title: Erlotinib added to carboplatin and paclitaxel as first-line treatment of ovarian cancer: a phase II study based on surgical reassessment.
abstract: BACKGROUND
  The purpose of this study was to determine whether adding the anti-epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to carboplatin/paclitaxel improved pathologic complete response (pCR) at reassessment surgery in epithelial ovarian, fallopian tube, or primary peritoneal cancers (OFPC).
  
  
  METHODS
  Patients with stage III-IV OFPC initiated treatment within 12 weeks of initial cytoreductive surgery or, after histologic confirmation of diagnosis, neoadjuvantly. Treatment included paclitaxel (175 mg/m²) and carboplatin (AUC 6) every 3 weeks for up to 6 cycles, plus oral erlotinib 150 mg daily. The primary objective was to determine whether the pCR rate at reassessment surgery was at least 60% after optimal cytoreduction at initial surgery (< 1cm residual disease), or at least 40% after suboptimal cytoreduction (at least 1cm residual disease) using a two-stage design (alpha=0.10, beta=0.10).
  
  
  RESULTS
  The study population included 56 patients with stage III-IV OFPC. EGFR gene amplification was present in 15% of the 20 tumors evaluated. Twenty-eight patients had protocol therapy after optimal cytoreduction (stratum I), 23 had protocol therapy either after suboptimal cytoreduction (stratum II), and 5 received neoadjuvant therapy prior to cytoreduction (stratum III). Pathologic CR was confirmed in 8 patients (29%; 95% confidence intervals 13%, 49%) in stratum I and 3 patients (11%, 95% C.I. 2%, 28%) in stratum II, which did not meet the prespecified efficacy endpoint in either stratum.
  
  
  CONCLUSIONS
  Among unselected patients, erlotinib plus carboplatin-paclitaxel did not improve pCR rates compared with historical experience with carboplatin-paclitaxel alone in patients with stage III-IV OFPC.
authors.affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, New York University School of Medicine, New York, NY, USA.
authors.forename: Stephanie V
authors.initials: SV
authors.lastname: Blank
authors.forename: Paul
authors.initials: P
authors.lastname: Christos
authors.forename: John P
authors.initials: JP
authors.lastname: Curtin
authors.forename: Noah
authors.initials: N
authors.lastname: Goldman
authors.forename: Carolyn D
authors.initials: CD
authors.lastname: Runowicz
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Sparano
authors.forename: Leonard
authors.initials: L
authors.lastname: Liebes
authors.forename: Helen X
authors.initials: HX
authors.lastname: Chen
authors.forename: Franco M
authors.initials: FM
authors.lastname: Muggia
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics; D000069347:Erlotinib Hydrochloride; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000601:surgery; D005260:Female; D005784:Gene Amplification / Q000187:drug effects; D018773:Genes, erbB-1 / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery*; D017239:Paclitaxel / Q000008:administration & dosage / Q000009:adverse effects; D010534:Peritoneal Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology / Q000601:surgery; D011799:Quinazolines / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D011799:Quinazolines; D016190:Carboplatin; D000069347:Erlotinib Hydrochloride; D066246:ErbB Receptors; D017239:Paclitaxel