A Phase 1 Dose Escalation of Lapatinib and Paclitaxel in Recurrent Ovarian Cancer

Connie D Cao; Joseph Robert McCorkle; Donglin Yan; Hoda Saghaeiannejad Esfahani; Rani Jayswal; Dava Piecoro; Ning Li; Lauren A Baldwin; Rachel W Miller; Christopher P Desimone; Charles S Dietrich; Frederick R Ueland; Jill M Kolesar

doi:10.3390/cancers18040626

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A Phase 1 Dose Escalation of Lapatinib and Paclitaxel in Recurrent Ovarian Cancer

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A Phase 1 Dose Escalation of Lapatinib and Paclitaxel in Recurrent Ovarian Cancer

Connie D Cao, Joseph Robert McCorkle, Donglin Yan, Hoda Saghaeiannejad Esfahani, Rani Jayswal, Dava Piecoro, Ning Li, Lauren A Baldwin, Rachel W Miller, Christopher P Desimone, …

Cancers, Vol.18(4), 626

02/14/2026

DOI: 10.3390/cancers18040626

PMID: 41749879

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Abstract

The development of ABCB1-mediated resistance limits the clinical efficacy of paclitaxel. Lapatinib is a small-molecule reversible tyrosine kinase and ABCB1 inhibitor that could prevent resistance. Our objective was to determine a recommended phase 2 dose (RP2D) of the combination of paclitaxel and lapatinib. A phase 1 dose-escalation study utilizing a Bayesian optimal interval (BOIN) design in recurrent ovarian cancer patients was conducted. Patients were pretreated with pulsed lapatinib in the 48 h preceding weekly paclitaxel (80 mg/m ) in 28-day cycles for up to three cycles. We evaluated three lapatinib doses, escalating from 750 to 2000 mg orally twice daily. Sixteen patients were eligible and evaluable for efficacy and toxicity. Patients received a median of three prior therapies. Three patients were treated at dose level 1, six at dose level 2, and seven at dose level 3. There was one dose-limiting toxicity (DLT) in dose level 2 (diarrhea) and another in dose level 3 (neutropenia), with a posterior DLT estimate of 0.17, 95% credible interval of (0.01, 0.53) for dose level 3 based on isotonic regression. The most common grade 1-2 adverse effects were diarrhea (87.5%), leukopenia (56.3%), and anemia (50%). One (6.25%) patient had a complete response, and seven (43.75%) patients had partial responses for an overall response rate (ORR) of 50%. The clinical responses are supported by a significant decreasing trend in CA 125 over six cycles ( = 0.0001). Among the seven patients treated at the RP2D, the ORR was 71.4%. The combination of paclitaxel and lapatinib was safe and demonstrated an efficacy signal. The RP2D was weekly paclitaxel 80 mg/m combined with lapatinib 2000 mg twice daily two days before the paclitaxel dose. This trial was registered at ClinicalTrials.gov ID: NCT04608409.

lapatinib

paclitaxel

recurrent ovarian cancer

Details

Title: Subtitle: A Phase 1 Dose Escalation of Lapatinib and Paclitaxel in Recurrent Ovarian Cancer
Creators: Connie D Cao - University of Kentucky
Joseph Robert McCorkle - Markey Cancer Center
Donglin Yan - University of Kentucky
Hoda Saghaeiannejad Esfahani - University of Kentucky
Rani Jayswal - University of Kentucky
Dava Piecoro - Markey Cancer Center
Ning Li - University of Kentucky
Lauren A Baldwin - University of Kentucky
Rachel W Miller - University of Kentucky
Christopher P Desimone - University of Kentucky
Charles S Dietrich - University of Kentucky
Frederick R Ueland - University of Kentucky
Jill M Kolesar - University of Iowa
Resource Type: Journal article
Publication Details: Cancers, Vol.18(4), 626
DOI: 10.3390/cancers18040626
PMID: 41749879
NLM abbreviation: Cancers (Basel)
ISSN: 2072-6694
eISSN: 2072-6694
Publisher: MDPI
Grant note: T32 CA160003 / NCI NIH HHS P30CA177558 / NCI NIH HHS
Language: English
Date published: 02/14/2026
Academic Unit: Pharmacy; Pharmaceutical Sciences and Experimental Therapeutics; Obstetrics and Gynecology
Record Identifier: 9985139313302771

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