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

Purpose. Treatment results in patients failing first-line chemotherapy inmetastatic breast cancer (MBC) are still unsatisfactory, with patientsexhibiting poor responses to salvage therapy and a short overall survival.Both paclitaxel and ifosfamide are able to produce objective tumor responsesin the disease. Therefore, the antitumor effects and toxicity of theircombined use could be worthwhile studying in patients progressing afterdoxorubicin-containing combinations. Patients and methods: This Phase IItrial of paclitaxel/ifosfamide included patients with bi-dimensionallymeasurable metastatic breast cancer in second or third relapse, followinganthracycline-containing regimens: ECOG PS <2, and adequate hepatic,cardiac renal and hematological functions. Paclitaxel 175 mg/m2 was given onday 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/m2i.v., 15 minutes before and 4 hours after ifosfamide administration, and 720mg/m2 P.O. 8 hours later at home, also on days 2, 3, 4. The cycles wererepeated every 21 days, on an outpatient basis. Results. Twenty-fourpatients were accrued for the study and 23 were considered eligible for theevaluation of toxicity ans response. Previous chemotherapy included: CMF/FAC(16 cases); CMF plus mitoxantrone/FAC/cisplatin, vinblastine, mitomycin C (2cases); and FAC/mitomycin C, vinblastine, and etoposide (5 cases). Therewere 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%) patientsattained disease stabilization. Median response duration was 7+ months(range 4 to 20+), and the median overall survival was 12 months (range4-23+). 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 neutropeniaassociated with fever was documented in other 4 cases. No hypersensitivityreactions were seen. One case of reversible tachycardia after drugadministration was seen. Myalgia grades 1-2 was also reported in somepatients. Conclusion. These results suggest that the present regimen hassignificant activity in heavily pretreated patients with a MBC, with amanageable toxicity profile. Further trials exploiting the above mentioneddrug combination are warranted.