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Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma.

Santoro A, Pressiani T, Citterio G, Rossoni G, Donadoni G, Pozzi F, Rimassa L, Personeni N, Bozzarelli S, Rossoni G, Colombi S, De Braud FG, Caligaris-Cappio F, Lambiase A, Bordignon C - Br. J. Cancer (2010)

Bottom Line: In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months.NGR-hTNF was well tolerated and showed single-agent activity in HCC.Further investigation in HCC is of interest.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Istituto Clinico Humanitas, Rozzano, Italy.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is a highly vascularised and poor-prognosis tumour. NGR-hTNF is a vascular-targeting agent consisting of human tumour necrosis factor-alpha fused to the tumour-homing peptide NGR, which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels.

Methods: Twenty-seven patients with advanced-stage disease resistant to either locoregional (59%; range, 1-3), systemic treatments (52%; range, 1-3) or both (33%) received NGR-hTNF 0.8 microg m(-2) once every 3 weeks. The primary aim of the study was progression-free survival (PFS).

Results: No grade 3-4 treatment-related toxicities were noted. Common toxicity included mild-to-moderate, short-lived chills (63%). Median PFS was 2.3 months (95% CI: 1.7-2.9). A complete response ongoing after 20 months was observed in a sorafenib-refractory patient and a partial response in a Child-Pugh class-B patient, yielding a response rate of 7%. Six patients (22%) experienced stable disease. The disease control rate (DCR) was 30% and was maintained for a median PFS time of 4.3 months. Median survival was 8.9 months (95% CI: 7.5-10.2). In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months.

Conclusion: NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest.

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Related in: MedlinePlus

Kaplan–Meier curves of progression-free (red line) and overall survival (blue line) in the cohort of 12 sorafenib-resistant patients, enrolled in the triweekly schedule (n=5) or weekly schedule (n=7). Vertical ticks denote censored observations.
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fig5: Kaplan–Meier curves of progression-free (red line) and overall survival (blue line) in the cohort of 12 sorafenib-resistant patients, enrolled in the triweekly schedule (n=5) or weekly schedule (n=7). Vertical ticks denote censored observations.

Mentions: Overall, the subset of 12 sorafenib-pretreated patients reported a response rate of 8% and a DCR of 33%, whereas the median PFS and survival were 2.1 and 9.5 months, respectively (Figure 5). All patients discontinued study treatment because of radiologically documented progressive disease. Median survival was 13 months, if recorded from the date of sorafenib therapy initiation. The median ratio between the PFS durations on the previous sorafenib therapy (median, 2.3 months; 95% CI: 2.1–2.4) and on the current study therapy (median, 2.1 months; 95% CI: 1.8–2.4) was 0.72, with four patients (33%) experiencing PFS durations equal or longer than those experienced while on the previous sorafenib therapy.


Activity and safety of NGR-hTNF, a selective vascular-targeting agent, in previously treated patients with advanced hepatocellular carcinoma.

Santoro A, Pressiani T, Citterio G, Rossoni G, Donadoni G, Pozzi F, Rimassa L, Personeni N, Bozzarelli S, Rossoni G, Colombi S, De Braud FG, Caligaris-Cappio F, Lambiase A, Bordignon C - Br. J. Cancer (2010)

Kaplan–Meier curves of progression-free (red line) and overall survival (blue line) in the cohort of 12 sorafenib-resistant patients, enrolled in the triweekly schedule (n=5) or weekly schedule (n=7). Vertical ticks denote censored observations.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2966632&req=5

fig5: Kaplan–Meier curves of progression-free (red line) and overall survival (blue line) in the cohort of 12 sorafenib-resistant patients, enrolled in the triweekly schedule (n=5) or weekly schedule (n=7). Vertical ticks denote censored observations.
Mentions: Overall, the subset of 12 sorafenib-pretreated patients reported a response rate of 8% and a DCR of 33%, whereas the median PFS and survival were 2.1 and 9.5 months, respectively (Figure 5). All patients discontinued study treatment because of radiologically documented progressive disease. Median survival was 13 months, if recorded from the date of sorafenib therapy initiation. The median ratio between the PFS durations on the previous sorafenib therapy (median, 2.3 months; 95% CI: 2.1–2.4) and on the current study therapy (median, 2.1 months; 95% CI: 1.8–2.4) was 0.72, with four patients (33%) experiencing PFS durations equal or longer than those experienced while on the previous sorafenib therapy.

Bottom Line: In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months.NGR-hTNF was well tolerated and showed single-agent activity in HCC.Further investigation in HCC is of interest.

View Article: PubMed Central - PubMed

Affiliation: Department of Oncology, Istituto Clinico Humanitas, Rozzano, Italy.

ABSTRACT

Background: Hepatocellular carcinoma (HCC) is a highly vascularised and poor-prognosis tumour. NGR-hTNF is a vascular-targeting agent consisting of human tumour necrosis factor-alpha fused to the tumour-homing peptide NGR, which is able to selectively bind an aminopeptidase N overexpressed on tumour blood vessels.

Methods: Twenty-seven patients with advanced-stage disease resistant to either locoregional (59%; range, 1-3), systemic treatments (52%; range, 1-3) or both (33%) received NGR-hTNF 0.8 microg m(-2) once every 3 weeks. The primary aim of the study was progression-free survival (PFS).

Results: No grade 3-4 treatment-related toxicities were noted. Common toxicity included mild-to-moderate, short-lived chills (63%). Median PFS was 2.3 months (95% CI: 1.7-2.9). A complete response ongoing after 20 months was observed in a sorafenib-refractory patient and a partial response in a Child-Pugh class-B patient, yielding a response rate of 7%. Six patients (22%) experienced stable disease. The disease control rate (DCR) was 30% and was maintained for a median PFS time of 4.3 months. Median survival was 8.9 months (95% CI: 7.5-10.2). In a subset of 12 sorafenib-resistant patients, the response rate was 8% and the median survival was 9.5 months.

Conclusion: NGR-hTNF was well tolerated and showed single-agent activity in HCC. Further investigation in HCC is of interest.

Show MeSH
Related in: MedlinePlus