Paclitaxel combined with ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer: activity independence of prior docetaxel resistance.
BACKGROUND
We evaluated the efficacy and tolerability of combined paclitaxel and ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer (MBC).


METHODS
Patients received paclitaxel (175 mg/m(2) i.v. in a 3-h infusion) on day 1 and ifosfamide (1.5 g/m(2) i.v. in a 15-min infusion) on days 1-3, every 3 weeks for a maximum of nine cycles. The tumor response was assessed every two cycles.


RESULTS
We enrolled 34 patients with a median age of 50 years. Thirty patients had visceral metastases. Anthracycline- and docetaxel-based chemotherapy had previously been administered to 18/13 and 13/21 patients, respectively, in (neo)adjuvant/metastatic settings. Three patients had not previously received anthracycline due to abnormal cardiac functions. A total of 174 cycles of chemotherapy were delivered with a median of six cycles. The response rate under the intent-to-treat analysis was 23.5% (all partial responses) with a median response duration of 14 months. The disease control rate was 70.6%. The median progression-free and overall survival were 5.9 and 8.5 months, respectively. There was no apparent relationship between activity and prior docetaxel resistance. The incidence of grade III/IV neutropenia was 46.6% (81 of 174 cycles) with febrile neutropenia of only 1.7%. Major grade III/IV non-hematological toxicities included peripheral neuropathy (6 of 34 patients) and infection (4 of 34 patients). There were no treatment-related deaths.


CONCLUSIONS
Paclitaxel combined with ifosfamide was effective and tolerable in anthracycline-/docetaxel-pretreated MBC. Overcoming docetaxel resistance by using paclitaxel in combination with ifosfamide needs to be addressed through further investigation.
Moon
Yong Wha
YW
Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, 250 Seongsanno, Seodaemun-gu, Seoul, 120-752, Korea.
Sohn
Joo Hyuk
JH
Choi
Hye Jin
HJ
Chang
Hyun
H
Park
Byeong-Woo
BW
Kim
Seung Il
SI
Park
Seho
S
Koo
Ja Seung
JS
Kim
Yong Tai
YT
Roh
Jae Kyung
JK
Chung
Hyun Cheol
HC
Kim
Joo-Hang
JH
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D017239:Paclitaxel / Q000008:administration & dosage; D012189:Retrospective Studies; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology; D016896:Treatment Outcome
D018943:Anthracyclines; D043823:Taxoids; D000077143:Docetaxel; D017239:Paclitaxel; D007069:Ifosfamide