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Combination Therapy of Capecitabine with Cyclophosphamide as a Second-Line Treatment after Failure of Paclitaxel plus Bevacizumab Treatment in a Human Triple Negative Breast Cancer Xenograft Model
- Source :
- Journal of Cancer Therapy. :1236-1241
- Publication Year :
- 2013
- Publisher :
- Scientific Research Publishing, Inc., 2013.
-
Abstract
- We examined the antitumor efficacy of the capecitabine (CAPE) plus cyclophosphamide (CPA) combination as a 2nd-line therapy after paclitaxel (PTX) plus bevacizumab (BEV) treatment in a xenograft model of human triple negative breast cancer (TNBC) cell line, MX-1. After tumor growth was confirmed, PTX (20 mg/kg; i.v.) + BEV (5 mg/kg; i.p.) treatment was started (Day 1). Each agent was administered once a week for 5 weeks and tumor regression was observed for at least the first 3 weeks. For 2nd-line treatment, we selected mice in which the tumor volume had increased from day 29 to day 36 and was within 130 - 250 mm3 on day 36. After randomization of mice selected on day 36, CPA (10 mg/kg; p.o.) and CAPE (539 mg/kg; p.o.) were administered daily for 14 days (days 36 - 49), followed by cessation of the drugs for 1 week. The tumor growth on day 57 was significantly suppressed in the CPA, CAPE and CAPE + CPA groups as compared with the control group (p < 0.05). Furthermore, the antitumor activity on day 57 of CAPE + CPA was significantly stronger than that of CPA or CAPE alone (p < 0.05). The thymidine phosphorylase (TP) level in tumor tissue was evaluated by immunohistochemistry on day 50, and was significantly higher in the CPA group than those in the control group (p < 0.05). Upregulation of TP in tumor tissues by CPA treatment would increase the 5-FU level in tumor tissues treated with CAPE. This would explain the possible mechanism that made CAPE + CPA superior to CAPE alone in the 2nd-line treatment. Our preclinical results suggest that the CAPE + CPA combination therapy may be effective as 2nd-line therapy after disease progression in PTX + BEV 1st-line treatment for TNBC patients.
- Subjects :
- Oncology
medicine.medical_specialty
Randomization
Combination therapy
Cyclophosphamide
Bevacizumab
business.industry
Pharmacology
Capecitabine
chemistry.chemical_compound
Paclitaxel
chemistry
Internal medicine
cardiovascular system
medicine
heterocyclic compounds
Thymidine phosphorylase
business
Triple-negative breast cancer
medicine.drug
Subjects
Details
- ISSN :
- 21511942 and 21511934
- Database :
- OpenAIRE
- Journal :
- Journal of Cancer Therapy
- Accession number :
- edsair.doi...........5b658aacb7a4d823a8a17fc89d7c35cb
- Full Text :
- https://doi.org/10.4236/jct.2013.47144