Therapeutic index by combination of adriamycin and docetaxel depends on dosing time in mice

Mayumi Tabuchi, Hideto To, Hiromi Sakaguchi, Naho Goto, Ayako Takeuchi, Shun Higuchi, Shigehiro Ohdo

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Although the combination of adriamycin and docetaxel showed a better cure rate against metastatic breast cancer, severe myelosuppression and cardiotoxicity were dose-limiting factors. The purpose of this study was to establish a suitable dosing schedule, based on a chronopharmacologic approach, to relieve severe adverse effects. In experiment 1, adriamycin or docetaxel was injected i.p. at 2, 6, 10, 14, 18, or 22 hours after light onset (HALO) to estimate toxicities. In experiment 2, the dosing time dependency of toxicity and pharmacokinetics were assessed in the combination of adriamycin and docetaxel. In addition, G2-M phase in myelocyte cells was determined in nontreated mice. Adverse effects caused by adriamycin were shown to be the worst at 2 HALO and the best at 14 HALO. On the other hand, docetaxel-induced adverse effects were more severe at 14 HALO than at 2 HALO. In the combination study, the D(2)-A(14) group, in which docetaxel was administered at 2 HALO followed by adriamycin at 14 HALO, showed the most toxicity relief of all the treated groups. In the pharmacokinetic study, the dosing time dependency of toxicities was not related to the daily variation of pharmacokinetics of adriamycin and docetaxel. A significant 24-hour rhythm of G2-M phase distribution was found in myelocyte cells of nontreated mice. The daily variation of leukopenia caused by docetaxel corresponded to the 24-hour rhythm of G 2-M phase distribution. These findings reveal that the therapeutic index of the combined chemotherapy can be improved by administering adriamycin and docetaxel at the time when the most adverse effects are relieved in each drug.

Original languageEnglish
Pages (from-to)8448-8454
Number of pages7
JournalCancer Research
Volume65
Issue number18
DOIs
Publication statusPublished - Sep 15 2005

Fingerprint

docetaxel
Doxorubicin
Light
Cell Division
Granulocyte Precursor Cells
Pharmacokinetics
G2 Phase
Therapeutics
Leukopenia

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Therapeutic index by combination of adriamycin and docetaxel depends on dosing time in mice. / Tabuchi, Mayumi; To, Hideto; Sakaguchi, Hiromi; Goto, Naho; Takeuchi, Ayako; Higuchi, Shun; Ohdo, Shigehiro.

In: Cancer Research, Vol. 65, No. 18, 15.09.2005, p. 8448-8454.

Research output: Contribution to journalArticle

Tabuchi, M, To, H, Sakaguchi, H, Goto, N, Takeuchi, A, Higuchi, S & Ohdo, S 2005, 'Therapeutic index by combination of adriamycin and docetaxel depends on dosing time in mice', Cancer Research, vol. 65, no. 18, pp. 8448-8454. https://doi.org/10.1158/0008-5472.CAN-05-1161
Tabuchi M, To H, Sakaguchi H, Goto N, Takeuchi A, Higuchi S et al. Therapeutic index by combination of adriamycin and docetaxel depends on dosing time in mice. Cancer Research. 2005 Sep 15;65(18):8448-8454. https://doi.org/10.1158/0008-5472.CAN-05-1161
Tabuchi, Mayumi ; To, Hideto ; Sakaguchi, Hiromi ; Goto, Naho ; Takeuchi, Ayako ; Higuchi, Shun ; Ohdo, Shigehiro. / Therapeutic index by combination of adriamycin and docetaxel depends on dosing time in mice. In: Cancer Research. 2005 ; Vol. 65, No. 18. pp. 8448-8454.
@article{fba3cb177412416796cd546cf6423318,
title = "Therapeutic index by combination of adriamycin and docetaxel depends on dosing time in mice",
abstract = "Although the combination of adriamycin and docetaxel showed a better cure rate against metastatic breast cancer, severe myelosuppression and cardiotoxicity were dose-limiting factors. The purpose of this study was to establish a suitable dosing schedule, based on a chronopharmacologic approach, to relieve severe adverse effects. In experiment 1, adriamycin or docetaxel was injected i.p. at 2, 6, 10, 14, 18, or 22 hours after light onset (HALO) to estimate toxicities. In experiment 2, the dosing time dependency of toxicity and pharmacokinetics were assessed in the combination of adriamycin and docetaxel. In addition, G2-M phase in myelocyte cells was determined in nontreated mice. Adverse effects caused by adriamycin were shown to be the worst at 2 HALO and the best at 14 HALO. On the other hand, docetaxel-induced adverse effects were more severe at 14 HALO than at 2 HALO. In the combination study, the D(2)-A(14) group, in which docetaxel was administered at 2 HALO followed by adriamycin at 14 HALO, showed the most toxicity relief of all the treated groups. In the pharmacokinetic study, the dosing time dependency of toxicities was not related to the daily variation of pharmacokinetics of adriamycin and docetaxel. A significant 24-hour rhythm of G2-M phase distribution was found in myelocyte cells of nontreated mice. The daily variation of leukopenia caused by docetaxel corresponded to the 24-hour rhythm of G 2-M phase distribution. These findings reveal that the therapeutic index of the combined chemotherapy can be improved by administering adriamycin and docetaxel at the time when the most adverse effects are relieved in each drug.",
author = "Mayumi Tabuchi and Hideto To and Hiromi Sakaguchi and Naho Goto and Ayako Takeuchi and Shun Higuchi and Shigehiro Ohdo",
year = "2005",
month = "9",
day = "15",
doi = "10.1158/0008-5472.CAN-05-1161",
language = "English",
volume = "65",
pages = "8448--8454",
journal = "Cancer Research",
issn = "0008-5472",
number = "18",

}

TY - JOUR

T1 - Therapeutic index by combination of adriamycin and docetaxel depends on dosing time in mice

AU - Tabuchi, Mayumi

AU - To, Hideto

AU - Sakaguchi, Hiromi

AU - Goto, Naho

AU - Takeuchi, Ayako

AU - Higuchi, Shun

AU - Ohdo, Shigehiro

PY - 2005/9/15

Y1 - 2005/9/15

N2 - Although the combination of adriamycin and docetaxel showed a better cure rate against metastatic breast cancer, severe myelosuppression and cardiotoxicity were dose-limiting factors. The purpose of this study was to establish a suitable dosing schedule, based on a chronopharmacologic approach, to relieve severe adverse effects. In experiment 1, adriamycin or docetaxel was injected i.p. at 2, 6, 10, 14, 18, or 22 hours after light onset (HALO) to estimate toxicities. In experiment 2, the dosing time dependency of toxicity and pharmacokinetics were assessed in the combination of adriamycin and docetaxel. In addition, G2-M phase in myelocyte cells was determined in nontreated mice. Adverse effects caused by adriamycin were shown to be the worst at 2 HALO and the best at 14 HALO. On the other hand, docetaxel-induced adverse effects were more severe at 14 HALO than at 2 HALO. In the combination study, the D(2)-A(14) group, in which docetaxel was administered at 2 HALO followed by adriamycin at 14 HALO, showed the most toxicity relief of all the treated groups. In the pharmacokinetic study, the dosing time dependency of toxicities was not related to the daily variation of pharmacokinetics of adriamycin and docetaxel. A significant 24-hour rhythm of G2-M phase distribution was found in myelocyte cells of nontreated mice. The daily variation of leukopenia caused by docetaxel corresponded to the 24-hour rhythm of G 2-M phase distribution. These findings reveal that the therapeutic index of the combined chemotherapy can be improved by administering adriamycin and docetaxel at the time when the most adverse effects are relieved in each drug.

AB - Although the combination of adriamycin and docetaxel showed a better cure rate against metastatic breast cancer, severe myelosuppression and cardiotoxicity were dose-limiting factors. The purpose of this study was to establish a suitable dosing schedule, based on a chronopharmacologic approach, to relieve severe adverse effects. In experiment 1, adriamycin or docetaxel was injected i.p. at 2, 6, 10, 14, 18, or 22 hours after light onset (HALO) to estimate toxicities. In experiment 2, the dosing time dependency of toxicity and pharmacokinetics were assessed in the combination of adriamycin and docetaxel. In addition, G2-M phase in myelocyte cells was determined in nontreated mice. Adverse effects caused by adriamycin were shown to be the worst at 2 HALO and the best at 14 HALO. On the other hand, docetaxel-induced adverse effects were more severe at 14 HALO than at 2 HALO. In the combination study, the D(2)-A(14) group, in which docetaxel was administered at 2 HALO followed by adriamycin at 14 HALO, showed the most toxicity relief of all the treated groups. In the pharmacokinetic study, the dosing time dependency of toxicities was not related to the daily variation of pharmacokinetics of adriamycin and docetaxel. A significant 24-hour rhythm of G2-M phase distribution was found in myelocyte cells of nontreated mice. The daily variation of leukopenia caused by docetaxel corresponded to the 24-hour rhythm of G 2-M phase distribution. These findings reveal that the therapeutic index of the combined chemotherapy can be improved by administering adriamycin and docetaxel at the time when the most adverse effects are relieved in each drug.

UR - http://www.scopus.com/inward/record.url?scp=24944470170&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=24944470170&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-05-1161

DO - 10.1158/0008-5472.CAN-05-1161

M3 - Article

C2 - 16166324

AN - SCOPUS:24944470170

VL - 65

SP - 8448

EP - 8454

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 18

ER -