TITLE:
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
AUTHORS:
Mieko Yanagisawa, Keigo Yorozu, Mitsue Kurasawa, Yoichiro Moriya, Naoki Harada
KEYWORDS:
Triple Negative Breast Cancer; Capecitabine; Cyclophosphamide; Bevacizumab; Paclitaxel; Xenograft Model
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.4 No.7,
September
4,
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 + CPA was significantly stronger than
that of CPA or CAPE alone (p + 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.