Weekly Taxotere for Lung Cancer
Abstract & Commentary
Synopsis: Weekly docetaxel was compared with the traditional every 3-week schedule in patients with advanced lung cancer after failure with a platinum-based regimen. There was no significant difference in efficacy in terms of time to progression or overall survival, but neutropenia was significantly more common for those receiving the drug at 3-week intervals. In contrast, asthenia was more common in the weekly treated patients. This may be due to the more sustained exposure to corticosteroid premedication.
Source: Gervais R, et al. Ann Oncol. 2005;16:90-96.
Docetaxel administered at a dose of 75 mg/m2 every 3 weeks is considered a standard second line approach for patients with non-small-cell carcinoma (NSCLC) of the lung when discovered to have progressive disease after initial platinum-based chemotherapy. Weekly docetaxel at a lower dose is also used in this setting and may be less toxic. Gervais and colleagues from Strasbourg randomized 125 patients with locally advanced or metastatic NSCLC after failure of a previous platinum-based regimen to receive either docetaxel 75 mg/m2 administered every 3 weeks or docetaxel 40 mg/m2 given weekly for 6 weeks followed by 2 weeks of rest.
Median time to progression and survival were similar between the 2 groups (2.1 and 5.8 months for the q3W arm compared to 1.8 and 5.5 months for the qW group). However, grade 3-4 neutropenia occured in 48.4% of the q3W treated patients vs 15.9% of the qW patients (P = 0.001). In addition, febrile neutropenia was observed in 6.5% of patiens in the q3W arm vs 0% in the qW arm. In contrast, asthenia was more frequent in the qW group.
Thus, weekly docetaxel is an alternative second-line approach for the treatment of NSCLC, comparable in efficacy to q3W dosing but with less resultant neutropenia.
Comment by William B. Ershler, MD
Docetaxel has become widely used for a variety of malignant conditions including lung, breast, and prostate cancer. For lung cancer, it is most frequently used as a second-line agent and in a q 3 week schedule. However, it has been widely appreciated, if not scientifically demonstrated, that weekly treatment is comparable in efficacy and less toxic. Thus, the findings of Gervais et al come as no surprise, albeit the difference with regard to neutropenia was a bit more than expected.
The profile of tumors for which docetaxel is active includes those common in elderly patients (lung, prostate, and breast). Older people are known to have compromised marrow reserve and more frequent episodes of neutropenia. Thus, weekly therapy may well be most effective in this setting. In this regard, the increased asthenia observed with weekly therapy is of concern, because this, also, is likely to be more of a problem for elderly patients. The asthenia may be the result of the common practice of premedicating with corticosteroids. On this trial, those randomized to weekly therapy were to receive 8 mg of dexamethsone (or comparable prednisone or methylprednisilone) on 3 occasions with each weekly dose of docetaxel. Although this was less than the 6 doses given to those on the q3W schedule, over the course of 6 weeks, this amounts fairly high dose, sustained corticosteroid treatment. It is quite possible that the higher incidence of asthenia is thereby explained. Currently, the Geriatric Oncology Consortium is investigating the level of steroid needed to prevent adverse consequences (fluid retention) in lung cancer patients receiving weekly docetaxel therapy.
William B. Ershler, MD, INOVA Fairfax Hospital Cancer Center, Fairfax, VA; Director, Institute for Advanced Studies in Aging, Washington, DC, is Editor for Clinical Oncology Alert.