title: Paclitaxel plus ifosfamide in advanced ovarian cancer: a multicenter phase II study.
abstract: BACKGROUND
  While ovarian cancer is one of the most sensitive cancers to cytotoxic drugs, with objective response rates of 60-80% routinely being reported in previously untreated patients, the majority of individuals with advanced disease ultimately relapse. Paclitaxel, a new and novel antimicrotubule agent, has shown activity as a salvage therapy in epithelial ovarian cancer. More importantly, in a prior study, it has been shown to be active in tumors that have displayed resistance to platinum compounds, with a reported response rate of 20%. Ifosfamide has shown activity in the treatment of patients who previously demonstrated clinical resistance to a platinum-cyclophosphamide combination. Recently, a synergistic activity of Taxol combined with ifosfamide has been reported in ovarian cell lines. Based on these data, a phase I/II study of a combination treatment with paclitaxel and ifosfamide was performed.
  
  
  METHODS
  Thirty-one patients with recurrent ovarian cancer or ovarian cancer refractory to cisplatin (CDDP)-containing regimens were treated with paclitaxel at a dose of 135 mg/m2 on day 1; ifosfamide was administered at 1 g/m2 on days 2 and 3 for the first cycle and 1.5 and 2 g/m2 with the same schedule in cycles 2 and 3, respectively. In the absence of toxicity, the dose of ifosfamide was maintained at 2 g/m2 for the last three cycles. Cytotoxic therapy was repeated every 3 weeks.
  
  
  RESULTS
  A 30% overall objective response rate was achieved in the 30 patients assessable for response. Among 21 platinum-resistant patients, 4 partial responses (19%) were observed, while in the 9 platinum-sensitive patients 2 complete responses and 3 partial responses (55%) were observed. Myelosuppression was the predominant toxicity. Leukopenia (WHO grade 3-4) occurred in 10% of patients who received ifosfamide at a dose of 1 g/m2 and in 18% of patients treated with ifosfamide at 1.5 g/m2.
  
  
  CONCLUSIONS
  Our results confirmed a low activity of paclitaxel in platinum-resistant patients. The results of this combination treatment with paclitaxel-ifosfamide in our platinum-sensitive patients support further investigations in a randomized study of the combination regimen against paclitaxel alone or retreatment with organoplatinum compounds.
authors.affiliation: Servizio di Oncologia Medica II, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Miglietta
authors.forename: D
authors.initials: D
authors.lastname: Amoroso
authors.forename: M
authors.initials: M
authors.lastname: Bruzzone
authors.forename: C
authors.initials: C
authors.lastname: Granetto
authors.forename: E
authors.initials: E
authors.lastname: Catsafados
authors.forename: S
authors.initials: S
authors.lastname: Mammoliti
authors.forename: D
authors.initials: D
authors.lastname: Guarneri
authors.forename: F
authors.initials: F
authors.lastname: Pedulla
authors.forename: G
authors.initials: G
authors.lastname: Foglia
authors.forename: N
authors.initials: N
authors.lastname: Ragni
authors.forename: M C
authors.initials: MC
authors.lastname: Martini
authors.forename: F
authors.initials: F
authors.lastname: Brema
authors.forename: G
authors.initials: G
authors.lastname: Addamo
authors.forename: L
authors.initials: L
authors.lastname: Moraglio
authors.forename: G
authors.initials: G
authors.lastname: Pastorino
authors.forename: F
authors.initials: F
authors.lastname: Boccardo
mesh_terms: D000368:Aged; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D018906:Antineoplastic Agents, Alkylating; D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel; D007069:Ifosfamide