Practical Aspects of Weekly Docetaxel Administration Schedules

Abstract

Docetaxel (Taxotere ®; Aventis Pharmaceuticals Inc.; Bridgewater, NJ) is a highly effective chemotherapeutic agent with proven efficacy in a number of solid tumors. However, myelosuppression can be a substantial concern when docetaxel is administered every 3 weeks. Myelosuppression can be particularly problematic in older patients and those being treated with palliative intent. Weekly dosing of docetaxel has been investigated in an effort to reduce toxicity and has been identified as a safe and effective regimen in clinical trials. Weekly docetaxel is generally administered at doses ranging from 30-40 mg/m 2 /week for 6 of 8 weeks or for 3 of 4 weeks. With weekly dosing, though efficacy is comparable, myelosuppression is substantially less, and the overall tolerability profile is better than with every-3-week dosing. Fatigue is a common toxicity associated with weekly docetaxel; other adverse effects that are seen in a minority of patients include hyperlacrimation, nail toxicity, and alopecia. These side effects are dose related and can generally be managed through dose reductions or alterations in the weekly schedule. Because of the favorable tolerability profile, weekly docetaxel is under investigation in combination with other chemotherapeutic agents and with novel targeted agents in a variety of tumor types. The results of these ongoing studies will further define the place of weekly docetaxel in cancer therapy. The Oncologist 2004;9:538-545 The Oncologist 2004;9:538-545 www.TheOncologist.com

High-Dose Calcitriol, Docetaxel and Zoledronic Acid in Patients with Castration-Resistant Prostate Cancer: A Phase II Study

“…Docetaxel as a single agent has shown good results in PSA reduction and survival at doses of 70–75 mg/m 2 every 3 weeks [13,14]. Weekly administration of docetaxel has been shown to have similar efficacy with less neutropenia than 3-weekly schedules [15]. Several phase II studies in CRPC have investigated weekly docetaxel, given at doses of 25–40 mg/m 2 in a variety of schedules [16,17,18].…”

Albumin-bound formulation of paclitaxel (Abraxane® ABI-007) in the treatment of breast cancer

“…antineoplastic activity against a wide variety of malignancies including also non-small-cell lung cancer and ovarian cancer. [12][13][14] Paclitaxel is a naturally occurring complex product extracted from the bark of the western yew (Taxus brevifolia) [15][16][17] and is widely used for the treatment of breast, lung, and advanced ovarian cancers 10,18,19 while docetaxel was originally isolated in a precursor form from the needles of the European yew. 20 The clinical advances of taxanes have been limited by their chemical formulation: they are highly hydrophobic molecules.…”

A phase I pharmacological and biological study of PI-88 and docetaxel in patients with advanced malignancies

“…Low dose weekly docetaxel was chosen due to its low incidence of severe myelosuppression (<15%), and thrombocytopenia (<5%) [7,23,28,43]. The principal toxicities in this study of fatigue, dysgeusia, diarrhea, and nausea/vomiting were in keeping with the toxicity profile of docetaxel, as was transient hyperbilirubinemia in one patient [21]; whereas, injection site bruising and thrombocytopenia were observed with PI-88.…”

“…Docetaxel, a semi-synthetic taxane, has established broad-spectrum anti-tumor activity in breast, lung, gastric, prostate and ovarian cancers at doses of 60-100 mg/m 2 IV administered every 3 weeks [7,21,22]. The high incidence of acute severe neutropenia, alopecia, asthenia, dermatological reactions, fluid retention, hypersensitivity reactions and stomatitis are reduced when dosing is changed to fixed low doses of 30-40 mg/m 2 given weekly [3,8].…”