Phase II Study of Ifosfamide Plus Daily Oral Etoposide in Previously Treated Ovarian Cancer

Abstract

Advanced epithelial ovarian carcinoma is a chemosensitive tumor to platinum plus paclitaxel combination chemotherapy. However, most patients develop recurrences following their initial platinum-based regimen and are candidates for subsequent chemotherapy. Several chemotherapeutic drugs have been tested as single therapeutic agents or in combination for relapsed epithelial ovarian carcinoma. The response rate has been modest with no obvious advantage to combination chemotherapy versus single agents. Both oral etoposide and ifosfamide have shown activity as single agents in pretreated patients. We completed a phase II study at the Hoosier Oncology Group utilizing oral etoposide plus ifosfamide in patients with relapsed ovarian epithelial carcinoma. Fourteen patients entered the study. Ifosfamide was given intravenously (IV) at a dose of 1.2 g/m2/d on days 1 to 4 with mesna 300 mg/m2 IV 15 minutes prior to and 4 and 8 hours after ifosfamide infusion. Etoposide was administered as 37.5 mg/m2/d orally on days 1 to 14. This regimen was repeated every 28 days until disease progression or for a maximum of 6 cycles. Grade III to IV granulocytopenia occurred in 9 patients (64%), with 2 neutropenic infections, but with no therapy-related deaths. Grade III to IV thrombocytopenia occurred in 3 patients (21%), and grade III to IV nausea and vomiting in 1 patient. No renal, pulmonary, hepatic, cardiac, or serious neurotoxicity was observed. Two patients (14%) achieved partial response, and additional 5 (35%) patients had stable disease. The 1-year survival probability using Kaplan-Meier analysis was 0.8. In this small sample-size trial, we did not demonstrate an advantage to this combination regimen compared to these or other single agents.

Phase II Study of Combination Chemotherapy with Etoposide and Ifosfamide in Patients with Heavily Pretreated Recurrent or Persistent Epithelial Ovarian Cancer

“…All of the trials used ETI as second- or third line of chemotherapy. Three of these phase II trials used IV etoposide (19-21), while the other two used oral etoposide (22, 23). Bruzzone et al (20) study resulted in no responses in 12 patients progressing or relapsing after primary cisplatin-containing combination, Trope et al (21) obtained the following results; in 29 patients who received cisplatin as first-line and were deemed to be platinum-resistant, used ETI regimen same dose to ours, RR was 21%, the median time to disease progression was 6 months.…”

Retrospective Study of Combination Chemotherapy With Etoposide and Ifosfamide in Patients With Heavily Pretreated Recurrent or Persistent Epithelial Ovarian Cancer

“…In this condition, we can expect 34.5% RR and 9.2 months of median survival. Several reports including ours have been published on ETI regimen in recurrent EOC [13,[23][24][25][26]. It has been reviewed by Kang et al [14] Most of them used IV etoposide and ifosfmaide, but 2 investigators used oral etoposide and IV ifosfamide.…”

Retrospective study of combination chemotherapy with etoposide and ifosfamide in patients with heavily pretreated recurrent or persistent epithelial ovarian cancer

“…Several reports including ours have been published on ETI regimen in recurrent EOC [ 13 23 24 25 26 ]. It has been reviewed by Kang et al [ 14 ] Most of them used IV etoposide and ifosfmaide, but 2 investigators used oral etoposide and IV ifosfamide.…”