title: Phase II study of Pseudomonas aeruginosa-Mannose-Sensitive hemagglutinin in combination with capecitabine for Her-2-negative metastatic breast cancer pretreated with anthracycline and taxane.
abstract: OBJECTIVE
  Metastatic breast cancer (MBC) remains an incurable disease despite major therapeutic advances. Pseudomonas aeruginosa-mannose-sensitive hemagglutinin (PA-MSHA) has been established to have anti-proliferative effects against breast cancer cells in preclinical experiments, and is indicated for treatment of cancer in China. We performed a phase II trial combining PA-MSHA with capecitabine in patients with heavily pretreated MBC.
  
  
  METHODS
  Eligibility criteria included human epidermal growth factor receptor 2-negative MBC, prior therapy with anthracyclines and taxanes, at least one prior chemotherapy regimen for metastatic disease or early relapse after a taxane plus anthracycline adjuvant regimen, and adequate organ function and performance status. PA-MSHA 1 mg was administered subcutaneously every other day and capecitabine 1000 mg/m2 orally twice a day for 2 weeks on, 1 week off. The primary end point was progression-free survival.
  
  
  RESULTS
  A total of 97 patients were enrolled. Median progression-free survival (PFS) was 4.0 months [95 % confidence interval (CI) 3.0-4.9], which was not significantly different from that in historical controls. However, median PFS was significantly longer (8.2 months; 95 % CI 6.7-9.7) in 24 patients with moderate immune-related adverse events (irAEs) such as fever or skin induration at the injection site than in those with no or mild irAEs (3.1 months, 95 % CI 2.5-3.6; p = 0.003). Overall survival was also improved in these patients (25.4 vs. 16.4 months; p = 0.044). PA-MSHA has a good safety profile, with only 6 patients (6.2 %) discontinuing treatment. PA-MSHA did not increase capecitabine-related toxicities such as hand-foot syndrome, nausea, and vomiting.
  
  
  CONCLUSIONS
  Adding PA-MSHA to capecitabine has a good safety profile in patients with heavily pre-treated MBC, although benefit from this regimen might occur only in patients with moderate PA-MSHA-related adverse events.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01380808.
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Lv
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Cao
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhebin
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhonghua
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Leiping
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Breast Surgery, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Shao
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Biyun
authors.initials: B
authors.lastname: Wang
authors.affiliation: Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
authors.forename: Xichun
authors.initials: X
authors.lastname: Hu
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D000069287:Capecitabine / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D006388:Hemagglutinins / Q000276:immunology*; D006801:Humans; D008358:Mannose / Q000494:pharmacology*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009362:Neoplasm Metastasis; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000172:deficiency*; D012449:Safety; D016879:Salvage Therapy; D043823:Taxoids / Q000494:pharmacology; D055815:Young Adult
chemical_list: D018943:Anthracyclines; D000970:Antineoplastic Agents; D001952:Bridged-Ring Compounds; D000069287:Capecitabine; D006388:Hemagglutinins; D008358:Mannose; D018719:Erb-b2 Receptor Tyrosine Kinases; D043823:Taxoids; C080625:taxane; C508053:ERBB2 protein, human