Phase II Trial of Taxol, an Active Drug in the Treatment of Metastatic Breast Cancer

Abstract

Taxol, an antimicrotubule agent, has shown promise for efficacy in treatment of breast cancer, but severe hypersensitivity reactions led to cessation of many phase I clinical trials. Consequently, investigators and the National Cancer Institute recommended that phase I and II studies of this agent use 24-hour infusions and antiallergic medications. Using a premedication regimen effective in preventing hypersensitivity reactions, we have performed a phase II trial of taxol in patients with metastatic breast cancer. Taxol was administered to 25 patients at a dose of 250 mg/m2 by 24-hour infusion every 21 days. These patients had received only one prior chemotherapy regimen, either adjuvant to surgery or for metastatic disease; all but two had received doxorubicin. In 60% of the patients, the dominant site of disease was the viscera. All patients were assessable. In April 1991, at a median time on study of 9 months (range, 5-13+ months), the objective response rate was 56% (12% complete and 44% partial; 95% confidence interval, 35%-76%). Disease progressed in only 8% of the patients. The median number of courses of therapy was 11. Granulocytopenia was the dose-limiting toxic effect, but neutropenia with fever occurred in only 5% of 232 courses. A chronic glove-and-stocking neuropathy developed in most patients, but no allergic reactions occurred. We conclude that taxol is an active agent in the treatment of metastatic breast cancer and that it warrants continued study. Currently, we are conducting a phase I trial of taxol plus doxorubicin. Future trials should address the optimal effective dose, the optimal sequencing of combinations, mechanisms of drug resistance in tumors, and dose-limiting toxic effects (particularly cardiac toxic effects of taxol given as a single agent or in drug combinations).

Paclitaxel-resistant Human Ovarian Cancer Cells Have Mutant β-Tubulins That Exhibit Impaired Paclitaxel-driven Polymerization

“…Paclitaxel (PTX) 1 is a complex diterpene (1), active against a broad range of human tumors, including ovarian and breast carcinomas (2)(3)(4). The primary target of PTX is the microtubule (MT), which is vital for mitosis, motility, secretion, and proliferation (5).…”

Phase I/II study of S-1 combined with paclitaxel in patients with unresectable and/or recurrent advanced gastric cancer

“…Paclitaxel, a newer taxane, has been shown to be effective against a variety of cancers, including breast cancer (Holmes et al, 1991), ovarian cancer (Einzig et al, 1992), and lung cancer (Chang et al, 1993). Paclitaxel is also an effective drug for gastric cancer, with response rates ranging from 20 to 28% in single-agent phase II studies (Ajani et al, 1998;Ohtsu et al, 1998;Yamada et al, 2001;Yamaguchi et al, 2002).…”

Delayed expression of apoptosis in human lymphoma cells undergoing low-dose taxol-induced mitotic stress

“…This naturally occurring agent has been shown to have significant activity against advanced ovarian cancers (McGuire et al, 1989;Runowicz et al, 1995), metastatic breast cancers (Holmes et al, 1991;Hortobagyi and Holmes, 1996), and leukaemias refractory to standard chemotherapy. It has also shown some activity against various other tumour types (Etlinger, 1993;Forastiere, 1993;Einzig and Wiernik, 1995;Edelman and Gandara, 1996).…”