a "gentle" maintenance therapy for metastatic her2 bc with 46% clinical benefit rate!

[Lani]

This is hot off the press, but I have been following these studies out of Canada, Italy/Switzerland.

I previously brought this up when Tom thought (erroneously, Thank God, that his mother had recurred. Many rhematoid arthritis patients stay on low dose methotrexate for years without ill-effects. The doses are tiny compared to doses used in regular chemotherapy. The goal is not to kill quickly dividing cells, but rather to hit the "Achilles heel" of well-vascularized cancers, especially her2+ breast cancer, the lining cells of the new blood vessels the cancer "commands" to be formed to feed it. These cells are very sensitive to very low doses of these agents.

This is similar to my post today on curcumins. Often drugs/chemicals/biologic compounds have different effects depending what concentration is used.

1: BMC Cancer. 2006 Sep 15;6(1):225 [Epub ahead of print] Links
Trastuzumab in combination with metronomic cyclophosphamide and methotrexate in patients with Her-2 positive metastatic breast cancer.

Orlando L,
Cardillo A,
Ghisini R,
Rocca A,
Balduzzi A,
Torrisi R,
Peruzzotti G,
Goldhirsch A,
Pietri E,
Colleoni M.
ABSTRACT: BACKGROUND: HER2/neu overexpression is linked to promotion of angiogenesis in breast cancer. We therefore tested the activity of the combination of Trastuzumab with metronomic, low dose chemotherapy with cyclophosphamide (CTX) and methotrexate (MTX) in metastatic breast cancer (MBC). METHODS: Between April 2002 and June 2005, twenty-two patients with metastatic breast cancer with the presence of overexpression or amplification of HER2-/neu, all pre-treated with trastuzumab plus other cytotoxics, were treated with trastuzumab (6mg/kg every three weeks) in combination with metronomic chemotherapy (MTX 2.5 mg, bid on Day 1 and Day 4 every week) and CTX (50 mg daily) (CM). RESULTS: The 22 enrolled patients are evaluable: most had an ECOG performance status of 0 (17 pts), and all were pre-treated with chemotherapy for metastatic disease; 14 had progressive disease at study entry, and 11 had progressive disease during the last trastuzumab therapy. Metastatic sites included: lung (5 pts), liver (14 pts), bone (12 pts), lymph nodes (8 pts), central nervous system (CNS) (9 pts). We observed 4 partial remission (PR) (18%, 95% CI 5-40%), 10 stable disease (SD) (46%, 95% CI 24-68%), and 8 PD (36%, CI 17-59%). The clinical benefit (RP plus RC plus SD for ? 24 weeks) in all pts and in pts with disease resistant to previous trastuzumab therapy were 46% (95% CI, 24-68%) and 27% (95% CI, 6-61%), respectively. Median time to progression was 6 months and median duration of treatment was 5 months (range, 0,7 to 18.4 months and range, 1 to 18 months, respectively). Overall clinical toxicity was generally mild. Grade >2 reversible liver toxicity and leukopenia were reported in 5 and 3 pts, respectively. CONCLUSIONS: The combination of trastuzumab and metronomic chemotherapy is effective and minimally toxic in advanced breast cancer patients. The efficacy observed in patients with disease resistant to trastuzumab supports the need of larger trial to confirm a role of this combination to delay acquired trastuzumab resistance.
PMID: 16978400 [PubMed - as supplied by publisher]

[RhondaH]

as my mother went to get her Methotrexate today...I wonder if her doc would give her a little extra for me Moms had rheumatoid arthritis for over 20 years and has been on this MOST of this time.

Rhonda

[SusanV]

My dad also has been receiving infusions of methotrexate for his rhematoid athritis for several years. In fact I get my chemo one floor below him in the same hospital !