title: Efficacy of meloxicam in combination with preoperative chemotherapy for breast cancer - Japan Breast Cancer Research Network (JBCRN) 02-1 trial.
abstract: BACKGROUND
  We reported that doxorubicin and cyclophosphamide (DC) followed by weekly paclitaxel is an active and manageable preoperative regimen for breast cancer patients. However, as one of the side effects of paclitaxel, neuropathy was noted in up to 30% of patients. Cyclooxygenase-2 (COX-2) and its derived prostaglandins play a role in stimulating angiogenesis, inhibiting apoptosis, and suppressing the immune response. Some recent studies showed that COX-2 inhibitors, such as meloxicam, have the potential to enhance tumor suppression and reduce the severity of paclitaxel-induced neuropathy.
  
  
  METHODS
  Four cycles of DC (doxorubicin: 60 mg/m(2) and cyclophosphamide: 600 mg/m(2)) administered intravenously (i.v.) on day 1 every 21 days were followed by 12 cycles of paclitaxel i.v. (80 mg/m(2)) every 7 days, prior to surgery. During paclitaxel therapy, breast cancer patients were administered meloxicam (10 mg per day) daily, when experiencing symptoms of grade 2 neuropathy (motor or sensory). The primary endpoint was the pCR rate achieved with the treatment.
  
  
  RESULTS
  Forty-three patients received preoperative chemotherapy between April 2004 and March 2007 at six centers. The patient population was identified from a database of the Japan Breast Cancer Research Network. Clinical responses were rated as clinically complete response (cCR) in 9 patients (22%), clinically partial response (cPR) in 25 patients (59%), and clinically stable disease (cSD) in 9 patients (19%). pCR was seen in 25.6%. In addition, we identified 15 patients, who developed grade 2 neuropathy during paclitaxel therapy and subsequently received meloxicam. Meloxicam application had a marked effect within 28 days of initiation. The sensory neuropathy of the patients was reduced gradually, but their motor neuropathy did not improve. Five out of the 15 patients with neuropathy experienced symptom improvement after meloxicam treatment (p<0.05; before versus after 2 months of meloxicam administration). Furthermore, among the 15 patients, who received meloxicam, clinical responses were rated as cCR in 2 patients, cPR in 4 patients, and cSD in 9 patients. The pCR was seen in 4 patients (26.7%).
  
  
  CONCLUSIONS
  Although meloxicam in combination with DC and weekly paclitaxel chemotherapy did not show promising therapeutic activity, it may provide some relief for neuropathy.
authors.affiliation: Department of Surgery, Kansai Medical University, Hirakata, Osaka 570-8507, Japan. yamamotd@hirakata.ac.jp
authors.forename: Daigo
authors.initials: D
authors.lastname: Yamamoto
authors.forename: Satoru
authors.initials: S
authors.lastname: Iwase
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshida
authors.forename: Yujiro
authors.initials: Y
authors.lastname: Kuroda
authors.forename: Chizuko
authors.initials: C
authors.lastname: Yamamoto
authors.forename: Kaoru
authors.initials: K
authors.lastname: Kitamura
authors.forename: Hiroki
authors.initials: H
authors.lastname: Odagiri
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Nagumo
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000601:surgery*; D003131:Combined Modality Therapy; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007564:Japan; D016015:Logistic Models; D000077239:Meloxicam; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy; D011300:Preoperative Care; D013843:Thiazines / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D013843:Thiazines; D013844:Thiazoles; D000077239:Meloxicam