A phase I study of cilengitide and paclitaxel in patients with advanced solid tumors.

Abstract

PURPOSE:

Cilengitide is a potent and selective inhibitor of the integrins αvβ3 and αvβ5. The primary objective of this phase I clinical trial was to establish the maximum tolerated dose and determine safety/tolerability of cilengitide in combination with paclitaxel in patients with advanced solid tumors. Secondary objectives included the evaluation of the preliminary clinical outcomes.

PATIENTS AND METHODS:

Patients with advanced solid tumors experiencing disease progression on standard treatment were assigned to two different dose levels of cilengitide (2000 mg intravenously once or twice weekly) in combination with fixed-dose, weekly paclitaxel (90 mg/m2 intravenously).

RESULTS:

Twelve evaluable patients were treated per protocol. A single dose limiting toxicity (DLT) of grade 4 neutropenia was observed at the starting dose level of once weekly cilengitide. There were no grade ≥3 adverse events that occurred with >10% frequency. One patient achieved a partial response to therapy. Five patients experienced stable disease as best response, 3 of which discontinued study participation due to progressive, peripheral neuropathy.

CONCLUSIONS:

Cilengitide in combination with paclitaxel was well tolerated. Antitumor activity was observed. The recommended phase II dose is twice weekly cilengitide (2000 mg) with weekly paclitaxel (90 mg/m2). Further studies evaluating drugs that target this pathway are warranted.

• Authors: Tufia Haddad, Rui Qin, Ruth Lupu, Daniel Satele, Matthew Eadens, Matthew P Goetz, Charles Erlichman, Julian Molina
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 79 Issue 6 Pg. 1221-1227 (Jun 2017) ISSN: 1432-0843 [Electronic] Germany
• PMID: 28477227 (Publication Type: Clinical Trial, Phase I, Journal Article)

Chemical References

• Angiogenesis Inhibitors
• Antineoplastic Agents, Phytogenic
• Integrin alphaVbeta3
• Receptors, Vitronectin
• Snake Venoms
• integrin alphaVbeta5
• Cilengitide
• Paclitaxel

Topics

• Adult
• Aged
• Angiogenesis Inhibitors (administration & dosage)
• Antineoplastic Agents, Phytogenic (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Dose-Response Relationship, Drug
• Female
• Humans
• Integrin alphaVbeta3 (antagonists & inhibitors)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Neoplasms (drug therapy)
• Neutropenia (chemically induced)
• Paclitaxel (administration & dosage)
• Peripheral Nervous System Diseases (chemically induced)
• Receptors, Vitronectin (antagonists & inhibitors)
• Snake Venoms (administration & dosage)
• Treatment Outcome