Limits...
Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma.

Gabrielson A, Tesfaye AA, Marshall JL, Pishvaian MJ, Smaglo B, Jha R, Dorsch-Vogel K, Wang H, He AR - Cancer Chemother. Pharmacol. (2015)

Bottom Line: The median PFS was 1.9 months, and median OS was 13.1 months.The combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC.However, the regimen failed to show survival benefit.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC, 20007, USA.

ABSTRACT

Purpose: To determine the antitumor efficacy and tolerability of combination temozolomide (TMZ) and veliparib (ABT-888) in patients with advanced, sorafenib-refractory hepatocellular carcinoma (HCC).

Methods: This single-arm phase II trial enrolled patients with pathologically confirmed, sorafenib-refractory HCC. All patients received 40 mg ABT-888 PO daily on days 1-7 and 150 mg/m(2) TMZ PO daily on days 1-5 of a 28-day cycle. The primary endpoint was objective response rate (ORR) at 2 months. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity profile. Tumor response was assessed every 2 cycles using RECIST criteria, and toxicities were assessed using CTCAE v4.03.

Results: We enrolled 16 patients in the first phase of the trial, but the study was discontinued due to a poor ORR; only four patients (25 %) had SD after 2 cycles. Twelve patients (75 %) were taken off study after 2 months of treatment; 10 of these had disease progression. Two patients (13 %) were taken off study due to severe toxicity, and one patient (6 %) died from non-treatment-related liver failure. One patient had SD for 16 months, receiving 11 cycles of therapy before being taken off study. The most common grade 3 treatment-related toxicities included vomiting (n = 2), thrombocytopenia (n = 2), nausea (n = 1), and anemia (n = 1). The median PFS was 1.9 months, and median OS was 13.1 months.

Conclusion: The combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC. However, the regimen failed to show survival benefit. CLINICALTRIALS.

Gov identifier: NCT01205828.

No MeSH data available.


Related in: MedlinePlus

Kaplan–Meier curve for progression-free survival
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4612326&req=5

Fig1: Kaplan–Meier curve for progression-free survival

Mentions: Median PFS (Fig. 1) and OS (Fig. 2) for the entire cohort were 1.9 months (95 % CI 1.8–2.0) and 13.1 months (95 % CI 0–32.0), respectively. Patients were stratified by serum AFP level, presence of tumor vascular invasion, Child-Pugh grade, and cellular differentiation to measure their association with OS and PFS. Using the log-rank test, we found that serum AFP, tumor vascular invasion, Child-Pugh grade, and cellular differentiation were not significantly associated with either OS or PFS after receiving the combination therapy (Supplementary Figures 1–8).Fig. 1


Phase II study of temozolomide and veliparib combination therapy for sorafenib-refractory advanced hepatocellular carcinoma.

Gabrielson A, Tesfaye AA, Marshall JL, Pishvaian MJ, Smaglo B, Jha R, Dorsch-Vogel K, Wang H, He AR - Cancer Chemother. Pharmacol. (2015)

Kaplan–Meier curve for progression-free survival
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4612326&req=5

Fig1: Kaplan–Meier curve for progression-free survival
Mentions: Median PFS (Fig. 1) and OS (Fig. 2) for the entire cohort were 1.9 months (95 % CI 1.8–2.0) and 13.1 months (95 % CI 0–32.0), respectively. Patients were stratified by serum AFP level, presence of tumor vascular invasion, Child-Pugh grade, and cellular differentiation to measure their association with OS and PFS. Using the log-rank test, we found that serum AFP, tumor vascular invasion, Child-Pugh grade, and cellular differentiation were not significantly associated with either OS or PFS after receiving the combination therapy (Supplementary Figures 1–8).Fig. 1

Bottom Line: The median PFS was 1.9 months, and median OS was 13.1 months.The combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC.However, the regimen failed to show survival benefit.

View Article: PubMed Central - PubMed

Affiliation: Division of Hematology and Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Hospital, 3800 Reservoir Road, NW, Washington, DC, 20007, USA.

ABSTRACT

Purpose: To determine the antitumor efficacy and tolerability of combination temozolomide (TMZ) and veliparib (ABT-888) in patients with advanced, sorafenib-refractory hepatocellular carcinoma (HCC).

Methods: This single-arm phase II trial enrolled patients with pathologically confirmed, sorafenib-refractory HCC. All patients received 40 mg ABT-888 PO daily on days 1-7 and 150 mg/m(2) TMZ PO daily on days 1-5 of a 28-day cycle. The primary endpoint was objective response rate (ORR) at 2 months. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity profile. Tumor response was assessed every 2 cycles using RECIST criteria, and toxicities were assessed using CTCAE v4.03.

Results: We enrolled 16 patients in the first phase of the trial, but the study was discontinued due to a poor ORR; only four patients (25 %) had SD after 2 cycles. Twelve patients (75 %) were taken off study after 2 months of treatment; 10 of these had disease progression. Two patients (13 %) were taken off study due to severe toxicity, and one patient (6 %) died from non-treatment-related liver failure. One patient had SD for 16 months, receiving 11 cycles of therapy before being taken off study. The most common grade 3 treatment-related toxicities included vomiting (n = 2), thrombocytopenia (n = 2), nausea (n = 1), and anemia (n = 1). The median PFS was 1.9 months, and median OS was 13.1 months.

Conclusion: The combination of TMZ and ABT-888 is well tolerated in patients with advanced HCC. However, the regimen failed to show survival benefit. CLINICALTRIALS.

Gov identifier: NCT01205828.

No MeSH data available.


Related in: MedlinePlus