A Phase I and Pharmocokinetic study of Pemetrexed (Alimta) Plus Irinotecan (Camptosar) in Patients with Advanced Solid Malignancies

PURPOSE:
The main objectives of the open-label study were to determine the principal toxicities associated with the chemotherapy agents known as Alimta and Camptosar and determine the maximum tolerated dosage of the two chemotherapy agents when given together. Another primary goal was to detect what interactions the drugs have with each other and how they affect tumor activity in patients with advanced solid malignancies such as mesothelioma.

EXPERIMENTAL DESIGN:
Once every three weeks, patients received an intravenous (i.v.) infusion of Alimta for 10 minutes followed by an i.v. infusion of Camptosar for 90 minutes. In the first stage of the study, patients received heavy treatments. In the second stage of the study, patients received lighter treatments with vitamin supplements.

RESULTS:
Twenty-three patients enrolled in the first stage of the study and received heavy treatments. The maximum tolerated dose level of Alimta/Camptosar was 400/250 mg/m(2). Some patients developed severe neutropenia associated with a fever and did not receive further high dose treatments once these symptoms occurred.

In the second stage of the study, 28 were lightly treated with Alimta/Camptosar with vitamin supplements. These patients tolerated doses at a level of 500/350 mg/m(2), which reflected clinically relevant single-agent doses of both agents.

No major pharmacokinetic interactions between the agents were evident. Four patients, two patients each with colorectal cancer refractory to fluoropyrimidines and advanced mesothelioma, had partial responses.

CONCLUSIONS:
The Alimta/Camptosar regimen is well tolerated in patients with advanced solid malignancies (such as mesothelioma) at clinically relevant single-agent doses. The recommended dose level of Alimta/Camptosar for subsequent disease-directed evaluations involving lightly treated patients is 500/350 mg/m(2) every 3 weeks with vitamin supplementation.

Institute for Drug Development, Cancer Therapy, and Research Center, San Antonio, Texas, USA. erowinsky@oncodrugs.com

Authors: E.K. Rowinsky, M. Beeram, L.A. Hammond, G. Schwartz, J. DeBono, B. Forouzewsh, Q. Chu, J.E. Latz, S. Hong, W. John, B. Nguyen

National Center for Biotechnology Information. PubMed. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17255275&query_hl=1&itool=pubmed_docsum

Jan. 15, 2007. Feb. 15, 2007.

*** POSTED ON FEBRUARY 15, 2007 ***