Phase II trial of paclitaxel and ifosfamide as a salvage treatment in metastatic breast cancer.

OBJECTIVE

Treatment results in patients failing first-line chemotherapy in metastatic breast cancer (MBC) are still unsatisfactory, with patients 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 patients progressing after doxorubicin-containing combinations.

METHODS

This Phase II trial of paclitaxel/ifosfamide included patients with bi-dimensionally measurable metastatic breast cancer in second or third relapse, following anthracycline-containing regimens; ECOG PS < 2, and adequate hepatic, cardiac, renal, and hematological functions. 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 was given on days 2, 3, 4 with mesna 360 mg/m2 i.v., 15 minutes before and 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 accrued for the study and 23 were considered eligible for the evaluation of toxicity and response. Previous chemotherapy included: CMF/FAC (16 cases); CMF plus mitoxantrone/FAC/cisplatin, vinblastine, mitomycin C (2 cases): and FAC/mitomycin C, vinblastine, and etoposide (5 cases). There 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). Five (22%) patients attained disease stabilization. Median response duration was 7+ months (range 4 to 20+), and the median overall survival was 12 months (range 4-23+). The regimen was well tolerated. WHO nausea/ vomiting grades 1-2, alopecia grade 3, and neutropenia grades 1-2 were seen in most patients. Four patients experienced mild neuropathy, while 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 grades 1-2 was also reported in some patients.

CONCLUSIONS

These results suggest that the present regimen has significant activity in heavily pretreated patients with a MBC, with a manageable toxicity profile. Further trials exploiting the above mentioned drug combination are warranted.