title: Phase 2 trial of paclitaxel, 13-cis retinoic acid, and interferon alfa-2b in the treatment of advanced stage or recurrent cervical cancer.
abstract: OBJECTIVE
  Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that down-regulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase 2 trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer.
  
  
  METHODS
  Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid, 1 mg/kg, and subcutaneous interferon alfa-2b, 6 mU/m, days 1 to 4, and intravenous paclitaxel, 175 mg/m, day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate.
  
  
  RESULTS
  Thirty-three patients were enrolled between March 2001 and June 2009. Thirty-one patients were eligible for evaluation of treatment response. Twenty-seven patients (82%) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30% (6 complete responses and 4 partial responses). Furthermore, 7 patients (21%) had stable disease. Grade 3 or 4 adverse events included neutropenia (n =16 [48%]), febrile neutropenia (n = 1 [3%]), and anemia (n = 1 [3%]). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95% confidence interval, 2.0-7.4 months), and overall survival was 11.2 months (95% confidence interval, 7.5-26.2 months). Of 6 patients with complete responses, 5 patients survived more than 2 years.
  
  
  CONCLUSIONS
  Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer.
authors.affiliation: *Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers-Robert Wood Johnson Medical School, New Brunswick, NJ; †Rutgers Cancer Institute of New Jersey, New Brunswick, NJ; ‡Rutgers New Jersey Medical School, Newark, NJ; and §John Theurer Cancer Center, Hackensack, NJ.
authors.forename: Mihae
authors.initials: M
authors.lastname: Song
authors.forename: Robert S
authors.initials: RS
authors.lastname: DiPaola
authors.forename: Bernadette M
authors.initials: BM
authors.lastname: Cracchiolo
authors.forename: Darlene G
authors.initials: DG
authors.lastname: Gibbon
authors.forename: Mira
authors.initials: M
authors.lastname: Hellmann
authors.forename: Wilberto
authors.initials: W
authors.lastname: Nieves-Neira
authors.forename: Ami
authors.initials: A
authors.lastname: Vaidya
authors.forename: Allison R
authors.initials: AR
authors.lastname: Wagreich
authors.forename: Weichung J
authors.initials: WJ
authors.lastname: Shih
authors.forename: Lorna
authors.initials: L
authors.lastname: Rodriguez-Rodriguez
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D000998:Antiviral Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D003879:Dermatologic Agents / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D015474:Isotretinoin / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D017239:Paclitaxel / Q000627:therapeutic use*; D011379:Prognosis; D011994:Recombinant Proteins / Q000627:therapeutic use; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D000998:Antiviral Agents; D003879:Dermatologic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D015474:Isotretinoin; D017239:Paclitaxel