Docetaxel is active in patients with paclitaxel-resistant breast cancer, particularly in those who failed to respond to brief infusions of paclitaxel. Response rates were comparable to or better than those seen with other therapies for patients with paclitaxel-resistant MBC. This confirms preclinical studies, which indicated only partial cross-resistance between paclitaxel and docetaxel.
Liposomal annamycin (L-AN) has shown antitumor activity in preclinical studies. It may selectively target tumors and bypass MDR-1 resistance. A total of 13 women with doxorubicin-resistant breast cancer were treated on this phase II study. The median number of prior chemotherapy regimens was two, and six patients had two or more organ sites of involvement. L-AN was administered at 190-250 mg/m(2) as an i.v. infusion over 1-2 h every 3 weeks. No responses were observed. Of the 13 patients, 12 had clear deterioration and new tumor growth after one or two courses. The 13th patient had prolonged grade 2 thrombocytopenia after one course, and was taken off study when the lung metastases increased 62 days after treatment. L-AN at this dose and on this schedule had no detectable antitumor activity in patients with doxorubicin-resistant metastatic breast cancer.
retrospective analysis, the authors evaluated the incidence of neutropenic fever, fever (41 episodes among 40 patients). The incidence of neutropenic fever did not Anderson Cancer Center, Houston, Texas.increase until the absolute neutrophil count (ANC) had decreased to less than 500/ mL, and then fever incidence had a linear relationship with decreasing ANC (linear trend, P õ 0.01). A source of infection was documented in 59% of the neutropenic fever episodes. The incidence of infection did not increase significantly until the ANC had decreased to less than 250/mL (P õ 0.01). The risk of neutropenic fever and infection was also significantly higher when patients had poor performance status or were undergoing the initial courses of chemotherapy. Patients with bone marrow metastases also had a higher frequency of fever, infection, and death, but these differences were not statistically significant.
CONCLUSIONS.For patients with metastatic breast carcinoma receiving salvage chemotherapy, the risk of fever increases with decreasing ANC, but the risk of infection does not increase significantly until ANC decreases to less than 250/ mL. ship between infections and neutropenia was first described about 30 years ago in patients with acute leukemia receiving chemotherapy. 2Received July 29, 1996; revision received November 20, 1996; accepted November 20, 1996.Since then, considerable progress has been made in the management ᭧ 1997 American Cancer Society
Docetaxel can be administered to patients with metastatic breast cancer and liver dysfunction after dose attenuation. However, because of a narrow therapeutic index in this clinical setting, therapy should be closely monitored with subsequent dose escalation when possible.
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