Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer

Don S Dizon; Lars Damstrup; Neil J Finkler; Ulrik Lassen; Paul Celano; Ros Glasspool; Elizabeth Crowley; Henri S Lichenstein; Poul Knoblach; Richard T Penson

doi:10.1097/igc.0b013e31825736fd

Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer

Don S Dizon, Lars Damstrup, Neil J Finkler, Ulrik Lassen, Paul Celano, Ros Glasspool, Elizabeth Crowley, Henri S Lichenstein, Poul Knoblach, Richard T Penson

Institut for Klinisk Medicin

57 Citationer (Scopus)

Abstract

Background: Preclinical data show that belinostat (Bel) is synergistic with carboplatin and paclitaxel in ovarian cancer. To further evaluate the clinical activity of belinostat, carboplatin, and paclitaxel (BelCaP), a phase 1b/2 study was performed, with an exploratory phase 2 expansion planned specifically for women with recurrent epithelial ovarian cancer (EOC). Methods: Thirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m ² daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m ² given on day 3 of a 21-day cycle. The primary end point was overall response rate (ORR), using a Simon 2 stage design. Results: The median age was 60 years (range, 39-80 years), and patients had received a median of 3 prior regimens (range, 1-4). Fifty-four percent had received more than two prior platinum-based combinations, sixteen patients (46%) had primary platinum-resistant disease, whereas 19 patients (54%) recurred within 6 months of their most recent platinum treatment. The median number of cycles of BelCaP administered was 6 (range, 1-23). Three patients had a complete response, and 12 had a partial response, for an ORR of 43% (95% confidence interval, 26%Y61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drugrelated adverse events related to BelCaP were nausea (83%), fatigue (74%), vomiting (63%), alopecia (57%), and diarrhea (37%). With a median follow-up of 4 months (range, 0-23.3 months), 6-month progression-free survival is 48% (95% confidence interval, 31%Y66%). Median overall survival was not reached during study follow-up. Conclusions: Belinostat, carboplatin, and paclitaxel combinedwas reasonablywell tolerated and demonstrated clinical benefit in heavily-pretreated patients with EOC. The addition of belinostat to this platinum-based regimen represents a novel approach to EOC therapy and warrants further exploration.

Originalsprog	Engelsk
Tidsskrift	International Journal of Gynecological Cancer
Vol/bind	22
Udgave nummer	6
Sider (fra-til)	979-86
Antal sider	8
ISSN	1048-891X
DOI	https://doi.org/10.1097/igc.0b013e31825736fd
Status	Udgivet - jul. 2012

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10.1097/igc.0b013e31825736fd

https://pdfs.journals.lww.com/ijgc/2012/07000/Phase_II_Activity_of_Belinostat__PXD_101_,.12.pdf?token=method|ExpireAbsolute;source|Journals;ttl|1541415497120;payload|mY8D3u1TCCsNvP5E421JYK6N6XICDamxByyYpaNzk7FKjTaa1Yz22MivkHZqjGP4kdS2v0J76WGAnHACH69s21Csk0OpQi3YbjEMdSoz2UhVybFqQxA7lKwSUlA502zQZr96TQRwhVlocEp/sJ586aVbcBFlltKNKo+tbuMfL73hiPqJliudqs17cHeLcLbV/CqjlP3IO0jGHlHQtJWcICDdAyGJMnpi6RlbEJaRheGeh5z5uvqz3FLHgPKVXJzdlYsHmeqGyToAv7nTC5VmbiJqGZnqzOHIpm5vyz4QrSM=;hash|PByCoZqG/2mNA7WYP1AoqQ==

Citationsformater

Dizon, D. S., Damstrup, L., Finkler, N. J., Lassen, U., Celano, P., Glasspool, R., Crowley, E., Lichenstein, H. S., Knoblach, P., & Penson, R. T. (2012). Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer. International Journal of Gynecological Cancer, 22(6), 979-86. https://doi.org/10.1097/igc.0b013e31825736fd

Dizon, DS, Damstrup, L, Finkler, NJ, Lassen, U, Celano, P, Glasspool, R, Crowley, E, Lichenstein, HS, Knoblach, P & Penson, RT 2012, 'Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer', International Journal of Gynecological Cancer, bind 22, nr. 6, s. 979-86. https://doi.org/10.1097/igc.0b013e31825736fd

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title = "Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer",

abstract = "Background: Preclinical data show that belinostat (Bel) is synergistic with carboplatin and paclitaxel in ovarian cancer. To further evaluate the clinical activity of belinostat, carboplatin, and paclitaxel (BelCaP), a phase 1b/2 study was performed, with an exploratory phase 2 expansion planned specifically for women with recurrent epithelial ovarian cancer (EOC). Methods: Thirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m 2 daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m 2 given on day 3 of a 21-day cycle. The primary end point was overall response rate (ORR), using a Simon 2 stage design. Results: The median age was 60 years (range, 39-80 years), and patients had received a median of 3 prior regimens (range, 1-4). Fifty-four percent had received more than two prior platinum-based combinations, sixteen patients (46%) had primary platinum-resistant disease, whereas 19 patients (54%) recurred within 6 months of their most recent platinum treatment. The median number of cycles of BelCaP administered was 6 (range, 1-23). Three patients had a complete response, and 12 had a partial response, for an ORR of 43% (95% confidence interval, 26%Y61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drugrelated adverse events related to BelCaP were nausea (83%), fatigue (74%), vomiting (63%), alopecia (57%), and diarrhea (37%). With a median follow-up of 4 months (range, 0-23.3 months), 6-month progression-free survival is 48% (95% confidence interval, 31%Y66%). Median overall survival was not reached during study follow-up. Conclusions: Belinostat, carboplatin, and paclitaxel combinedwas reasonablywell tolerated and demonstrated clinical benefit in heavily-pretreated patients with EOC. The addition of belinostat to this platinum-based regimen represents a novel approach to EOC therapy and warrants further exploration.",

keywords = "Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Phytogenic, Antineoplastic Combined Chemotherapy Protocols, Carboplatin, Carcinoma, Female, Humans, Hydroxamic Acids, Middle Aged, Neoplasm Recurrence, Local, Ovarian Neoplasms, Paclitaxel, Sulfonamides, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't",

author = "Dizon, {Don S} and Lars Damstrup and Finkler, {Neil J} and Ulrik Lassen and Paul Celano and Ros Glasspool and Elizabeth Crowley and Lichenstein, {Henri S} and Poul Knoblach and Penson, {Richard T}",

year = "2012",

month = jul,

doi = "10.1097/igc.0b013e31825736fd",

language = "English",

volume = "22",

pages = "979--86",

journal = "International Journal of Gynecological Cancer",

issn = "1048-891X",

publisher = "Lippincott Williams & Wilkins, Ltd.",

number = "6",

}

TY - JOUR

T1 - Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer

AU - Dizon, Don S

AU - Damstrup, Lars

AU - Finkler, Neil J

AU - Lassen, Ulrik

AU - Celano, Paul

AU - Glasspool, Ros

AU - Crowley, Elizabeth

AU - Lichenstein, Henri S

AU - Knoblach, Poul

AU - Penson, Richard T

PY - 2012/7

Y1 - 2012/7

N2 - Background: Preclinical data show that belinostat (Bel) is synergistic with carboplatin and paclitaxel in ovarian cancer. To further evaluate the clinical activity of belinostat, carboplatin, and paclitaxel (BelCaP), a phase 1b/2 study was performed, with an exploratory phase 2 expansion planned specifically for women with recurrent epithelial ovarian cancer (EOC). Methods: Thirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m 2 daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m 2 given on day 3 of a 21-day cycle. The primary end point was overall response rate (ORR), using a Simon 2 stage design. Results: The median age was 60 years (range, 39-80 years), and patients had received a median of 3 prior regimens (range, 1-4). Fifty-four percent had received more than two prior platinum-based combinations, sixteen patients (46%) had primary platinum-resistant disease, whereas 19 patients (54%) recurred within 6 months of their most recent platinum treatment. The median number of cycles of BelCaP administered was 6 (range, 1-23). Three patients had a complete response, and 12 had a partial response, for an ORR of 43% (95% confidence interval, 26%Y61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drugrelated adverse events related to BelCaP were nausea (83%), fatigue (74%), vomiting (63%), alopecia (57%), and diarrhea (37%). With a median follow-up of 4 months (range, 0-23.3 months), 6-month progression-free survival is 48% (95% confidence interval, 31%Y66%). Median overall survival was not reached during study follow-up. Conclusions: Belinostat, carboplatin, and paclitaxel combinedwas reasonablywell tolerated and demonstrated clinical benefit in heavily-pretreated patients with EOC. The addition of belinostat to this platinum-based regimen represents a novel approach to EOC therapy and warrants further exploration.

AB - Background: Preclinical data show that belinostat (Bel) is synergistic with carboplatin and paclitaxel in ovarian cancer. To further evaluate the clinical activity of belinostat, carboplatin, and paclitaxel (BelCaP), a phase 1b/2 study was performed, with an exploratory phase 2 expansion planned specifically for women with recurrent epithelial ovarian cancer (EOC). Methods: Thirty-five women were treated on the phase 2 expansion cohort. BelCap was given as follows: belinostat, 1000 mg/m 2 daily for 5 days with carboplatin, AUC 5; and paclitaxel, 175 mg/m 2 given on day 3 of a 21-day cycle. The primary end point was overall response rate (ORR), using a Simon 2 stage design. Results: The median age was 60 years (range, 39-80 years), and patients had received a median of 3 prior regimens (range, 1-4). Fifty-four percent had received more than two prior platinum-based combinations, sixteen patients (46%) had primary platinum-resistant disease, whereas 19 patients (54%) recurred within 6 months of their most recent platinum treatment. The median number of cycles of BelCaP administered was 6 (range, 1-23). Three patients had a complete response, and 12 had a partial response, for an ORR of 43% (95% confidence interval, 26%Y61%). When stratified by primary platinum status, the ORR was 44% among resistant patients and 63% among sensitive patients. The most common drugrelated adverse events related to BelCaP were nausea (83%), fatigue (74%), vomiting (63%), alopecia (57%), and diarrhea (37%). With a median follow-up of 4 months (range, 0-23.3 months), 6-month progression-free survival is 48% (95% confidence interval, 31%Y66%). Median overall survival was not reached during study follow-up. Conclusions: Belinostat, carboplatin, and paclitaxel combinedwas reasonablywell tolerated and demonstrated clinical benefit in heavily-pretreated patients with EOC. The addition of belinostat to this platinum-based regimen represents a novel approach to EOC therapy and warrants further exploration.

KW - Adult

KW - Aged

KW - Aged, 80 and over

KW - Antineoplastic Agents, Phytogenic

KW - Antineoplastic Combined Chemotherapy Protocols

KW - Carboplatin

KW - Carcinoma

KW - Female

KW - Humans

KW - Hydroxamic Acids

KW - Middle Aged

KW - Neoplasm Recurrence, Local

KW - Ovarian Neoplasms

KW - Paclitaxel

KW - Sulfonamides

KW - Clinical Trial, Phase II

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1097/igc.0b013e31825736fd

DO - 10.1097/igc.0b013e31825736fd

M3 - Journal article

C2 - 22694911

SN - 1048-891X

VL - 22

SP - 979

EP - 986

JO - International Journal of Gynecological Cancer

JF - International Journal of Gynecological Cancer

IS - 6

ER -

Phase II activity of belinostat (PXD-101), carboplatin, and paclitaxel in women with previously treated ovarian cancer

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