PHASE-II TRIAL OF PACLITAXEL AND IFOSFAMIDE AS A SALVAGE TREATMENT INMETASTATIC BREAST-CANCER

Purpose. Treatment results in patients failing first-line chemotherapy in metastatic breast cancer (MBC) are still unsatisfactory, with pati ents exhibiting poor responses to salvage therapy and a short overall survival. Both paclitaxel and ifosfamide are able to produce objective tumor responses in this disease. Therefore, the antitumor effects and toxicity of their combined use could be worthwhile studying in patien ts progressing after doxorubicin-containing combinations. Patients and methods. This Phase II trial of paclitaxel/ifosfamide included patien ts with bi-dimensionally measurable metastatic breast cancer in second or third relapse, following anthracycline-containing regimens; ECOG P S < 2, and adequate hepatic, cardiac, renal, and hematological functio ns. Paclitaxel 175 mg/m2 was given on day 1, in a 3-hour infusion with appropriate antiallergic pre-medication; while ifosfamide 1.8 g/m2 wa s given on days 2, 3, 4 with mesna 360 mg/m2 i.v., 15 minutes before a nd 4 hours after ifosfamide administration, and 720 mg/m2 P.O.8 hours later at home, also on days 2, 3, 4. The cycles were repeated every 21 days, on an outpatient basis. Results. Twenty-four patients were accr ued for the study and 23 were considered eligible for the evaluation o f toxicity and response. Previous chemotherapy included: CMF/FAC (16 c ases); CMF plus mitoxantrone/FAC/cisplatin, vinblastine, mitomycin C ( 2 cases); and FAC/mitomycin C, vinblastine, and etoposide (5 cases). T here were 11 (48 %) objective responses (95% C.I.:27-69%), including 2 (9%) CR and 9 (39%) PR (95% C.I.: 0-21% and 19-61%, respectively). Fi ve (22%) patients attained disease stabilization. Median response dura tion was 7+ months (range 4 to 20+), and the median overall survival w as 12 months (range 4-23+). The regimen was well tolerated. WHO nausea /vomiting grades 1-2, alopecia grade 3, and neutropenia grades 1-2 wer e seen in most patients. Four patients experienced mild neuropathy, wh ile it was grade 3 in 1 case. Seven patients had grade 3 neutropenia. In addition, grade 4 neutropenia associated with fever was documented in other 4 cases. No hypersensitivity reactions were seen. One case of reversible tachycardia after drug administration was seen. Myalgia gr ades 1-2 was also reported in some patients. Conclusion. These results suggest that the present regimen has significant activity in heavily pretreated patients with a MBC, with a manageable toxicity profile. Fu rther trials exploiting the above mentioned drug combination are warra nted.