Chin Med J (Engl). 2012 Mar;125(5):775-9.
Oral etoposide monotherapy is effective for metastatic breast cancer with heavy prior therapy.
Yuan P,
Xu BH,
Wang JY,
Ma F,
Fan Y,
Li Q,
Zhang P.
FREE TEXT
Source
Department of Medical Oncology, Cancer Hospital (Institute), Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100021, China.
Abstract
BACKGROUND:
Treatment option for metastatic breast cancer (MBC) patients pre-treated with chemotherapy is limited. Oral etoposide has shown some promises in these patients. However,
patients who received heavy prior chemotherapy may have poor tolerance to prolonged oral etoposide exposure. This study is a single-arm clinical trial that evaluates the efficacy and safety of short-term oral etoposide in Chinese patients with MBC who had received heavy prior therapy.
METHODS:
MBC patients receiving at least two chemotherapy regimens prior to the enrollment were treated with repeated cycles of
oral etoposide (60 mg×m(-2)×d(-1) on days 1 - 10, followed by 11 days of rest). The primary end point was the progression free survival (PFS). The secondary end points were objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and toxicity profiles.
RESULTS:
Thirty-two patients received 230 cycles of oral etoposide with a median of 6 cycles (range, 2 - 20 cycles) per patient. Eight patients (25%) had partial response (PR) and 14 patients achieved stable disease (SD). The
ORR was 25%. Nine patients achieved SD for more than 24 weeks and CBR was 53%. The median PFS and OS were 5 (range, 1.5 - 17.0 months) and 16 months (range, 3.0 - 51.0 months), respectively. The patients who achieved clinical benefit had longer survival time than those who did not (25.0 versus 11.0 months, P < 0.01). Among the 16 patients who received more than four regimens prior to this study, four patients achieved PR and four achieved SD for more than 24 weeks, with a CBR of 50%. The most common hematologic adverse events were anemia (43.8%) and neutropenia (38.5%). Nausea/vomiting (75.0%) and alopecia (62.5%) were the most frequent non-hematologic toxicities.
CONCLUSION:
Oral etoposide is effective and well tolerated in Chinese women with heavily pretreated MBC.
- PMID:
- 22490573
- [PubMed - in process]
Breast Cancer. 2010 Nov 19. [Epub ahead of print]
Etoposide, mitomycin, and methotrexate combination in heavily treated breast cancer: a retrospective study.
Aldabbagh K,
Pouderoux S,
Roca L,
Poujol S,
Fabbro M,
Romieu G,
Jacot W.
Department of Medical Oncology, CRLC Val d'Aurelle, 208 rue des Apothicaires, 34298, Montpellier Cedex 5, France,
Kais.Aldabbagh@valdorel.fnclcc.fr.
LINK
Abstract
BACKGROUND: Since 2004, metastatic breast cancer patients pretreated with anthracyclines, taxanes, and capecitabine have been treated in our institution with a combination of mitomycin C, methotrexate, and VP-16 (VMM). We report in this study a retrospective analysis of the activity and safety of the VMM combination.
METHODS: Patients were treated with a combination of VP-16 (100 mg/m(2) on day 1), mitomycin C (MMC, 10 mg/m(2) on day 1), and methotrexate (MTX, 12.5 mg/m(2) twice a day on day 2 and 3) in a 21-day cycle.
RESULTS: Seventy-five patients were treated. Median age was 48 years. A total of 256 cycles were administered. Median relative dose intensities were 0.87, 0.87, and 0.95 for VP-16, MMC, and MTX, respectively.
Objective response rate was 31%, with a clinical benefit rate of 47%. Median response duration was 5.8 months. Median disease stabilization duration was 9.1 months. Median progression-free survival (PFS) was 4.2 months with a 14% 1-year PFS rate. Median overall survival (OS) was 6.2 months, with a 25% 1-year OS rate. Myelosuppression was the most common toxicity. The most commonly reported extra-hematological adverse event (AE) was fatigue. Emesis and alopecia were rarely reported.
CONCLUSIONS:
This combination appears to be effective and well tolerated in this heavily pretreated metastatic breast cancer population.
PMID: 21088942 [PubMed - as supplied by publisher]
Biomed Pharmacother. 2012 Feb;66(1):29-35. Epub 2011 Dec 28.
Expression analysis of TOP2A, MSH2 and MLH1 genes in MCF7 cells at different levels of etoposide resistance.
Kaplan E,
Gündüz U.
Source
Middle East Technical University, Department of Biological Sciences, 06531, Ankara, Turkey.
LINK
Abstract
PURPOSE:
Development of resistance against anti-cancer drugs is one of the major obstacles of chemotherapy in the treatment of cancer.
Etoposide is a topoisomerase II alpha (TOP2A) inhibitor, which is used in the treatment of breast cancer. Alterations in the expression of drug targets or DNA repair genes are among the important resistance mechanisms against TOP2A inhibitors. In this study, expression changes in TOP2A gene and two important mismatch repair (MMR) genes MSH2 and MLH1 were examined in order to understand the relationship between differential expression of these genes and drug resistance against etoposide.
METHODS:
Resistant cell lines were developed from parental MCF7 cell line by stepwise selection in increasing doses of etoposide. Total RNA was isolated from parental and resistant cell lines by using TriReagent. Expression levels of TOP2A, MSH2 and MLH1 were analysed by reverse transcription quantitative polymerase chain reaction (RT-qPCR). Statistical analyses were performed by one way ANOVA.
RESULTS:
Etoposide resistant sublines MCF7/1000E, MCF7/1250E and MCF7/2000E were approximately 2, 3 and 4 fold resistant relative to parental MCF7/S cells, respectively. TOP2A, MSH2 and MLH1 expressions decreased in etoposide resistant sublines relative to MCF7/S cells. Expression levels of TOP2A and MLH1 in resistant sublines differed between 10-95 and 18-58 percent of the expression levels in the parental cells, respectively. MSH2 expression levels were decreased 18-82 percent in resistant cells. A transient 15 percent increase in the expression of this gene was observed in subline MCF7/1250E.
CONCLUSIONS:
Decrease in the expression levels of TOP2A, MSH2 and MLH1 may play significant roles in the development of chemotherapeutic resistance to etoposide in breast cancer. These genes may be considered for further development of new strategies to overcome resistance against topoisomerase II inhibitors.
© 2011 Elsevier Masson SAS. All rights reserved.
- PMID:
- 22285073
- [PubMed - in process]
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