title: G3139 (Genasense) in patients with advanced merkel cell carcinoma.
abstract: OBJECTIVE
  Merkel cell carcinoma (MCC) is a rare, aggressive neuroendocrine malignancy of the skin. Preclinical studies have identified up-regulation of the critical antiapoptosis gene bcl-2 in MCC. We conducted a multicenter phase II trial of the novel bcl-2 antisense agent (G3139, Genasense) in patients with advanced MCC.
  
  
  METHODS
  Twelve patients (9 men, 3 women) with histologically confirmed metastatic or regionally recurrent MCC were enrolled. Ten patients (83%) had received prior chemotherapy. Eight patients (67%) had Karnofsky performance status of 90 to 100. Patients received continuous IV infusion of G3139 (7 mg/kg/d) via central venous access in an outpatient setting for 14 days, followed by a 7-day rest period. Response was assessed at 6-week intervals. Patients were allowed to continue therapy until unacceptable toxicity or disease progression.
  
  
  RESULTS
  No objective responses were observed. The best response was stable disease in 3 patients and progressive disease in 9 patients. A median of 4 doses per patient (total 46 doses) was administered. Dose delays and/or reductions were required in 6 patients. One patient developed grade 4 lymphopenia. One patient developed grade 3 renal failure characterized by grade 3-elevated creatinine and grade 4 hyperkalemia. Other grade 3 events included cytopenia (n = 5), aspartate aminotransferase/alanine aminotranferease elevation (n = 3), hypophosphatemia (n = 2), and pain (n = 1). The most frequent grade 1 to 2 toxicities were elevated creatinine, ALT elevation, hypokalemia, lymphopenia, and fatigue.
  
  
  CONCLUSIONS
  Bcl-2 antisense therapy (G3139) was well tolerated among patients with advanced MCC. Although probable antitumor activity was documented in 1 patient, no objective responses per Response Evaluation Criteria in Solid Tumors criteria were observed.
authors.affiliation: Division of Hematology and Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA. Manisha.Shah@osumc.edu
authors.forename: Manisha H
authors.initials: MH
authors.lastname: Shah
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Varker
authors.forename: Minden
authors.initials: M
authors.lastname: Collamore
authors.forename: James A
authors.initials: JA
authors.lastname: Zwiebel
authors.forename: Daniel
authors.initials: D
authors.lastname: Coit
authors.forename: David
authors.initials: D
authors.lastname: Kelsen
authors.forename: Ki Y
authors.initials: KY
authors.lastname: Chung
mesh_terms: D000368:Aged; D015266:Carcinoma, Merkel Cell / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D011379:Prognosis; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015996:Survival Rate; D013873:Thionucleotides / Q000627:therapeutic use*
chemical_list: D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; C408162:oblimersen