Treatment of metastatic breast cancer with combination paclitaxel/cyclophosphamide.
Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) has demonstrated substantial single-agent activity against both minimally pretreated and resistant metastatic breast cancer. Evaluation of paclitaxel-based combinations has demonstrated appreciable activity, but also toxicity, for the paclitaxel/doxorubicin combination. The paclitaxel/cyclophosphamide combination is potentially attractive because of the significant single-agent activity of both drugs against metastatic breast cancer and the paucity of shared nonhematologic toxicities. This combination is being evaluated in women with doxorubicin-refractory metastatic breast cancer. Dose escalation to paclitaxel 200 mg/m2 over 24 hours and cyclophosphamide 2,000 mg/m2 administered every 21 days with granulocyte colony-stimulating factor support has been performed. The final dose level was complicated by dose-limiting toxicity. The maximum tolerated dose for this combination is currently being defined. There is preliminary evidence of sequence-dependent toxicity. Grade 4 neutropenia and neutropenic fevers are more frequent in cycles in which paclitaxel is administered first.
Kennedy
M J
MJ
Johns Hopkins Oncology Center, Baltimore, MD 21287, USA.
Donehower
R C
RC
Rowinsky
E K
EK
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D003520:Cyclophosphamide / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D004334:Drug Administration Schedule; D004351:Drug Resistance; D005260:Female; D005334:Fever / Q000139:chemically induced / Q000517:prevention & control; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced / Q000517:prevention & control; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D012074:Remission Induction
D016179:Granulocyte Colony-Stimulating Factor; D004317:Doxorubicin; D003520:Cyclophosphamide; D017239:Paclitaxel