Two doses of NGR-hTNF in combination with capecitabine plus oxaliplatin in colorectal cancer patients failing standard therapies.
BACKGROUND
asparagine-glycine-arginine-human tumour necrosis factor (NGR-hTNF), an agent selectively damaging the tumour vasculature, showed a biphasic dose-response curve in preclinical models. Previous phase I trials of NGR-hTNF indicated 0.8 and 45 μg/m(2) as optimal biological and maximum-tolerated dose, respectively.


METHODS
Two sequential cohorts of 12 colorectal cancer (CRC) patients who had failed standard therapies received NGR-hTNF 0.8 or 45 μg/m(2) in combination with capecitabine-oxaliplatin (XELOX).


RESULTS
Median number of prior treatment lines was 3 in the low-dose and 2 in the high-dose cohort. Overall, 21 patients had been pretreated with oxaliplatin-based regimens. No grade 3-4 NGR-hTNF-related toxicities were observed. Grade 1-2 chills were reported in 43% and 40% of cycles in the low-dose and high-dose cohorts, respectively. In the low-dose cohort, one patient achieved a partial response and five had stable disease for a median of 4.6 months. In the high-dose cohort, six patients had stable disease for a median of 3.6 months. Three-month progression-free survival (PFS) rates were 50% and 33% in the low-dose and high-dose cohort, respectively. Three patients in low-dose cohort experienced PFS longer than PFS on last prior therapy.


CONCLUSIONS
Both NGR-hTNF doses were safely combined with XELOX in pretreated CRC patients. Hint of activity was apparent only with low-dose NGR-hTNF.
Mammoliti
S
S
Medical Oncology Unit, Ospedale San Martino, Genoa.
Andretta
V
V
Medical Oncology Unit, Ospedale San Martino, Genoa.
Bennicelli
E
E
Medical Oncology Unit, Ospedale San Martino, Genoa.
Caprioni
F
F
Medical Oncology Unit, Ospedale San Martino, Genoa.
Comandini
D
D
Medical Oncology Unit, Ospedale San Martino, Genoa.
Fornarini
G
G
Medical Oncology Unit, Ospedale San Martino, Genoa.
Guglielmi
A
A
Medical Oncology Unit, Ospedale San Martino, Genoa.
Pessino
A
A
Medical Oncology Unit, Ospedale San Martino, Genoa.
Sciallero
S
S
Medical Oncology Unit, Ospedale San Martino, Genoa.
Sobrero
A F
AF
Medical Oncology Unit, Ospedale San Martino, Genoa.
Mazzola
G
G
Clinical Development, MolMed, Milan.
Lambiase
A
A
Clinical Development, MolMed, Milan.
Bordignon
C
C
Clinical Development, MolMed, Milan; Hematology, Università Vita-Salute San Raffaele, Milan, Italy. Electronic address: claudio.bordignon@hsr.it.
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D000077150:Oxaliplatin; D010071:Oxaloacetates; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D016879:Salvage Therapy; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use*
D009944:Organoplatinum Compounds; D010071:Oxaloacetates; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha; C464839:tumor necrosis factor-alpha, CNGRC fusion protein, human; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil