title: Efficacy and tolerability of weekly paclitaxel in combination with high-dose toremifene citrate in patients with metastatic breast cancer.
abstract: Toremifene citrate is expected to prevent drug resistance in cancer patients by inhibiting p-glycoprotein activity. The safety and efficacy of combination therapy with high-dose toremifene citrate and paclitaxel were investigated. Between December 2003 and June 2004, 15 women with a mean age of 53 years old with metastatic breast cancer were enrolled. The administration schedule was 80 mg/m2 of paclitaxel given on Days 1, 8, and 15, and 120 mg/day of toremifene citrate orally administered starting on Day 18. On Days 32 and 39, paclitaxel was concurrently administered again. Toxicities, response rate, and time to treatment failure were assessed. All patients had been treated with endocrine or chemotherapy. Grade 3 leukopenia occurred in 2 patients on the administration of paclitaxel alone, and grade 3 febrile neutropenia occurred in 1 patient given the combination therapy. There was no grade 3 or greater non-hematological toxicity. There was no complete response and 1 partial response, producing a response rate of 6.7%. Median time to treatment failure was 2.7 months. Combination therapy of paclitaxel and toremifene was safe and well tolerated with minimal toxicity. Further clinical trials targeting patients with functional p-glycoprotein are warranted.
authors.affiliation: Department of Surgery, National Hospital Organization, Shikoku Cancer Center, Matsuyama 791-0280, Japan. HZI06166@nifty.ne.jp
authors.forename: Atsushi
authors.initials: A
authors.lastname: Okita
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Saeki
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Aogi
authors.forename: Shozo
authors.initials: S
authors.lastname: Osumi
authors.forename: Shigemitsu
authors.initials: S
authors.lastname: Takashima
authors.forename: Riki
authors.initials: R
authors.lastname: Okita
authors.forename: Naruto
authors.initials: N
authors.lastname: Taira
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Kakishita
authors.forename: Akira
authors.initials: A
authors.lastname: Kurita
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D017312:Toremifene / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D017312:Toremifene; D017239:Paclitaxel