Paclitaxel combined with ifosfamide in anthracycline- and docetaxel-pretreated metastatic breast cancer: activity independence of prior docetaxel resistance

• Published in: Cancer chemotherapy and pharmacology 2010-08, Vol.66 (3), p.425-431
• Main Authors: Moon, Yong Wha, Sohn, Joo Hyuk, Choi, Hye Jin, Chang, Hyun, Park, Byeong-Woo, Kim, Seung Il, Park, Seho, Koo, Ja Seung, Kim, Yong Tai, Roh, Jae Kyung, Chung, Hyun Cheol, Kim, Joo-Hang
• Format: Article
• Language: English
• Subjects: Adult; Aged; Anthracyclines - administration & dosage; Antineoplastic agents; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Cancer Research; Drug Resistance, Neoplasm; Female; Gynecology. Andrology. Obstetrics; Humans; Ifosfamide - administration & dosage; Mammary gland diseases; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Neoplasm Metastasis; Neutropenia - chemically induced; Oncology; Original Article; Paclitaxel - administration & dosage; Pharmacology. Drug treatments; Pharmacology/Toxicology; Retrospective Studies; Survival Rate; Taxoids - administration & dosage; Taxoids - pharmacology; Treatment Outcome; Tumors
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-009-1176-5

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. Conclusion 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.