Phase II study of NGR-hTNF in combination with doxorubicin in relapsed ovarian cancer patients.
BACKGROUND
The NGR-hTNF (asparagine-glycine-arginine-human tumour necrosis factor) is able to promote antitumour immune responses and to improve the intratumoural doxorubicin uptake by selectively damaging tumour blood vessels.


METHODS
Patients progressing after ≥ 1 platinum/taxane-based regimen received NGR-hTNF 0.8 μg m(-2) and doxorubicin 60 mg m(-2) every 3 weeks. Primary endpoint was a Response Evaluation Criteria in Solid Tumors-defined response rate with a target of more than 6 out of 37 responding patients.


RESULTS
A total of 37 patients with platinum-free interval lower than 6 months (PFI<6; n=25), or between 6 and 12 months (PFI=6-12; n=12) were enrolled. Median baseline peripheral blood lymphocyte count (PBLC) was 1.6 per ml (interquartile range, 1.2-2.1). In all, 18 patients (49%) received more than 6 cycles. Febrile neutropaenia was registered in one patient (3%). Among 35 assessable patients, 8 (23%; 95% CI 12-39%) had partial response (2 with PFI<6; 6 with PFI=6-12) and 15 (43%) had stable disease (10 with PFI<6; 5 with PFI=6-12). Median progression-free survival (PFS) was 5.0 months for all patients, 3.8 months for patients with PFI<6, and 7.8 months for patients with PFI=6-12. Median overall survival (OS) was 17.0 months. Patients with baseline PBLC higher than the first quartile had improved PFS (P=0.01) and OS (P=0.001).


CONCLUSIONS
Tolerability and activity of this combination warrant further randomised testing in patients with PFI<6. The role of PBLC as a blood-based biomarker deserves further investigation.
Department of Gynecologic Oncology, Catholic University of Rome, Rome, Italy.
D
D
Lorusso
G
G
Scambia
G
G
Amadio
A
A
di Legge
A
A
Pietragalla
R
R
De Vincenzo
V
V
Masciullo
M
M
Di Stefano
G
G
Mangili
G
G
Citterio
M
M
Mantori
A
A
Lambiase
C
C
Bordignon
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000401:mortality; D017671:Platinum Compounds / Q000008:administration & dosage; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D043823:Taxoids / Q000008:administration & dosage; D017211:Treatment Failure; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage*
D001952:Bridged-Ring Compounds; D017671:Platinum Compounds; D011993:Recombinant Fusion Proteins; D043823:Taxoids; D014409:Tumor Necrosis Factor-alpha; C464839:tumor necrosis factor-alpha, CNGRC fusion protein, human; C080625:taxane; D004317:Doxorubicin