Welcome to PeerView

SECTION III: Second-Line Therapy

Abstract 205
Preliminary Results of a Phase II Randomized Trial of Docetaxel (Taxotere) as a Single-Agent Chemotherapy Administered Weekly or 3-Weekly in Patients with Metastatic Breast Cancer
Miguel A. Climent, MD, Instituto Valenciano de Oncologia, Valencia, Spain

Interim analysis of this phase II trial showed that Taxotere (docetaxel) has similar efficacy when given weekly or every three weeks, but weekly dosing had a better safety profile, with a lower incidence of neutropenia and neurotoxicity, compared to Taxotere given every three weeks.

"Both schedules of single-agent Taxotere result in similar antitumor activity. The schedules were well tolerated, although the toxicity profiles differed. Our findings suggest either schedule can be used, depending on patient preferences or schedule convenience," Dr. Miguel A. Climent reported at the 38^th annual ASCO meeting.

Every three-week Taxotere is commonly used in Europe. Studies have shown that Taxotere administered on an every three-week schedule achieves response rates ranging from 52% to 68% as first-line therapy and 30% to 58% as second-line therapy. Weekly Taxotere produces response rates from 33% to 50% in previously treated patients with metastatic breast cancer, Dr. Climent noted.

"Weekly Taxotere may increase the percentage of cell death and furthermore prevent tumor re-growth by acting against resistant cell subpopulations. Higher exposure to the drug seems to enhance this process. The weekly schedule allows prolonged treatment to a high cumulative dose with minor hematologic and neurologic toxicity," he continued.

The primary endpoint of this phase II trial was to compare the incidence of grade 3 and 4 adverse events with the use of the two schedules of single-agent Taxotere as second-line therapy in patients with metastatic breast cancer. The secondary endpoints were response rate, time to treatment failure, quality of life, response duration, time to progression, and survival.

Trial Design
The study population included 83 women aged 18 to 75 years (median age 55 years, range 25-72) with at least one measurable site of metastatic disease and performance status (PS) 2. All had previously received an anthracycline and/or alkylating agent either in the adjuvant or first-line metastatic setting. Previous paclitaxel (Taxol) chemotherapy was allowed. Sixty-six women (79.5%) were postmenopausal, 45 (64.3%) were estrogen receptor-positive (ER+), and 37 (52.9%) were progesterone receptor-positive (PR+). Forty-nine (59.1%) were Eastern Cooperative Oncology Group (ECOG) performance status 0, while 30 (36.1%) and three (3.6%) were ECOG 1 and 2, respectively.

Patients were randomized to one of two chemotherapy regimens:

Group A (n=41). Taxotere 40 mg/m² IV over 30-minutes weekly for six weeks followed by a two-week rest for two cycles;
Group B (n=42). Taxotere 100 mg/m² IV over one hour on day 1 every three weeks for six cycles.

Patients also received premedication with dexamethasone (Decadron, Aeroseb-Dex, Corotason, Curson, and others).

Toxicity
Significantly more patients experienced grade 3 and 4 neutropenia in the every three-week versus the weekly group — seven (17.9%) vs. one (2.5%), (p=0.057). Significantly more febrile neutropenia was also seen in the every three-week group — seven (17.9%) vs. two (5%), (p=0.088). More nausea, vomiting, stomatitis and diarrhea was seen in the every three-week group while fatigue, asthenia and tearing was more common with weekly therapy.

Efficacy
Response rates were similar between the two groups. The overall response rate was 43.9% (18 of 41 patients) in the weekly group and 38% (16 of 42 patients) in the every three-week group. Two women in each group achieved complete responses, and 12 in each group achieved a partial response. Time to treatment failure was 3.7 months with weekly therapy versus 4.4 months with every three-week administration.

Key Points In Focus:

Both weekly and three-weekly schedules of single-agent Taxotere as second-line therapy have similar response rates and antitumor activity.
Both schedules were well tolerated, although toxicity profiles differed. More grade 3 and 4 neutropenia and febrile neutropenia were observed in the every three-week Taxotere group compared with weekly Taxotere.
These findings suggest that either schedule can be used, depending on patient preference or schedule convenience.

--[ TOP ]--