Abstract
Background: Multidrug resistance protein could be a target for improving the efficacy of paclitaxel (PXL). Toremifene (TOR) may moderate P-gp-related drug resistance in vitro. Some P-gp moderators may change the pharmacokinetic parameters of PXL in vivo. A pharmacokinetic (PK) study in metastatic breast cancer patients (MBC) was conducted to determine the safety and efficacy of PXL and TOR. Method and patients: Fifteen patients received 80 mg/m2 PXL (i.v.) weekly and 120 mg/body TOR (p.o.) daily. For the pharmacokinetic study, PXL was administered on days 1, 8, 15, 32, and 39; TOR was given from day 18 to the end of study. On days 1, 8, 15, 18, 32, and 39, blood samples were collected from the patients who received either PXL alone or PXL + TOR, and these were analyzed by high-performance liquid chromatography. Results: Among the 15 patients enrolled in the study, one showed a partial response, and eight had a stable disease. TOR caused no specific adverse events that were greater than grade 3, and its toxicity profile in combination with PXL was similar to that of PXL monotherapy. The PK profile of PXL was similar with or without TOR. The PK parameters of PXL indicated no inter- or intra-patient variability in previously treated patients with MBC. No increased PXL toxicity was observed. Conclusion: The PK profile of combined PXL and TOR was similar to that of PXL monotherapy. The addition of TOR to PXL in previously treated patients with MBC appears safe.
| Original language | English |
|---|---|
| Pages (from-to) | 113-120 |
| Number of pages | 8 |
| Journal | Breast Cancer |
| Volume | 16 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - 2009 |
Fingerprint
Keywords
- Antiestrogens
- Breast cancer
- Chemoendocrine therapy
- Drug resistance
- Paclitaxel
- Toremifene
ASJC Scopus subject areas
- Oncology
- Pharmacology (medical)
- Radiology Nuclear Medicine and imaging
Cite this
Pharmacokinetic analysis of a combined chemoendocrine treatment with paclitaxel and toremifene for metastatic breast cancer. / Saeki, Toshiaki; Okita, Atsushi; Aogi, Kenjiro; Kakishita, Tomokazu; Okita, Riki; Taira, Naruto; Ohama, Yumi; Takashima, Shigemitsu; Nishikawa, Kiyohiro.
In: Breast Cancer, Vol. 16, No. 2, 2009, p. 113-120.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pharmacokinetic analysis of a combined chemoendocrine treatment with paclitaxel and toremifene for metastatic breast cancer
AU - Saeki, Toshiaki
AU - Okita, Atsushi
AU - Aogi, Kenjiro
AU - Kakishita, Tomokazu
AU - Okita, Riki
AU - Taira, Naruto
AU - Ohama, Yumi
AU - Takashima, Shigemitsu
AU - Nishikawa, Kiyohiro
PY - 2009
Y1 - 2009
N2 - Background: Multidrug resistance protein could be a target for improving the efficacy of paclitaxel (PXL). Toremifene (TOR) may moderate P-gp-related drug resistance in vitro. Some P-gp moderators may change the pharmacokinetic parameters of PXL in vivo. A pharmacokinetic (PK) study in metastatic breast cancer patients (MBC) was conducted to determine the safety and efficacy of PXL and TOR. Method and patients: Fifteen patients received 80 mg/m2 PXL (i.v.) weekly and 120 mg/body TOR (p.o.) daily. For the pharmacokinetic study, PXL was administered on days 1, 8, 15, 32, and 39; TOR was given from day 18 to the end of study. On days 1, 8, 15, 18, 32, and 39, blood samples were collected from the patients who received either PXL alone or PXL + TOR, and these were analyzed by high-performance liquid chromatography. Results: Among the 15 patients enrolled in the study, one showed a partial response, and eight had a stable disease. TOR caused no specific adverse events that were greater than grade 3, and its toxicity profile in combination with PXL was similar to that of PXL monotherapy. The PK profile of PXL was similar with or without TOR. The PK parameters of PXL indicated no inter- or intra-patient variability in previously treated patients with MBC. No increased PXL toxicity was observed. Conclusion: The PK profile of combined PXL and TOR was similar to that of PXL monotherapy. The addition of TOR to PXL in previously treated patients with MBC appears safe.
AB - Background: Multidrug resistance protein could be a target for improving the efficacy of paclitaxel (PXL). Toremifene (TOR) may moderate P-gp-related drug resistance in vitro. Some P-gp moderators may change the pharmacokinetic parameters of PXL in vivo. A pharmacokinetic (PK) study in metastatic breast cancer patients (MBC) was conducted to determine the safety and efficacy of PXL and TOR. Method and patients: Fifteen patients received 80 mg/m2 PXL (i.v.) weekly and 120 mg/body TOR (p.o.) daily. For the pharmacokinetic study, PXL was administered on days 1, 8, 15, 32, and 39; TOR was given from day 18 to the end of study. On days 1, 8, 15, 18, 32, and 39, blood samples were collected from the patients who received either PXL alone or PXL + TOR, and these were analyzed by high-performance liquid chromatography. Results: Among the 15 patients enrolled in the study, one showed a partial response, and eight had a stable disease. TOR caused no specific adverse events that were greater than grade 3, and its toxicity profile in combination with PXL was similar to that of PXL monotherapy. The PK profile of PXL was similar with or without TOR. The PK parameters of PXL indicated no inter- or intra-patient variability in previously treated patients with MBC. No increased PXL toxicity was observed. Conclusion: The PK profile of combined PXL and TOR was similar to that of PXL monotherapy. The addition of TOR to PXL in previously treated patients with MBC appears safe.
KW - Antiestrogens
KW - Breast cancer
KW - Chemoendocrine therapy
KW - Drug resistance
KW - Paclitaxel
KW - Toremifene
UR - http://www.scopus.com/inward/record.url?scp=65249090187&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=65249090187&partnerID=8YFLogxK
U2 - 10.1007/s12282-008-0075-7
DO - 10.1007/s12282-008-0075-7
M3 - Article
C2 - 18936884
AN - SCOPUS:65249090187
VL - 16
SP - 113
EP - 120
JO - Breast Cancer
JF - Breast Cancer
SN - 1340-6868
IS - 2
ER -