Cisplatin-Ifosfamide-gemcitabine as salvage chemotherapy in ovarian cancer patients pretreated with platinum compounds and Paclitaxel.
BACKGROUND
The role of combination chemotherapy regimens in the management of ovarian cancer patients with tumors previously exposed to platinum compounds and paclitaxel has not yet been defined. The present phase II study evaluated the activity and toxicity of a gemcitabine-ifosfamide-cisplatin combination in the aforementioned group of patients. Given the in vitro and in vivo synergism between the three agents, it was believed that using a three-drug combination would overcome tumor resistance to cisplatin.


METHODS
Twenty-four patients were enrolled in the study. The median age was 56 years and the median performance status 1. Eight (34%) had potentially platinum-sensitive, 6 (24%) had primary platinum-resistant and 10 (42%) patients had secondary platinum-resistant tumors. Treatment consisted of gemcitabine 1 g/m(2) i.v. on days 1 and 8, cisplatin 75 mg/m(2) i.v. over 2 h fractionated over days 8 and 9, and ifosfamide 5 mg/m(2) i.v. over 1 h fractionated on days 8-9 with mesna uroprotection. Courses were administered every 3 weeks on an outpatient basis. Granulocyte colony-stimulating factor (G-CSF) was given at a dose of 5 microg/kg/day on days 10-14. A median of 4 cycles were administered with the delivered dose intensity at 85% of the planned dose for the three agents.


RESULTS
Among 24 patients evaluable for response and toxicity, there were 8 partial responses with a response rate of 33% (95% confidence interval 16.4-55%). Stable disease was recorded in 6 (25.7) and progressive disease in 10 (42%) patients. Subgroup analysis revealed a response rate of 50% in potentially platinum-sensitive, 16.5% in primary platinum-resistant and 30% in secondary platinum-resistant tumors. The median response duration was 5 months (range 3-12 months), the median time to progression 6 months (range 3-16 months) and the median survival 12 months (range 3-24 months). Myelotoxicity was significant, with neutropenia grade 3 and 4 occurring in 35% and 20% of patients, respectively. Four episodes (3.5% of all cycles) of febrile neutropenia were documented and were well managed with oral antibiotics and G-CSF continuation until complete recovery. Grade 1, 2 and 3 peripheral neuropathy developed in 40%, 30%, and 10% of patients, respectively.


CONCLUSIONS
The three-drug combination demonstrated a significant effectiveness in potentially platinum-sensitive tumors and a moderate efficacy in platinum-resistant tumors. The regimen, although myelotoxic, is tolerable with G-CSF support. Further investigation via comparative studies is required to define any superiority of the present regimen over doublets of the three agents in this group of patients.
Polyzos
Aristides
A
Medical Oncology Unit,Laiko General Hospital, Athens University School of Medicine, Athens, Greece. panoraiap@med.uoa.gr
Tsavaris
Nikolas
N
Gogas
Helen
H
Lagadas
Antonios
A
Polyzos
Kostas
K
Giannakopoulos
Kostas
K
Felekouras
Evangelos
E
Tsigris
Christos
C
Karatzas
Theodoros
T
Papadopoulos
Othon
O
Giannopoulos
Athanasios
A
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D017239:Paclitaxel / Q000008:administration & dosage; D010349:Patient Compliance; D016879:Salvage Therapy; D000093542:Gemcitabine
D003841:Deoxycytidine; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide; D000093542:Gemcitabine