Paclitaxel plus Ifosfamide in Advanced Ovarian Cancer

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. Patients and 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. Conclusion: 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.

Effect of culture conditions on the chemosensitivity of ovarian cancer cell lines

“…Long-term survival of patients with stage III or IV ovarian cancer is currently unusual and there is a need to develop better drugs for this disease [24][25][26]. Most of the agents available, and those tested here, are most effective against dividing cells.…”

Combination chemotherapy with paclitaxel and ifosfamide as the third-line regimen in patients with heavily pretreated small cell lung cancer

“…Paclitaxel has also yielded significant single-agent activity in relapsed SCLC patients, with an observed RR of 29% [20]. The incorporation of ifosfamide into combination chemotherapy with paclitaxel demonstrated enhanced activity and possibly synergistic effects in vitro [21], and has also shown significant activity in various types of malignancies [22][23][24]. However, the efficacy of the combination chemotherapy of paclitaxel and ifosfamide in relapsed or resistant SCLC as a salvage regimen remains to be evaluated.…”

Paclitaxel by 72-Hour Continuous Infusion Followed by Bolus Intravenous Ifosfamide or Epirubicin: Results of Two Phase I Studies

“…Consequently, and on the basis of the results of previous studies with paclitaxel administered through 3- or 24-hour infusion followed by ifosfamide or doxorubicin in patients with relapsed ovarian and breast cancer [2, 3, 4], we decided to select 72-hour continuous paclitaxel infusion followed by either ifosfamide or epirubicin for two consecutive phase I studies.…”

“…The obvious next step was the combination of paclitaxel with drugs with known activity in these diseases like anthracyclines and ifosfamide. Most of the clinical trials were conducted with paclitaxel administered through a 3- or 24-hour infusion in combination with either anthracyclines or ifosfamide [2, 3, 4]. Schedule and sequence-dependent toxicities as well as pharmacokinetic and/or pharmacodynamic interferences complicate the combination of paclitaxel with these agents [5].…”