamic (PD), and pharmacokinetic (PK) evaluation of cediranib in advanced hepatocellular carcinoma (HCC): A phase II study (CTEP 7147).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 4112-4112 ◽  
Author(s):  
Andrew X. Zhu ◽  
Marek Ancukiewicz ◽  
Jeffrey G. Supko ◽  
Lawrence Scott Blaszkowsky ◽  
Jeffrey A. Meyerhardt ◽  
...  
Keyword(s):  
Steady State ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Vegf Receptor ◽  
Advanced Hepatocellular Carcinoma ◽  
Eligibility Criteria ◽  
Advanced Hcc ◽  
Baseline Levels ◽  
Grade 3

4112 Background: Sorafenib remains the only approved systemic therapy in HCC. We performed a phase II study of cediranib (AZD2171)—a more potent and selective pan-VEGF receptor inhibitor—in advanced HCC patients (pts). Methods: Eligibility criteria included unresectable or metastatic measurable HCC, ECOG PS ≤2, CLIP score ≤3, and adequate organ function. Patients received cediranib at 30 mg po qd continuously (4-wk cycle). The primary endpoint was progression free survival (PFS). We also assessed overall survival (OS) and response rates, steady-state PK of cediranib, and blood circulating biomarkers. Results: Since 6/16/09, we have enrolled the targeted 17 pts required for the first stage of the planned study: ECOG 0/1/2=5/11/1, CLIP 1/2/3=6/4/7, Child A/B=14/3, BCLC C=17. Nine pts had prior sorafenib. The best response was stable disease in five pts (29%). The median PFS was 5.3 months (95% CI: 3.5-9.7). The median OS was 11.7 months (95% CI: 7.5-13.6). Grade 3 toxicities included hypertension (29%), hyponatremia (12%), elevated SGOT (12%) and one pt each (6%) in SGPT, fatigue, hyperbilirubinemia, cardiac ischemia, and proteinuria. Grade 4 pulmonary embolism and brainstem hemorrhage occurred in 1 pt each. Steady-state PK parameters (mean±SD) were, Cmin, 22±21 ng/mL; Cmax, 55±33 ng/mL; AUCτ, 887±503 ng*h/mL. Plasma levels of VEGF and PlGF increased and sVEGFR1, sVEGFR2 and Ang-2 decreased significantly after cediranib treatment (p<0.05). PFS was inversely correlated with baseline levels of bFGF, sVEGFR2 and VEGF, and OS was inversely correlated with baseline levels of sVEGFR1, Ang-2, TNF-alpha and CD34+CD133+ hematopoietic progenitor cells (p<0.05). Conclusions: Cediranib at 30 mg daily is associated with high frequency of grade 3 hypertension and shows preliminary evidence of antitumor activity in advanced HCC pts. Exploratory studies confirmed potential PD and response biomarkers of anti-VEGF therapy. Cediranib exhibits similar PK in HCC pts as in those with other tumor types and normal/near normal hepatic function. This study was stopped by AstraZeneca after discontinuation of cediranib development for unrelated factors.

Rapamycin in patients with advanced hepatocellular carcinoma progressing on prior antiangiogenic therapy.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 356-356
Author(s):  
Mohamed Bouattour ◽  
Johanna Wassermann ◽  
Chantal Dreyer ◽  
Valérie Vilgrain ◽  
Valerie Paradis ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Stable Disease ◽  
Tumor Response ◽  
Antiangiogenic Therapy ◽  
Mtor Inhibitors ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Disease Stabilization ◽  
Heavily Pretreated ◽  
Grade 3

356 Background: PI3K/Akt/mTOR is a critical survival pathway in hepatocellular carcinoma (HCC) often correlated with poor prognosis. Rapamycin (sirolimus) and its analogue everolimus, are specific mTOR inhibitors that showed promising antitumor activity in preclinical models and clinical cases of HCC Aims: To evaluate the safety and efficacy of rapamycin in patients (pts) with advanced HCC after failure or intolerance to prior antiangiogenic therapy Methods: In this retrospective cohort, we analyzed consecutive patients with progressive HCC after 1 to 3 lines of treatment including at least sorafenib. All pts received oral rapamycin at 20 to 30 mg once a week. Adverse events (AEs) were assessed using NCI-CTCAE v3.0, and tumor response was evaluated according to RECIST criteria. Results: Nine patients (F/M: 1/8) with compensated liver cirrhosis (Child A, n = 6; Child B7, n = 2) or no cirrhosis (n=1) and histologically proven HCC were included in this study. Overall, therapy with rapamycin was well tolerated. Most common toxicities were asthenia (grade 1-2: 5 pts) anaemia (all grade: 5 pts; grade 3: 2 pts ) and thrombocytopenia (grade 1-2: 2 pts). Liver function deterioration was observed in 2 pts with advanced cirrhosis (Child B7). Radiological evaluation was available in 6 pts. No objective tumor response was observed however stable disease ≥ 3 months was observed in 4 cases. Moreover, 2 pts showed stable disease at 6 months. Prolonged stabilization under rapamycin was observed in pts who were previously controlled at least for 6 months with sorafenib. Rapamycin was discontinued due to disease progression in 7/8 pts, toxicity in 1/8 pts. One pt shows ongoing long-lasting disease stabilization (8 + months). Conclusions: Rapamycin displayed an acceptable safety profile and may achieved disease stabilization in patients with heavily pretreated advanced HCC.

Final phase Ib data for the oral c-Met inhibitor tepotinib in patients with previously treated advanced hepatocellular carcinoma.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e15676-e15676 ◽  
Author(s):  
Sandrine J. Faivre ◽  
Jean-Frédéric Blanc ◽  
Philippe Merle ◽  
Angelica Fasolo ◽  
Angelo Iacobellis ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Tumor Size ◽  
Advanced Hepatocellular Carcinoma ◽  
First Line ◽  
Phase Ib ◽  
Advanced Hcc ◽  
Peripheral Edema ◽  
Met Inhibitor ◽  
Grade 3

e15676 Background: The prognosis for patients (pts) with advanced hepatocellular carcinoma (HCC) after failure of sorafenib is poor, with few systemic therapy options. c-Met is a receptor tyrosine kinase implicated in the progression of HCC. Tepotinib, a highly selective c-Met inhibitor, has shown activity first-line in patients with c-Met+ HCC. We report final results of a phase Ib study of tepotinib in pts with advanced HCC after failure of first-line sorafenib. Methods: Eligible pts were ≥18 years with advanced HCC, Child-Pugh Class A, ECOG PS 0-1, and progression after ≥4 weeks of sorafenib. Tepotinib doses of 300 and 500 mg/day on a 21-day cycle were explored to establish the recommended phase II dose (RP2D) of tepotinib. Secondary objectives included antitumor activity by RECIST v1.1, biochemical response, and safety. Results: Seventeen pts were enrolled: 4 pts received tepotinib 300 mg/day and 13 pts 500 mg/day, confirmed as the RP2D. Fourteen pts experienced treatment-related adverse events (TRAEs), the most frequent being peripheral edema (n = 5, 2 grade 3), lipase increase (2, 1 grade 3), acute kidney injury (2, 1 grade 3), renal impairment (2, 1 grade 3), fatigue (2), nausea (2), asthenia (2). One pt with peripheral edema permanently discontinued treatment. No grade ≥4 TRAEs and no dose-limiting toxicities (DLTs) were reported. The best overall response was partial response (PR) in 2 pts and stable disease (SD) in 4 pts. The duration of the PRs was 57 and 91 weeks. In the first of these pts, tumor size decreased by 55% and serum alfa-fetoprotein (AFP) levels had decreased from 15,923 μg/L at baseline to < 3,000 μg/L by day 15 of cycle 2 and remained at this level until progression. In the second pt, tumor size decreased by > 60% from baseline. No consistent change in AFP was seen in pts with SD. Median overall survival was 7.2 months (range 0.7–22.9 months). Conclusions: The RP2D of tepotinib as second-line therapy for pts with advanced HCC who progress after sorafenib treatment is 500 mg/day. Tepotinib was well tolerated at this dose and showed signs of activity. The ongoing phase II part of this trial is investigating the efficacy and safety of tepotinib 500 mg/day in pts with c-Met+ HCC. Clinical trial information: NCT02115373.

Phase II Study of Gemcitabine and Oxaliplatin in Combination With Bevacizumab in Patients With Advanced Hepatocellular Carcinoma

2006 ◽  
Vol 24 (12) ◽  
pp. 1898-1903 ◽  
Author(s):  
Andrew X. Zhu ◽  
Lawrence S. Blaszkowsky ◽  
David P. Ryan ◽  
Jeffrey W. Clark ◽  
Alona Muzikansky ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Progression Free Survival ◽  
Vascular Tumor ◽  
Advanced Hepatocellular Carcinoma ◽  
Close Monitoring ◽  
Grade 3 ◽  
Transient Elevation

Purpose Hepatocellular carcinoma (HCC) is a vascular tumor with poor prognosis. Given the reported activity of gemcitabine and oxaliplatin (GEMOX) in HCC and the potential benefits of targeting the vascular endothelial growth factor pathway with bevacizumab (B), a phase II study of GEMOX-B was undertaken to define efficacy and toxicity profiles in HCC patients. Patients and Methods Eligible patients had pathologically proven measurable unresectable or metastatic HCC. For cycle 1 (14 days), bevacizumab 10 mg/kg was administered alone intravenously on day 1. For cycle 2 and beyond (28 days/cycle), bevacizumab 10 mg/kg was administered on days 1 and 15, gemcitabine 1,000 mg/m2 was administered as a dose rate infusion at 10 mg/m2/min followed by oxaliplatin at 85 mg/m2 on days 2 and 16. Results Thirty-three patients were enrolled and 30 patients were assessable for efficacy. The objective response rate was 20%, and 27% of patients had stable disease. Median overall survival was 9.6 months (95% CI, 8.0 months to not available) and median progression-free survival (PFS) was 5.3 months (95% CI, 3.7 to 8.7 months); the PFS rate at 3 and 6 months was 70% (95% CI, 54% to 85%) and 48% (95% CI, 31% to 65%), respectively. The most common treatment-related grade 3 to 4 toxicities included leukopenia/neutropenia, transient elevation of aminotransferases, hypertension, and fatigue. Conclusion GEMOX-B could be safely administered with close monitoring and had moderate antitumor activity for patients with advanced HCC. The high 6-month PFS rate is encouraging, and this regimen is worthy of further investigation.

A multicenter phase II study of sorafenib, capecitabine, and oxaliplatin (SECOX) in patients with advanced hepatocellular carcinoma: Final results of Hong Kong-Singapore Hepatocellular Carcinoma Research Collaborative Group study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4117-4117 ◽  
Author(s):  
Thomas Cheung Yau ◽  
Foon Yiu Cheung ◽  
Francis Lee ◽  
Su Pin Choo ◽  
Hilda Wong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Asian Population ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Collaborative Group ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Grade One

4117 Background: This is a single arm, multi-center, phase II study to assess the efficacy and tolerability of sorafenib, oxaliplatin and capecitabine combination for the treatment of advanced hepatocellular carcinoma (HCC) patients. Methods: Eligible patients received SECOX regime—sorafenib 400 mg bid (Day one-fourteen), oxaliplatin 85 mg/m2 (Day one) and capecitabine 1700 mg/m2(Day one-seven) every two weeks. Response assessment was based on RECIST 1.0 criteria. The primary endpoint was time-to-progression (TTP) and the secondary endpoints were tumor response rate (RR), progression-free survival (PFS), overall survival (OS) and tolerability. Results: A total of 51 patients were enrolled in the trial.The median age was 58 years (range, 28-81) and 84% of patients were chronic hepatitis B carriers. Ninety percent of recruited patients belonged to BCLC stage C disease and 41 (80%) patients had extra-hepatic metastasis. The best RR was 16% and they were all partial response. Another 62% of patients achieved stable disease for at least eight weeks. The median TTP was 5.29 months (95% CI 3.81-5.88 months), PFS 5.26 months (95% CI 3.75-5.88 months) and OS was 11.73 months (95% CI 8.87- 15.38 months). Diarrhea (75%), Hand-foot-skin reaction (73%) and transient liver function derangement were the most commonly encountered adverse events, with the majority of patients having grade one or two. No treatment-related death was reported. Conclusions: The SECOX regime indicates preliminary promising activity and safety in Asian population with advanced HCC. Our data support a randomized trial comparing SECOX versus sorafenib alone for treatment of advanced HCC. Clinical trial information: NCT00752063.

Combination of capecitabine, oxaliplatin with bevacizumab in treatment of advanced hepatocellular carcinoma (HCC): A phase II study

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 4574-4574 ◽  
Author(s):  
W. Sun ◽  
D. G. Haller ◽  
K. Mykulowycz ◽  
M. Rosen ◽  
M. Soulen ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Female Ratio ◽  
Advanced Hcc ◽  
Standard Chemotherapy Regimen ◽  
Hand Foot Syndrome ◽  
Number Of Treatment

4574 Background: Hepatocellular carcinoma (HCC) is one of the most common cancers globally and its incidence of in USA is increasing. Unfortunately, most patients with HCC are unsuitable for surgical resection or transplantation. Because of the heterogeneity of this disease and poor liver function in many patients, there is no generally accepted standard chemotherapy regimen for HCC. Efforts have been made to investigate effective and tolerable therapy for patients with advanced HCC. We conducted a phase II study to evaluate the efficacy and feasibility of the combination of bevacizumab, oxaliplatin and capecitabine in patients with advanced or metastatic HCC. The primary goal of the study was to evaluate the progression-free survival rate. The secondary endpoints include response, overall survival and toxicity. Methods: Patients with advanced or unresectable untransplantable metastatic HCC who had adequate bone marrow, liver and renal function (ANC ≥ 1,500/mm3, platelets ≥ 75,000/mm3, serum creatinine ≤ 2.0 mg/dl, total bilirubin ≤ 3.0 mg/dl, transaminases ≤ 5 upper limit of normal, and INR ≤ 1.5) were eligible to the study. Bevacizumab (5 mg/kg) and oxaliplatin (130 mg/m2) were administered intravenously day 1 of each 21- day cycle. Capecitabine (825 mg/m2, twice a day) was administered days 1 to 14. Results: Thirty patients (male/female ratio of 23/7) have been enrolled, with a median age of 57 (range 23–85). The average number of treatment cycles was 8 (2–25 cycles). Of evaluable patients, 3 patients (11%) achieved partial response, 21 patients had stable disease (78%) with a disease control rate of 89%. The mean PFS was 5.4 months with 3- and 6- months PFS of 70%, and 40%. There were 33% Gr. 2/3 oxaliplatin-related peripheral neuropathy and 11 % capecitabine-related Gr. 2/3 hand- foot syndrome. One patient had gastrointestinal perforation and sepsis after his first administration of bevacizumab and oxaliplatin. Two patients had esophageal varices-related bleeding, likely disease-related. Conclusions: The results demonstrate that the combination of bevacizumab, oxaliplatin and capecitabine is effective and tolerable in treatment of advanced HCC and should be considered for the further investigation. [Table: see text]

scholarly journals Efficacy, Safety, and Potential Biomarkers of Sunitinib Monotherapy in Advanced Hepatocellular Carcinoma: A Phase II Study

2009 ◽  
Vol 27 (18) ◽  
pp. 3027-3035 ◽  
Author(s):  
Andrew X. Zhu ◽  
Dushyant V. Sahani ◽  
Dan G. Duda ◽  
Emmanuelle di Tomaso ◽  
Marek Ancukiewicz ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Phase Ii ◽  
Kinase Inhibitor ◽  
Phase Ii Study ◽  
Objective Response ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Advanced Hepatocellular Carcinoma ◽  
Advanced Hcc ◽  
Sunitinib Treatment

PurposeTo assess the safety and efficacy of sunitinib in patients with advanced hepatocellular carcinoma (HCC) and explore biomarkers for sunitinib response.Patients and MethodsWe conducted a multidisciplinary phase II study of sunitinib, an antivascular endothelial growth factor receptor tyrosine kinase inhibitor, in advanced HCC. Patients received sunitinib 37.5 mg/d for 4 weeks followed by 2 weeks of rest per cycle. The primary end point was progression-free survival (PFS). We used functional magnetic resonance imaging to evaluate vascular changes in HCC after sunitinib treatment. Circulating molecular and cellular biomarkers were evaluated before and at six time points after sunitinib treatment.ResultsThirty-four patients were enrolled. The objective response rate was 2.9%, and 50% of patients had stable disease. Median PFS was 3.9 months (95% CI, 2.6 to 6.9 months), and overall survival was 9.8 months (95% CI, 7.4 months to not available). Grade 3 or 4 toxicities included leukopenia/neutropenia, thrombocytopenia, elevation of aminotransferases, and fatigue. Sunitinib rapidly decreased vessel leakiness, and this effect was more pronounced in patients with delayed progression. When evaluated early (at baseline and day 14) as well as over three cycles of treatment, higher levels of inflammatory molecules (eg, interleukin-6, stromal-derived factor 1α, soluble c-KIT) and circulating progenitor cells were associated with a poor outcome.ConclusionSunitinib shows evidence of modest antitumor activity in advanced HCC with manageable adverse effects. Rapid changes in tumor vascular permeability and circulating inflammatory biomarkers are potential determinants of response and resistance to sunitinib in HCC. Our study suggests that control of inflammation might be critical for improving treatment outcome in advanced HCC.

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