title: Phase II trial of imatinib mesylate in patients with recurrent platinum- and taxane-resistant low-grade serous carcinoma of the ovary, peritoneum, or fallopian tube.
abstract: OBJECTIVE
  To evaluate the efficacy and tolerability of imatinib mesylate in patients with recurrent low-grade serous carcinoma (LGSC) of the ovary, peritoneum, or fallopian tube.
  
  
  METHODS
  This open-label, single-institution phase II trial enrolled patients with platinum-resistant LGSC who had measurable disease, had received up to 4 platinum- and/or taxane-containing chemotherapy regimens, and had been previously screened for at least one imatinib targeted biomarker (c-kit, platelet-derived growth factor receptor [PDGFR]-β, or bcr-abl). Imatinib (600 mg) was administered daily for one 6-week course and continued in the absence of toxicity and disease progression.
  
  
  RESULTS
  Thirteen patients were enrolled; 12 were evaluable for toxicity, and 11 were evaluable for response. A total of 17 courses were administered (median, 1 course; range, 1-5 courses). Complete or partial responses were not observed. One patient had stable disease for 7.3 months. c-Kit, bcr-abl, or PDGFR-β were present in 48%, 77%, and 100% of patients, respectively. No correlation between best response (stable disease) and the presence of imatinib-targeted biomarkers was observed. Adverse events included grade 3 skin rash in one patient leading to discontinuation of the drug, and grade 3 febrile neutropenia and grade 2 weight gain in two patients leading to dose reductions. The most common grade 1 or 2 toxicities were fatigue (66%), nausea/vomiting (66%), and diarrhea (41%); grade 3 toxicities included skin rash and granulocytopenia events. No grade 4 or 5 toxicities were observed. The median progression-free survival time was 1.3 months (95% CI, 1.27, 1.40 months), and the median overall survival time was 14.9 months (95% CI, 11.0, 18.9 months).
  
  
  CONCLUSIONS
  Imatinib is well-tolerated but has no activity in patients with platinum- and taxane-resistant LGSC or the ovary, peritoneum, or fallopian tube.
authors.affiliation: Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77230-1439, USA. nachete54@hotmail.com
authors.forename: Ignacio Romero
authors.initials: IR
authors.lastname: Noguera
authors.forename: Charlotte C
authors.initials: CC
authors.lastname: Sun
authors.forename: Russell R
authors.initials: RR
authors.lastname: Broaddus
authors.forename: Donna
authors.initials: D
authors.lastname: Branham
authors.forename: Charles F
authors.initials: CF
authors.lastname: Levenback
authors.forename: Pedro T
authors.initials: PT
authors.lastname: Ramirez
authors.forename: Anil K
authors.initials: AK
authors.lastname: Sood
authors.forename: Robert L
authors.initials: RL
authors.lastname: Coleman
authors.forename: David M
authors.initials: DM
authors.lastname: Gershenson
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D001549:Benzamides; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy*; D019008:Drug Resistance, Neoplasm; D005185:Fallopian Tube Neoplasms / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000068877:Imatinib Mesylate; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D010534:Peritoneal Neoplasms / Q000188:drug therapy*; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use; D011743:Pyrimidines / Q000009:adverse effects / Q000627:therapeutic use*; D043823:Taxoids / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D009944:Organoplatinum Compounds; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D043823:Taxoids; D000068877:Imatinib Mesylate