Delta tocotrienol in recurrent ovarian cancer. A phase II trial

Caroline Brenner Thomsen, Rikke Fredslund Andersen, Karina Dahl Steffensen, Parvin Adimi, Anders Jakobsen*

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Resumé

Delta tocotrienol has anti-neoplastic activity as demonstrated in several in-vitro and in-vivo investigations. The effect relies on inhibition of different pathways. It also has antiangiogenic activity, and an additive effect to bevacizumab may be expected. The present study was a phase II trial of bevacizumab combined with tocotrienol in chemotherapy refractory ovarian cancer. The study also included analysis of circulating tumor specific HOXA9 methylated DNA (HOXA9 meth-ctDNA) during treatment. The study included 23 patients. The rate of disease stabilization was 70% with very low toxicity. The median PFS was 6.9 months and the median OS 10.9 months, which is rather high compared to the current literature. A division of the patients according to level of HOXA9 meth-ctDNA already after the first cycle of chemotherapy resulted in two groups of patients with different prognoses. Patients with an increasing level of HOXA9 meth-ctDNA had a median PFS and OS of 1.4 and 4.3 months, respectively, compared to 7.8 and 12 months in the group with stable or decreasing levels. The combination of bevacizumab and tocotrienol is potent in chemotherapy refractory ovarian cancer. The level of HOXA9 meth-ctDNA after one cycle of chemotherapy holds important prognostic information.

OriginalsprogEngelsk
TidsskriftPharmacological Research
Vol/bind141
Sider (fra-til)392-396
ISSN1043-6618
DOI
StatusUdgivet - mar. 2019

Fingeraftryk

Ovarian Neoplasms
Tocotrienols
DNA
Bevacizumab
Neoplasms

Citer dette

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title = "Delta tocotrienol in recurrent ovarian cancer. A phase II trial",
abstract = "Delta tocotrienol has anti-neoplastic activity as demonstrated in several in-vitro and in-vivo investigations. The effect relies on inhibition of different pathways. It also has antiangiogenic activity, and an additive effect to bevacizumab may be expected. The present study was a phase II trial of bevacizumab combined with tocotrienol in chemotherapy refractory ovarian cancer. The study also included analysis of circulating tumor specific HOXA9 methylated DNA (HOXA9 meth-ctDNA) during treatment. The study included 23 patients. The rate of disease stabilization was 70{\%} with very low toxicity. The median PFS was 6.9 months and the median OS 10.9 months, which is rather high compared to the current literature. A division of the patients according to level of HOXA9 meth-ctDNA already after the first cycle of chemotherapy resulted in two groups of patients with different prognoses. Patients with an increasing level of HOXA9 meth-ctDNA had a median PFS and OS of 1.4 and 4.3 months, respectively, compared to 7.8 and 12 months in the group with stable or decreasing levels. The combination of bevacizumab and tocotrienol is potent in chemotherapy refractory ovarian cancer. The level of HOXA9 meth-ctDNA after one cycle of chemotherapy holds important prognostic information.",
keywords = "Disease control, Ovarian cancer, Tocotrienol",
author = "Thomsen, {Caroline Brenner} and Andersen, {Rikke Fredslund} and Steffensen, {Karina Dahl} and Parvin Adimi and Anders Jakobsen",
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Delta tocotrienol in recurrent ovarian cancer. A phase II trial. / Thomsen, Caroline Brenner; Andersen, Rikke Fredslund; Steffensen, Karina Dahl; Adimi, Parvin; Jakobsen, Anders.

I: Pharmacological Research, Bind 141, 03.2019, s. 392-396.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Delta tocotrienol in recurrent ovarian cancer. A phase II trial

AU - Thomsen, Caroline Brenner

AU - Andersen, Rikke Fredslund

AU - Steffensen, Karina Dahl

AU - Adimi, Parvin

AU - Jakobsen, Anders

PY - 2019/3

Y1 - 2019/3

N2 - Delta tocotrienol has anti-neoplastic activity as demonstrated in several in-vitro and in-vivo investigations. The effect relies on inhibition of different pathways. It also has antiangiogenic activity, and an additive effect to bevacizumab may be expected. The present study was a phase II trial of bevacizumab combined with tocotrienol in chemotherapy refractory ovarian cancer. The study also included analysis of circulating tumor specific HOXA9 methylated DNA (HOXA9 meth-ctDNA) during treatment. The study included 23 patients. The rate of disease stabilization was 70% with very low toxicity. The median PFS was 6.9 months and the median OS 10.9 months, which is rather high compared to the current literature. A division of the patients according to level of HOXA9 meth-ctDNA already after the first cycle of chemotherapy resulted in two groups of patients with different prognoses. Patients with an increasing level of HOXA9 meth-ctDNA had a median PFS and OS of 1.4 and 4.3 months, respectively, compared to 7.8 and 12 months in the group with stable or decreasing levels. The combination of bevacizumab and tocotrienol is potent in chemotherapy refractory ovarian cancer. The level of HOXA9 meth-ctDNA after one cycle of chemotherapy holds important prognostic information.

AB - Delta tocotrienol has anti-neoplastic activity as demonstrated in several in-vitro and in-vivo investigations. The effect relies on inhibition of different pathways. It also has antiangiogenic activity, and an additive effect to bevacizumab may be expected. The present study was a phase II trial of bevacizumab combined with tocotrienol in chemotherapy refractory ovarian cancer. The study also included analysis of circulating tumor specific HOXA9 methylated DNA (HOXA9 meth-ctDNA) during treatment. The study included 23 patients. The rate of disease stabilization was 70% with very low toxicity. The median PFS was 6.9 months and the median OS 10.9 months, which is rather high compared to the current literature. A division of the patients according to level of HOXA9 meth-ctDNA already after the first cycle of chemotherapy resulted in two groups of patients with different prognoses. Patients with an increasing level of HOXA9 meth-ctDNA had a median PFS and OS of 1.4 and 4.3 months, respectively, compared to 7.8 and 12 months in the group with stable or decreasing levels. The combination of bevacizumab and tocotrienol is potent in chemotherapy refractory ovarian cancer. The level of HOXA9 meth-ctDNA after one cycle of chemotherapy holds important prognostic information.

KW - Disease control

KW - Ovarian cancer

KW - Tocotrienol

U2 - 10.1016/j.phrs.2019.01.017

DO - 10.1016/j.phrs.2019.01.017

M3 - Journal article

VL - 141

SP - 392

EP - 396

JO - Pharmacological Research

JF - Pharmacological Research

SN - 1043-6618

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