The University of Southampton
University of Southampton Institutional Repository

A phase I and pharmacokinetic study of lapatinib in combination with letrozole in patients with advanced cancer

A phase I and pharmacokinetic study of lapatinib in combination with letrozole in patients with advanced cancer
A phase I and pharmacokinetic study of lapatinib in combination with letrozole in patients with advanced cancer
Purpose: The main objectives of this phase I and pharmacokinetic, open-label study were to determine the optimally tolerated regimen (OTR), safety, pharmacokinetics, and clinical activity of lapatinib in combination with letrozole in patients with advanced solid malignancies.
Experimental Design: Patients with advanced breast cancer with immunohistochemically detectable estrogen or progesterone receptors or other cancers were eligible. Doses of lapatinib were escalated in cohorts of three subjects from 1,250 to a maximum of 1,500 mg/d based on dose-limiting toxicities in the first treatment cycle. The letrozole dose was fixed at 2.5 mg/d. Additional patients were enrolled at the OTR dose level to further evaluate safety and for pharmacokinetic analyses.
Results: Thirty-nine patients were enrolled in the study: 12 in the dose-escalation group, 7 in the OTR safety group, and 20 in the pharmacokinetic group. The OTR dose level was identified as 1,500 mg/d lapatinib and 2.5 mg/d letrozole. The most common (>25% of patients) drug-related adverse events were diarrhea (77%), rash (62%), nausea (46%), and fatigue (26%). No significant differences were observed in the pharmacokinetic variables (Cmax and AUC) of lapatinib and letrozole when coadministered compared with single-agent administration. One patient with endometrial cancer had a confirmed partial response.
Conclusions: Clinically relevant doses of lapatinib in combination with letrozole were well tolerated and did not result in a pharmacokinetic interaction, and clinical antitumor activity was observed.
1078-0432
4484-4490
Chu, Quincy S.C.
0efcf273-d391-4d73-a4be-abfa4be6e371
Cianfrocca, Mary E.
cee973df-a1da-4ee2-882e-bd7f88a26134
Goldstein, Lori J.
b59de6eb-2247-4773-bddf-5e0ecb28ed67
Gale, Meg
8185647c-9ba2-4d45-9111-06cae2203fca
Murray, Nicholas
181c1b77-e1d3-4fa5-9ef8-52c73025ab9d
Loftiss, Jill
30f336c7-10ce-4fa8-a1ae-e82687e56af4
Arya, Nikita
e41404cf-d378-4e7c-922a-be971b04b3a1
Koch, Kevin M.
6065e4cb-4f93-4f85-b503-7784e1263d8b
Pandite, Lini
1ed11dd9-3e71-4866-98fe-039e1ecb21ee
Fleming, Ronald A.
7b9be97d-179c-41ec-b324-4fe151095c85
Paul, Elaine
bce1f585-1d6a-4e9b-9f2f-a3415e62979f
Rowinsky, Eric K.
5020c54e-6a9e-4c85-8e6b-93244699d73f
Chu, Quincy S.C.
0efcf273-d391-4d73-a4be-abfa4be6e371
Cianfrocca, Mary E.
cee973df-a1da-4ee2-882e-bd7f88a26134
Goldstein, Lori J.
b59de6eb-2247-4773-bddf-5e0ecb28ed67
Gale, Meg
8185647c-9ba2-4d45-9111-06cae2203fca
Murray, Nicholas
181c1b77-e1d3-4fa5-9ef8-52c73025ab9d
Loftiss, Jill
30f336c7-10ce-4fa8-a1ae-e82687e56af4
Arya, Nikita
e41404cf-d378-4e7c-922a-be971b04b3a1
Koch, Kevin M.
6065e4cb-4f93-4f85-b503-7784e1263d8b
Pandite, Lini
1ed11dd9-3e71-4866-98fe-039e1ecb21ee
Fleming, Ronald A.
7b9be97d-179c-41ec-b324-4fe151095c85
Paul, Elaine
bce1f585-1d6a-4e9b-9f2f-a3415e62979f
Rowinsky, Eric K.
5020c54e-6a9e-4c85-8e6b-93244699d73f

Chu, Quincy S.C., Cianfrocca, Mary E., Goldstein, Lori J., Gale, Meg, Murray, Nicholas, Loftiss, Jill, Arya, Nikita, Koch, Kevin M., Pandite, Lini, Fleming, Ronald A., Paul, Elaine and Rowinsky, Eric K. (2008) A phase I and pharmacokinetic study of lapatinib in combination with letrozole in patients with advanced cancer. Clinical Cancer Research, 14 (14), 4484-4490. (doi:10.1158/1078-0432.CCR-07-4417).

Record type: Article

Abstract

Purpose: The main objectives of this phase I and pharmacokinetic, open-label study were to determine the optimally tolerated regimen (OTR), safety, pharmacokinetics, and clinical activity of lapatinib in combination with letrozole in patients with advanced solid malignancies.
Experimental Design: Patients with advanced breast cancer with immunohistochemically detectable estrogen or progesterone receptors or other cancers were eligible. Doses of lapatinib were escalated in cohorts of three subjects from 1,250 to a maximum of 1,500 mg/d based on dose-limiting toxicities in the first treatment cycle. The letrozole dose was fixed at 2.5 mg/d. Additional patients were enrolled at the OTR dose level to further evaluate safety and for pharmacokinetic analyses.
Results: Thirty-nine patients were enrolled in the study: 12 in the dose-escalation group, 7 in the OTR safety group, and 20 in the pharmacokinetic group. The OTR dose level was identified as 1,500 mg/d lapatinib and 2.5 mg/d letrozole. The most common (>25% of patients) drug-related adverse events were diarrhea (77%), rash (62%), nausea (46%), and fatigue (26%). No significant differences were observed in the pharmacokinetic variables (Cmax and AUC) of lapatinib and letrozole when coadministered compared with single-agent administration. One patient with endometrial cancer had a confirmed partial response.
Conclusions: Clinically relevant doses of lapatinib in combination with letrozole were well tolerated and did not result in a pharmacokinetic interaction, and clinical antitumor activity was observed.

Full text not available from this repository.

More information

Published date: 15 July 2008

Identifiers

Local EPrints ID: 79465
URI: https://eprints.soton.ac.uk/id/eprint/79465
ISSN: 1078-0432
PURE UUID: 1043499d-06c0-4cd1-980e-9468cbf556d0

Catalogue record

Date deposited: 16 Mar 2010
Last modified: 18 Jul 2017 23:17

Export record

Altmetrics

Contributors

Author: Quincy S.C. Chu
Author: Mary E. Cianfrocca
Author: Lori J. Goldstein
Author: Meg Gale
Author: Nicholas Murray
Author: Jill Loftiss
Author: Nikita Arya
Author: Kevin M. Koch
Author: Lini Pandite
Author: Ronald A. Fleming
Author: Elaine Paul
Author: Eric K. Rowinsky

University divisions

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of https://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×