Dataset Information

Phase 1 study of Z-endoxifen in patients with advanced gynecologic, desmoid, and hormone receptor-positive solid tumors.

ABSTRACT:

Background

Differential responses to tamoxifen may be due to inter-patient variability in tamoxifen metabolism into pharmacologically active Z-endoxifen. Z-endoxifen administration was anticipated to bypass these variations, increasing active drug levels, and potentially benefitting patients responding sub-optimally to tamoxifen.

Materials and methods

Patients with treatment-refractory gynecologic malignancies, desmoid tumors, or hormone receptor-positive solid tumors took oral Z-endoxifen daily with a 3+3 phase 1 dose escalation format over 8 dose levels (DLs). Safety, pharmacokinetics/pharmacodynamics, and clinical outcomes were evaluated.

Results

Thirty-four of 40 patients were evaluable. No maximum tolerated dose was established. DL8, 360 mg/day, was used for the expansion phase and is higher than doses administered in any previous study; it also yielded higher plasma Z-endoxifen concentrations. Three patients had partial responses and 8 had prolonged stable disease (? 6 cycles); 44.4% (8/18) of patients at dose levels 6-8 achieved one of these outcomes. Six patients who progressed after tamoxifen therapy experienced partial response or stable disease for ? 6 cycles with Z-endoxifen; one with desmoid tumor remains on study after 62 cycles (nearly 5 years).

Conclusions

Evidence of antitumor activity and prolonged stable disease are achieved with Z-endoxifen despite prior tamoxifen therapy, supporting further study of Z-endoxifen, particularly in patients with desmoid tumors.

SUBMITTER: Takebe N

PROVIDER: S-EPMC7899551 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Publications

Phase 1 study of Z-endoxifen in patients with advanced gynecologic, desmoid, and hormone receptor-positive solid tumors.

Takebe Naoko N Coyne Geraldine O'Sullivan GO Kummar Shivaani S Collins Jerry J Reid Joel M JM Piekarz Richard R Moore Nancy N Juwara Lamin L Johnson Barry C BC Bishop Rachel R Lin Frank I FI Mena Esther E Choyke Peter L PL Lindenberg M Liza ML Rubinstein Larry V LV Bonilla Cecilia Monge CM Goetz Matthew P MP Ames Matthew M MM McGovern Renee M RM Streicher Howard H Covey Joseph M JM Doroshow James H JH Chen Alice P AP

Oncotarget 20210216 4

<h4>Background</h4>Differential responses to tamoxifen may be due to inter-patient variability in tamoxifen metabolism into pharmacologically active Z-endoxifen. Z-endoxifen administration was anticipated to bypass these variations, increasing active drug levels, and potentially benefitting patients responding sub-optimally to tamoxifen.<h4>Materials and methods</h4>Patients with treatment-refractory gynecologic malignancies, desmoid tumors, or hormone receptor-positive solid tumors took oral Z- ...[more]

PMID: 33659039

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Dataset Information

Phase 1 study of Z-endoxifen in patients with advanced gynecologic, desmoid, and hormone receptor-positive solid tumors.

Background

Materials and methods

Results

Conclusions

Publications

Phase 1 study of Z-endoxifen in patients with advanced gynecologic, desmoid, and hormone receptor-positive solid tumors.

Similar Datasets

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