Faculty Collaboration Database

A phase I trial of imexon, a pro-oxidant, in combination with docetaxel for the treatment of patients with advanced breast, non-small cell lung and prostate cancer. Invest New Drugs 2010 Oct;28(5):634-40

Date

06/06/2009

Pubmed ID

19499186

DOI

10.1007/s10637-009-9273-1

Scopus ID

2-s2.0-77956056306 (requires institutional sign-in at Scopus site)   31 Citations

Abstract

PURPOSE: Imexon is an iminopyrrolidone that induces apoptosis and has synergistic activity with docetaxel in preclinical models. This trial was designed to establish the maximum tolerated dose (MTD) of imexon given with docetaxel in breast, prostate and non-small cell lung cancer (NSCLC).

PATIENTS AND METHODS: 34 patients received protocol therapy. 26 patients received escalating doses of imexon given intravenously over 60 min on days 1-5 every 21 days. Docetaxel was administered intravenously at a fixed dose of 75 mg/m(2) immediately following imexon on day 1 every 21 days. A 3+3 design was used with eight additional patients treated at MTD. Response was measured using RECIST.

RESULTS: Seven dose levels of imexon were evaluated (390 mg/m(2) to 1,700 mg/m(2)). The MTD was imexon 1,300 mg/m(2) IV on days 1-5 in combination with docetaxel. Dose limiting toxicities were grade 3 non-cardiac chest pain and grade 3 diarrhea. Activity was seen in 4 patients [2 partial responses (NSCLC (PR=1), prostate cancer (PR=1)), 2 minor responses (MR=breast, NSCLC)]. Eleven patients had stable disease by RECIST (including the patients with MR; prostate cancer=6, NSCLC=3). Six (one with breast cancer, two with prostate cancer and three with NSCLC) demonstrated stable disease (SD) for > or = 3 months.

CONCLUSION: The MTD of combination therapy is imexon 1,300 mg/m(2) IV on days 1-5 with docetaxel 75 mg/m(2) IV on day 1 of a 21 day treatment cycle. Demonstrated responses warrant further investigation in phase II trials of which a phase II trial in NSCLC is planned.

Author List

Moulder S, Dhillon N, Ng C, Hong D, Wheler J, Naing A, Tse S, La Paglia A, Dorr R, Hersh E, Boytim M, Kurzrock R

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Breast Neoplasms
Carcinoma, Non-Small-Cell Lung
Demography
Female
Hexanones
Humans
Lung Neoplasms
Male
Middle Aged
Neoplasm Staging
Prostatic Neoplasms
Reactive Oxygen Species
Taxoids
Treatment Outcome