Phase II Trial of Sorafenib Combined With Concurrent Transarterial Chemoembolization With Drug-Eluting Beads for Hepatocellular Carcinoma

Purpose To evaluate safety and efficacy of combined transarterial chemoembolization (TACE) with doxorubicin-eluting beads (DEB) and sorafenib in patients with advanced hepatocellular carcinoma (HCC). Patients and Methods A prospective single-center phase II study was undertaken involving patients with unresectable HCC. The protocol involved sorafenib 400 mg twice per day combined with DEB-TACE. Safety and response were assessed. Results DEB-TACE in combination with sorafenib was successfully administered in 35 patients: mean age, 63 years; Child's A, 89%; Barcelona Clinic Liver Cancer stage C, 64%; Eastern Cooperative Oncology Group performance status of 0 and 1, 46% and 54%, respectively; and mean index tumor size, 7.7 cm (standard deviation, ± 4.2 cm). Patients underwent 128 cycles of therapy (sorafenib plus DEB-TACE, 60 cycles; sorafenib alone, 68 cycles). Median number of cycles per patient was two (range, one to five cycles); median number of days treated with sorafenib was 71 (range, 4 to 620 days). The most common toxicities during cycle one were fatigue (94%), anorexia (67%), alterations in liver enzymes (64%), and dermatologic adverse effects (48%). Although most patients experienced at least one grade 3 to 4 toxicity, most toxicities were minor (grade 1 to 2, 83% v grade 3 to 4, 17%). Toxicity during cycle two was decreased. Over the course of the study, there were 40 sorafenib dose interruptions and 25 sorafenib dose reductions. Sorafenib plus DEB-TACE was associated with a disease control rate of 95% (Response Evaluation Criteria in Solid Tumors Group)/100% (European Association for the Study of the Liver [EASL]), with an objective response of 58% (EASL). Conclusion The combination of sorafenib and DEB-TACE in patients with unresectable HCC is well tolerated and safe, with most toxicities related to sorafenib. Toxicity is manageable with dose adjustment of sorafenib. Preliminary efficacy data are promising.

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Avelumab in Combination with Axitinib as First-Line Treatment in Patients with Advanced Hepatocellular Carcinoma: Results from the Phase 1b VEGF Liver 100 Trial

Liver Cancer ◽

10.1159/000514420 ◽

2021 ◽

pp. 1-11

Author(s):

Masatoshi Kudo ◽

Kenta Motomura ◽

Yoshiyuki Wada ◽

Yoshitaka Inaba ◽

Yasunari Sakamoto ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Kinase Inhibitor ◽

Group Performance ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Clinical Activity ◽

Advanced Hepatocellular Carcinoma ◽

Recist 1.1 ◽

Phase 1B ◽

Grade 3

Introduction: Combining an immune checkpoint inhibitor with a targeted antiangiogenic agent may leverage complementary mechanisms of action for the treatment of advanced/metastatic hepatocellular carcinoma (aHCC). Avelumab is a human anti-PD-L1 IgG1 antibody with clinical activity in various tumor types; axitinib is a selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors 1, 2, and 3. We report the final analysis from VEGF Liver 100 (NCT03289533), a phase 1b study evaluating safety and efficacy of avelumab plus axitinib in treatment-naive patients with aHCC. Methods: Eligible patients had confirmed aHCC, no prior systemic therapy, ≥1 measurable lesion, Eastern Cooperative Oncology Group performance status ≤1, and Child-Pugh class A disease. Patients received avelumab 10 mg/kg intravenously every 2 weeks plus axitinib 5 mg orally twice daily until progression, unacceptable toxicity, or withdrawal. Endpoints included safety and investigator-assessed objective response per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and modified RECIST (mRECIST) for HCC. Results: Twenty-two Japanese patients were enrolled and treated with avelumab plus axitinib. The minimum follow-up was 18 months as of October 25, 2019 (data cutoff). Grade 3 treatment-related adverse events (TRAEs) occurred in 16 patients (72.7%); the most common (≥3 patients) were hypertension (n = 11 [50.0%]), palmar-plantar erythrodysesthesia syndrome (n = 5 [22.7%]), and decreased appetite (n = 3 [13.6%]). No grade 4 TRAEs or treatment-related deaths occurred. Ten patients (45.5%) had an immune-related AE (irAE) of any grade; 3 patients (13.6%) had an infusion-related reaction (IRR) of any grade, and no grade ≥3 irAE and IRR were observed. The objective response rate was 13.6% (95% CI: 2.9–34.9%) per RECIST 1.1 and 31.8% (95% CI: 13.9–54.9%) per mRECIST for HCC. Conclusion: Treatment with avelumab plus axitinib was associated with a manageable toxicity profile and showed antitumor activity in patients with aHCC.

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Phase II Trial of the Combination of Bevacizumab and Erlotinib in Patients Who Have Advanced Hepatocellular Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2008.18.3301 ◽

2009 ◽

Vol 27 (6) ◽

pp. 843-850 ◽

Cited By ~ 231

Author(s):

Melanie B. Thomas ◽

Jeffrey S. Morris ◽

Romil Chadha ◽

Michiko Iwasaki ◽

Harmeet Kaur ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Response Rate ◽

Group Performance ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Evaluation Criteria ◽

Progression Free Survival ◽

Advanced Hepatocellular Carcinoma ◽

Study Objective ◽

Advanced Hcc

Purpose The study objective was to determine the proportion of patients with hepatocellular carcinoma (HCC) treated with the combination of bevacizumab (B) and erlotinib (E) who were alive and progression free at 16 weeks (16-week progression-free survival [PFS16]) of continuous therapy. Secondary objectives included response rate, median PFS, survival, and toxicity. Patients and Methods Patients who had advanced HCC that was not amenable to surgical or regional therapies, up to one prior systemic treatment; Childs-Pugh score A or B liver function; Eastern Cooperative Oncology Group performance status 0, 1, or 2 received B 10 mg/kg every 14 days and E 150 mg orally daily, continuously, for 28-day cycles. Tumor response was evaluated every 2 cycles by using Response Evaluation Criteria in Solid Tumors Group criteria. A total of 40 patients were treated. Results The primary end point of PFS16 was 62.5%. Ten patients achieved a partial response for a confirmed overall response rate (intent-to-treat) of 25%. The median PFSevent was 39 weeks (95% CI, 26 to 45 weeks; 9.0 months), and the median overall survival was 68 weeks (95% CI, 48 to 78 weeks; 15.65 months). Grades 3 to 4 drug-related toxicity included fatigue (n = 8; 20%), hypertension (n = 6; 15%), diarrhea (n = 4; 10%) elevated transaminases (n = 4; 10%), gastrointestinal hemorrhage (n = 5; 12.5%), wound infection (n = 2; 5%) thrombocytopenia (n = 1; 2.5%), and proteinuria, hyperbilirubinemia, back pain, hyperkalemia, and anorexia (n = 1 each). Conclusion The combination of B + E in patients who had advanced HCC showed significant, clinically meaningful antitumor activity. B + E warrant additional evaluation in randomized controlled trials.

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Impact of Individual Components of the Metabolic Syndrome on the Outcome of Patients with Advanced Hepatocellular Carcinoma Treated with Sorafenib

Digestive Diseases ◽

10.1159/000477578 ◽

2017 ◽

Vol 36 (1) ◽

pp. 78-88 ◽

Cited By ~ 4

Author(s):

Christian Labenz ◽

Vera Prenosil ◽

Sandra Koch ◽

Yvonne Huber ◽

Jens U. Marquardt ◽

...

Keyword(s):

Diabetes Mellitus ◽

Hepatocellular Carcinoma ◽

Metabolic Syndrome ◽

Group Performance ◽

Performance Status ◽

Eastern Cooperative Oncology Group ◽

Advanced Hepatocellular Carcinoma ◽

Advanced Hcc ◽

The Metabolic Syndrome ◽

The Impact

Background/Aim: Individual components of the metabolic syndrome (MS) such as obesity or diabetes mellitus impair the prognosis of patients with hepatocellular carcinoma (HCC) following curative treatment approaches or transarterial therapies. The aim of this retrospective study was to assess the impact of these factors on the overall survival (OS) of patients with advanced HCC treated with sorafenib. Methods: Univariate and multivariate analyses were performed to assess the impact of individual components of the MS on the OS of 152 consecutive patients with advanced HCC treated with sorafenib. Results: The presence of overweight/obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and of the MS itself did not impair the median OS. Multivariate analysis showed that Eastern Cooperative Oncology Group Performance Status ≥1 (hazards ratio [HR] 2.03), presence of macrovascular invasion (HR 1.71), Child-Pugh score B/C (HR 2.19), tumor grading G3 (HR 2.17), no prior HCC treatment (HR 2.34), and the presence of 2 or more out of 5 individual components of the MS (HR 0.65) were independent prognostic factors regarding the median OS. Conclusions: Our investigations do not confirm a negative prognostic role of individual components of the MS or the MS itself for patients with advanced HCC treated with sorafenib.

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A real-world study of camrelizumab in the treatment of hepatocellular carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16121 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16121-e16121

Author(s):

Yong-Yi Zeng ◽

Wu-hua Guo ◽

Zhibo Zhang ◽

Xi Shi ◽

Yongjie Su ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Real World ◽

Group Performance ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Chinese Patients ◽

Advanced Hepatocellular Carcinoma ◽

Phase Ii Studies ◽

Clinical Trial Information

e16121 Background: Programmed cell death protein‐1(PD-1) targeted immunotherapy is a promising treatment strategy for advanced hepatocellular carcinoma. Anti-PD-1 inhibitor camrelizumab showed antitumour activity in phase II studies of advanced hepatocellular carcinoma, with manageable toxicities. This study evaluates safety and efficacy of camrelizumab in patients with advanced hepatocellular carcinoma. Methods: This is a multicentre, real‐world trial done at thirty-three centres in Fujian Province, China. Eligible patients were aged 18 to 75 years was diagnosed by China Liver Cancer Staging(CNLC) 2019 clinical diagnostic criteria or with a histological or cytological diagnosis of advanced hepatocellular carcinoma, unresectable or had progressed on or were intolerant to previous systemic treatment, and had an Eastern Cooperative Oncology Group performance score of 0-1. Patients were received camrelizumab 200 mg intravenously every 2 weeks plus other treatments, such as molecular targeted drug, transcatheyer artetial chemoembolization, radiotherapy and chemotherapy. The primary endpoints were progression-free survival. Safety was analysed in all treated patients. Follow-up is ongoing. Results: Between Mar 12, 2020, and Dec 25, 2020, 63 patients were screened for eligibility, of whom 41 eligible patients received camrelizumab were recruited and among whom 15 received apatinib, 16 received lenvatinib, 2 received sorafenib and 1 received regorafenib. Median followup was 5.28 months (IQR 1.63–10.20). Objective response was reported in 12 (29.3%; 95% CI 16.1–45.5) of 41 patients. Disease control was reported in 34 (82.9%; 95% CI 67.9–92.8) of 41 patients. The median PFS was not reached, and expected more than 9 months. Grade 3 or 4 treatment-related adverse events occurred in 21 (51.2%) of 41 patients; the most common were increased gamma-glutamyltransferase (15 [36.6%]) and increased aspartate aminotransferase (7 [17%]). One death was judged by the investigators to be potentially treatment-related (due to upper gastrointestinal bleeding). Conclusions: Camrelizumab showed promising efficacy and safety in pretreated Chinese patients with advanced hepatocellular carcinoma, and might represent a new treatment option for these patients. Clinical trial information: ChiCTR2000041405. Research Sponsor: Jiangsu Hengrui Medicine Co., Ltd. Clinical trial information: ChiCTR2000041405.

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Radioembolization in Advanced Hepatocellular Carcinoma

Journal of Clinical Oncology ◽

10.1200/jco.2018.77.7227 ◽

2018 ◽

Vol 36 (19) ◽

pp. 1898-1901 ◽

Cited By ~ 3

Author(s):

Ahsun Riaz ◽

Robert Lewandowski ◽

Riad Salem

Keyword(s):

Hepatocellular Carcinoma ◽

Portal Vein ◽

Group Performance ◽

Performance Status ◽

Relevant Literature ◽

Eastern Cooperative Oncology Group ◽

Distant Metastases ◽

Advanced Hepatocellular Carcinoma ◽

Vein Thrombosis ◽

Management Approaches

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors’ suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. A 68-year-old man with a remote history of alcohol abuse presented with vague abdominal pain. A review of systems suggested the patient had an Eastern Cooperative Oncology Group performance status 1 (restriction of strenuous physical activity). There were no physical examination findings of note. Laboratory studies disclosed Child-Pugh A liver status (no ascites; no encephalopathy; total bilirubin, 1 mg/dL; albumin, 3.5 g/dL; and international normalized rato, 1.2). The alpha-fetoprotein was mildly elevated (19.5 ng/mL). Magnetic resonance imaging with contrast disclosed an infiltrative mass with extensive malignant right and left portal vein thrombosis ( Fig 1A ) with cavernous transformation of the portal vein. The infiltrative mass ( Fig 2A ) was biopsied, revealing hepatocellular carcinoma. No distant metastases were found on a bone scintigraphy or computerized tomography scan. Given these features, this patient was classified as Barcelona Clinic for Liver Cancer stage C. The patient was referred for management of advanced hepatocellular carcinoma.

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EAGLE: A phase 3, randomized, open-label study of durvalumab (D) with or without tremelimumab (T) in patients (pts) with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC).

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.6012 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 6012-6012 ◽

Cited By ~ 20

Author(s):

Lisa F. Licitra ◽

Robert I. Haddad ◽

Caroline Even ◽

Makoto Tahara ◽

Mikhail Dvorkin ◽

...

Keyword(s):

Group Performance ◽

Checkpoint Inhibitors ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Standard Of Care ◽

Open Label ◽

Phase 3 ◽

Risk Of Death ◽

Grade 3

6012 Background: EAGLE is a phase 3 study evaluating efficacy of D (anti-PD-L1 mAb) monotherapy and D+T (anti-CTLA-4 mAb) vs standard of care (SOC) in pts with R/M HNSCC who progressed following platinum-based therapy (NCT02369874). Methods: Pts were randomized 1:1:1 to D 10 mg/kg IV every 2 weeks (Q2W), D+T (D 20 mg/kg IV Q4W + T 1 mg/kg IV Q4W for 4 doses, then D 10 mg/kg IV Q2W), or SOC (investigator’s choice: cetuximab, taxane, methotrexate, or fluoropyrimidine-based regimen). The primary endpoint was overall survival (OS) with dual primary objectives of D+T vs SOC and D vs SOC. Additional endpoints included objective response rate (ORR), duration of response (DoR), and adverse events (AEs). Results: 240 pts were randomized to D, 247 to D+T and 249 to SOC. An imbalance for Eastern Cooperative Oncology Group performance status (ECOG PS) was seen in favor of the SOC arm (D, PS 0 = 26%, PS 1 = 74%; D+T, PS 0 = 26%, PS 1 = 74%; SOC, PS 0 = 32%, PS 1 = 68%). The risk of death was not statistically significantly different for D compared with SOC (HR: 0.88; 95% CI: 0.72–1.08; P = 0.20) or D+T vs SOC (HR: 1.04; 95% CI: 0.85–1.26; P = 0.76). Efficacy data are provided in the table. Treatment-related AEs Grade ≥3 were reported in 10.1% of pts (regardless of causality Grade ≥3 AEs were 41.4%) in the D arm, 16.3% (51.2%) for D+T, and 24.2% (44.2%) for SOC. Following treatment, 2% of pts in D, 5% in D+T and 15% in SOC received immunotherapy. Conclusions: D and D+T did not demonstrate a statistically significant improvement in OS compared to standard chemotherapy in pts with R/M HNSCC. Median OS and ORR of D arm were similar to other studies with checkpoint inhibitors. The SOC arm outperformed what has been seen for SOC arms in previous studies; subsequent immunotherapy may have confounded the OS analyses. The safety profile for D and D + T in R/M HNSCC is consistent with previous trials. Clinical trial information: NCT02369874. [Table: see text]

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A phase II study of the halichondrin B analog, E7389, in patients (pts) with advanced non-small cell lung cancer (NSCLC) previously treated with a taxane. A California Consortium/University of Pittsburgh/University of Chicago NCI/CTEP sponsored trial

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.8056 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 8056-8056

Author(s):

B. J. Gitlitz ◽

A. M. Davies ◽

C. P. Belani ◽

A. Argiris ◽

S. S. Ramalingam ◽

...

Keyword(s):

Phase Ii ◽

Performance Status ◽

Objective Response ◽

Previous Treatment ◽

Progression Free Survival ◽

Median Number ◽

Disease Rate ◽

Hematologic Toxicity ◽

Halichondrin B ◽

Grade 3

8056 Background: E7389 is a structurally simplified synthetic macrocyclic ketone analog of halichondrin B and has a unique mechanism of microtubule binding and interaction, distinct from other agents in this class. Thus, it was our hypothesis that pts with prior taxane based therapy would respond to this agent. We conducted a phase II trial of E7389 in prior taxane-treated NSCLC pts. Methods: Eligible pts included: histologically confirmed advanced NSCLC, previous treatment with platinum-based therapy and a taxane, no more than 2 prior regimens, measurable disease, Zubrod performance status ≤ 2. Pts were classified by taxane-sensitivity status: taxane sensitive (TS) (progression >90 days after taxane) or taxane resistant (TR) (progression during or ≤90 days after taxane). Treatment: E7389 1.4 mg/m2 intravenously over 1–2 minutes on day 1 and 8 of a 21 day schedule until disease progression or unacceptable toxicity. Results: 41 pts were entered. There were 3 (15%) objective responses (7.2+, 8.5+, 10.6 mo) of 20 TS pts; and no response of 21 TR pts. Stable disease rate was 60% and 24% in TS and TR pts. respectively. Median progression free survival (PFS) is 6.3 mos TS pts. 95%CI (2.5–8.6 mos) and 1.2 mos TR pts. 95%CI (1.1–4.1 mos). Median number of cycles (range): TS 4 (1–14); TR 2 (1–7). Major toxicity included: 19 pts (46%) with grade 3 or 4 hematologic toxicity including only 1 episode of febrile neutropenia and 8 pts (20%) with grade 3 or 4 non-hematologic toxicity attributable to drug including: fatigue (1), dehydration (2), nausea (2), constipation (2). Only 1 pt developed grade 3 neuropathy (course 9). Conclusions: E7389 was well tolerated with encouraging objective response, PFS and disease control rate in the TS cohort. This cohort will be expanded, using a 2-stage design, to accrue up to another 25 pts. No significant financial relationships to disclose.

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

Journal of Clinical Oncology ◽

10.1200/jco.2005.04.9130 ◽

2006 ◽

Vol 24 (12) ◽

pp. 1898-1903 ◽

Cited By ~ 275

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.

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A multicenter phase II study of sorafenib in Japanese patients with hepatocellular carcinoma and Child Pugh A or B cirrhosis.

Journal of Clinical Oncology ◽

10.1200/jco.2014.32.3_suppl.354 ◽

2014 ◽

Vol 32 (3_suppl) ◽

pp. 354-354

Author(s):

Eiichiro Suzuki ◽

Shuichi Kaneko ◽

Takuji Okusaka ◽

Masafumi Ikeda ◽

Kensei Yamaguchi ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Overall Survival ◽

Performance Status ◽

Objective Response ◽

Japanese Patients ◽

Advanced Hepatocellular Carcinoma ◽

Efficacy And Safety ◽

Class A ◽

Pugh Class ◽

Grade 3

354 Background: Sorafenib has been used as the first-line treatment for advanced hepatocellular carcinoma (HCC), however, its efficacy and safety in Japanese patients (pts), especially those with Child-Pugh (CP) B cirrhosis, have not yet been fully examined. This study was conducted to evaluate the efficacy and safety of sorafenib in Japanese pts with HCC and CP B or CP A cirrhosis. Methods: The eligibility criteria were patients 1) with pathologically or clinically proven HCC, 2) with an ECOG performance status 0 to 2, 3) aged 20 to 79 years, 4) with measurable lesions, 5) with adequate hematological, renal and Child Pugh class A or B liver functions. Sorafenib was administered orally at the dose of 400 mg twice daily. Administration was continued until the detection of disease progression or appearance of unacceptable toxicity. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints included objective response, overall survival (OS), and toxicity. Results: Forty CP A pts and 12 CP B pts were enrolled between April 2010 and January 2012. The median PFS in the CP A pts was 3.3 months (M) and that in the CP B pts was 3.2 M. Among the pts with CP A, there was one patient with confirmed complete response (2.5%), 3 pts with partial response (7.5%), and 19 pts (47.5%) with stable disease (SD). Among the pts with CP B, there were no treatment responses, and 8 (66.7%) pts had SD. The median overall survival in the CP A pts was 13.4 M and that in the CP B pts was 7.4 M. With regard to toxicities, fewer CP A pts experienced grade 3/4 toxicities than CP B pts (77.5% vs. 91.6%). The grade 3/4 toxicities in the CP A and B pts, respectively, included thrombocytopenia (10% and 25%), hand foot skin reaction (27.5% and 16.7%), Erythema multiforme (0% and 16.7%), and upper gastrointestinal bleeding (0% and 16.7%). There were no treatment-related deaths in either group of patients. Conclusions: This study shows that sorafenib is effective and well-tolerated in Japanese patients with HCC and Child Pugh class A liver cirrhosis, consistent with previous reports. The outcome was poorer and severe toxicities were more frequent in patients with Child Pugh B cirrhosis than in those with Child Pugh A cirrhosis. Clinical trial information: 000002972.

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Phase II Multicenter Trial of Bevacizumab Plus Fluorouracil and Leucovorin in Patients With Advanced Refractory Colorectal Cancer: An NCI Treatment Referral Center Trial TRC-0301

Journal of Clinical Oncology ◽

10.1200/jco.2005.05.1573 ◽

2006 ◽

Vol 24 (21) ◽

pp. 3354-3360 ◽

Cited By ~ 130

Author(s):

Helen X. Chen ◽

Margaret Mooney ◽

Matthew Boron ◽

Don Vena ◽

Kimberly Mosby ◽

...

Keyword(s):

Group Performance ◽

Bowel Perforation ◽

Performance Status ◽

Objective Response ◽

Eastern Cooperative Oncology Group ◽

Progression Free Survival ◽

Multicenter Trial ◽

Eligibility Criteria ◽

Referral Center ◽

Grade 3

Purpose To provide bevacizumab (BV) -based therapy to patients with advanced colorectal cancers (CRC) who had exhausted standard chemotherapy options, and to evaluate the response to BV combined with fluorouracil (FU) and leucovorin (LV) in this patient population. Patients and Methods This was a multicenter, single-arm treatment trial conducted under the National Cancer Institute Treatment Referral Center network nationwide. Patients were treated with BV 5 mg/kg every 2 weeks combined with FU/LV; FU was administered by bolus or continuous infusion. Eligibility criteria included advanced CRC that had progressed after irinotecan- and oxaliplatin-based chemotherapy, Eastern Cooperative Oncology Group performance status 0 to 2, and absence of thromboembolism. The primary end point was objective response rate (RR) in the first 100 assessable patients. All patients received follow-up for toxicity and survival. Results Due to rapid accrual, a total of 350 patients were enrolled at 32 participating sites nationwide by October 2003. In the initially planned cohort of 100 assessable patients, the objective RR was 4% (95% CI, 1.1% to 9.9%) by investigators' assessment and 1% (95% CI, 0% to 5.5%) based on independent review; median progression-free survival was 3.5 months and median overall survival was 9.0 months. The safety profile was similar to prior BV trials in CRC. Grade 3 to 4 hemorrhage occurred in 5% of patients, including 3.8% with bleeding in the GI tract. Other adverse events such as hypertension, thrombosis, and bowel perforation were also observed at rates consistent with other studies. Conclusion For patients with advanced CRC that had progressed after both irinotecan-based and oxaliplatin-based chemotherapy regimens, the combination of BV and FU/LV was associated with rare objective responses.

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