title: Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer.
abstract: OBJECTIVE
  This multicenter phase II trial evaluated the efficacy and safety of weekly nanoparticle albumin-bound paclitaxel with carboplatin and weekly trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer (MBC).
  
  
  METHODS
  We treated 32 patients who had measurable MBC that was HER2-positive defined by an immunohistochemical staining score of 3+ or gene amplification by fluorescence in situ hybridization, required for those with an IHC of 2+. Patients were treated with albumin-bound paclitaxel 100 mg/m2 and carboplatin at area under the curve (AUC) = 2 on days 1, 8, and 15 of a 28-day cycle. Trastuzumab was administered at 2 mg/kg weekly after a loading dose of 4 mg/kg. Because of hypersensitivity reactions occurring during carboplatin infusion numbers 6-8 in 4 of the first 13 patients with this premedication-free regimen, the protocol was amended for carboplatin and dosed at AUC = 6 day 1 each 28-day cycle, in lieu of introducing steroid prophylaxis. Patients were treated with 6 cycles and allowed to continue with all 3 drugs or trastuzumab alone if free of progression and unacceptable toxicity after 6 cycles.
  
  
  RESULTS
  The overall response rate (ORR) was 62.5% (95% CI, 45.7%-79.3%) with 3 confirmed complete responders (CRs; 9%) and 17 confirmed partial responses (PRs; 53%). An additional 6 patients (19%) had stable disease (SD) for greater than 16 weeks for a clinical benefit rate (ORR + SD > 16 weeks) of 81%. As of April 16, 2009, 20 patients (63%) had progressed with a median progression-free survival (PFS) of 16.6 months (95% CI, 7.5-26.5 months). Antitumor activity was similar for patients treated with weekly carboplatin and every-4-week carboplatin (ORR, 65% vs. 67%, respectively). Hematologic toxicities were the only grade 4 toxicities noted and were infrequent with grade 4 neutropenia in 3 patients (9%) and 1 febrile neutropenia. Grade 2/3 peripheral neuropathy was uncommon (13%/3%).
  
  
  CONCLUSIONS
  Weekly albumin-bound paclitaxel with carboplatin and trastuzumab is highly active in HER2-overexpressing MBC. In the absence of corticosteroid premedication, which we avoided with albumin-bound paclitaxel, carboplatin seems best dosed every 4 weeks rather than weekly because of carboplatin-associated hypersensitivity reactions. The regimen was very well tolerated with few grade 3 and 4 nonhematologic toxicities experienced, and severe hematologic toxicity and peripheral neuropathy were infrequent.
authors: Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors: Alison K
authors: AK
authors: Conlin
authors: Andrew D
authors: AD
authors: Seidman
authors: Ariadne
authors: A
authors: Bach
authors: Diana
authors: D
authors: Lake
authors: Maura
authors: M
authors: Dickler
authors: Gabriella
authors: G
authors: D'Andrea
authors: Tiffany
authors: T
authors: Traina
authors: Michael
authors: M
authors: Danso
authors: Adam M
authors: AM
authors: Brufsky
authors: Mansoor
authors: M
authors: Saleh
authors: Alicia
authors: A
authors: Clawson
authors: Clifford A
authors: CA
authors: Hudis
mesh_terms: D000328:Adult; D000368:Aged; D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000008:administration & dosage / Q000009:adverse effects; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D018572:Disease-Free Survival; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D053758:Nanoparticles; D009362:Neoplasm Metastasis; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis / Q000235:genetics; D000068878:Trastuzumab
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab