Improved Outcomes From Adding Sequential Paclitaxel but Not From Escalating Doxorubicin Dose in an Adjuvant Chemotherapy Regimen for Patients With Node-Positive Primary Breast Cancer
- Study type
- Clinical trial
- Study name
- CALGB 9344
- Design
- Randomised trial; three doxorubicin dose levels, followed by either no further therapy or the addition of paclitaxel
- Sample size
- 3121 women
- Source
- JCO · 2003
In plain words
In this large study, women with breast cancer that had spread to the lymph nodes received chemotherapy after surgery. Raising the dose of one of the drugs (doxorubicin) did not help. But adding four cycles of the drug paclitaxel after standard chemotherapy lowered the chance of the cancer coming back and of death, and its extra side effects were generally small.
Key results
Treatment arms and regimens
Cyclophosphamide (C) 600 mg/m² with one of three doxorubicin (A) doses, 60, 75 or 90 mg/m², for four cycles; then no further therapy.
Doxorubicin 60 mg/m² (day 1), or 75 mg/m² (in two doses on days 1 and 2), or 90 mg/m² (in two doses on days 1 and 2 with prophylactic G-CSF and ciprofloxacin) + cyclophosphamide 600 mg/m², every 3 weeks for 4 cycles. Tamoxifen 20 mg daily for 5 years in receptor-positive tumours.
Cyclophosphamide 600 mg/m² with doxorubicin 60, 75 or 90 mg/m² for four cycles, followed by four cycles of paclitaxel 175 mg/m².
The same AC every 3 weeks for 4 cycles, then paclitaxel 175 mg/m² as a 3-hour infusion every 3 weeks for 4 cycles; tamoxifen 20 mg daily for 5 years in receptor-positive tumours.
Source of the regimen details: FDA label for paclitaxel (DailyMed, Clinical Studies section, Intergroup/CALGB trial) and the abstract of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Women with operable, node-positive breast cancer enrolled after surgical treatment. 94% of patients with hormone receptor-positive tumours received tamoxifen.
Endpoints
The study aimed to determine whether escalating the doxorubicin dose or adding paclitaxel to standard adjuvant chemotherapy for breast cancer prolongs time to recurrence and survival. Reported outcomes included disease-free survival, overall survival and toxicity.
Safety and side effects
The additional toxicity of adding four cycles of paclitaxel was generally modest. Exact rates of grade 3 or higher adverse events are not reported in the abstract.
Clinical significance and place in guidelines
This study shows that escalating the doxorubicin dose is of no benefit, whereas adding four cycles of paclitaxel after CA improves disease-free and overall survival in node-positive early breast cancer. The benefit appeared greater in oestrogen receptor-negative tumours, but this finding comes from an unplanned analysis. The current place of this regimen in guidelines, and the choice of regimen for each patient, should be checked against up-to-date guidelines.
Limitations
The difference in paclitaxel effect by oestrogen receptor status comes from an unplanned subgroup analysis, and no significant difference was seen in the protocol-defined subgroups; this finding is therefore hypothesis-generating. Exact rates of grade 3 or higher adverse events are not reported in the abstract.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.