Anticancer agent – NGR-hTNF
Italian company MolMed is investigating NGR-hTNF, a conjugate of the targeting tripeptide and human TNF, as a potential way of increasing the effectiveness of chemotherapeutic drugs in a variety of different solid tumours.
Targeting the blood vessels that grow to supply a tumour is an important strategy in cancer chemotherapy. Several peptides, both cyclic and linear, that selectively target tumour vasculature have been identified, all of which contain an asparagine–glycine–arginine moiety. If this is then conjugated to the cytokine human tumour necrosis factor a, which has potent antitumour effects and increases the penetration of chemotherapy drugs by affecting the endothelium, it could be used to target the TNF-a more effectively to the tumour’s vasculature.
Italian company MolMed is investigating NGR-hTNF, a conjugate of the targeting tripeptide and human TNF, as a potential way of increasing the effectiveness of chemotherapeutic drugs in a variety of different solid tumours.1
Three Phase II trials were reported at this year’s ASCO meeting in Chicago. In one, 82 patients with stage IIIb or IV non-small cell lung cancer were randomly assigned to receive cisplatin plus either gemcitabine or pemetrexed either with or without 0.8µg/m2 NGR-hTNF every three weeks for up to six cycles.2 Of the 62 patients evaluated at the time, those given the combination were more than twice as likely to have experienced progression-free survival, with two partial responses in the combination group compared with one in the control.
The second trial was in 37 patients with relapsed ovarian cancer.3 All had failed at least one prior platinum–taxane regimen. They were given 0.8µg/m2 of NGR-hTNF plus 60mg/m2 doxorubicin every three weeks. Doxorubicin was given for up to eight cycles, and the new agent until disease progression occurred. No increase in doxorubicin related toxicities were seen, nor any grade 3–4 toxicities related to the new agent. Six achieved a partial response, and by the end of the trial 17 had experienced stable disease. The median progression-free survival was five months.
Relapsed small cell lung cancer was the focus of the third.4 In this trial, 28 patients who had relapsed after up to three prior treatment regimens were given 0.8µg/m2 plus 75mg/m2 doxorubicin every three weeks until progression occurred. In all, six achieved a partial response, and nine stable disease, with a medial progression free survival of 3.2 months. Again, no grade 3–4 toxicities relating to NGR-hTNF were seen, and the most common side-effect was transient chill. Further trials are under way.
1. A. Corti et al. Blood 2008, 112, 2628
2. V. Gregorc et al. J. Clin. Oncol. 2011, 29 (Suppl.), Abst 7568
3. G. Scambia et al. J. Clin. Oncol. 2011, 29 (Suppl.), Abst 5022
4. M.G. Vigano et al. J. Clin. Oncol. 2011, 29 (Suppl.), Abst 7077
