Adjuvant Docetaxel for Node-Positive Breast Cancer
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《新英格兰医药杂志》
To the Editor: The study by Martin et al. (June 2 issue)1 raises concern about the high rates of febrile neutropenia among patients receiving a regimen of docetaxel plus doxorubicin and cyclophosphamide (TAC). Moreover, it is not clear that the right comparator is a regimen of fluorouracil plus doxorubicin and cyclophosphamide (FAC). Dose-dense regimens have been shown to be effective and less toxic.2 A recent study was prematurely terminated because of an unacceptable rate of life-threatening sepsis associated with adjuvant doxorubicin plus docetaxel.3 We think that docetaxel-based adjuvant chemotherapy cannot be advocated as a standard approach in the management of node-positive breast cancer.
Manmeet S. Ahluwalia, M.D.
Fairview Hospital
Cleveland, OH 44111
Hamed A. Daw, M.D.
Cleveland Clinic Cancer Center
Cleveland, OH 44111
dawh@ccf.org
References
Martin M, Pienkowski P, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005;352:2302-2313.
Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003;21:1431-1439.
Brain EG, Bachelot T, Serin D, et al. Life-threatening sepsis associated with adjuvant doxorubicin plus docetaxel for intermediate-risk breast cancer. JAMA 2005;293:2367-2371.
To the Editor: In the trial conducted by Martin et al., grade 3 or 4 neutropenia occurred in 65.5 percent of patients in the experimental TAC group; febrile neutropenia occurred in 24.7 percent. The authors state that "The rates of febrile neutropenia did not reach the recommended threshold for routine prophylactic administration of G-CSF [granulocyte colony-stimulating factor]." Although this is, strictly speaking, true, the American Society of Clinical Oncology recommends that the prophylactic administration of growth factor may be considered if prolonged neutropenia results in treatment delays or dose reduction.1 In the current trial, one third of the patients required a treatment delay or dose modification. It is increasingly recognized that for adjuvant therapy in breast cancer, maintaining the dose intensity leads to improved treatment efficacy2; indeed, there is evidence that dose-dense regimens are more efficacious than regimens administered at conventional intervals.3 Prophylactic growth-factor support could help to ameliorate treatment delays, maintain dose intensity, and possibly enhance efficacy, and should therefore be routinely considered for patients receiving either TAC or FAC.
Vanita Noronha, M.B., B.S.
Yale University School of Medicine
New Haven, CT 06520
vanita.noronha@gmail.com
References
Ozer H, Armitage JO, Bennett CL, et al. 2000 Update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol 2000;18:3558-3585.
Budman DR. Dose and schedule as determinants of outcomes in chemotherapy for breast cancer. Semin Oncol 2004;31:Suppl 15:3-9.
Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003;21:1431-1439.
The authors reply: Our study protocol mandated the prophylactic administration of G-CSF after the first episode of febrile neutropenia in the TAC group. With this approach, 25 percent of the patients treated with TAC had febrile neutropenia; there were, however, no fatal infections. Many episodes of neutropenic fever occurred in the first cycle of TAC. A subsequent study by the Spanish Breast Cancer Research Group (GEICAM), carried out in patients with node-negative breast cancer and with the same design as ours (six cycles of FAC vs. six cycles of TAC), also reported a rate of neutropenic fever of 25 percent among patients in the TAC group. Their protocol was amended to allow prophylaxis with G-CSF starting with the first cycle of TAC. This change reduced the incidence of neutropenic fever to 6.5 percent in the TAC group.1
Drs. Ahluwalia and Daw mention a recently published study comparing doxorubicin plus cyclophosphamide with doxorubicin plus docetaxel as adjuvant therapy for breast cancer.2 The acute mortality reported in this study (0.63 percent; 95 percent confidence interval, 0.24 to 1.02 percent) does not seem to be representative of our experience with the docetaxel–doxorubicin combination, which includes data from the treatment of more than 2900 patients,1 and unpublished data. The incidence of treatment-related death from any cause in these trials did not exceed 0.2 percent (95 percent confidence interval, 0.19 to 0.21 percent), with only one death from sepsis.
We now recommend that G-CSF be given as a primary prophylaxis for patients receiving TAC and other related regimens. This recommendation is in accordance with the 2005 National Comprehensive Cancer Network guidelines, which suggest prophylactic G-CSF support for regimens associated with a rate of febrile neutropenia of more than 20 percent.
Miguel Martin, M.D.
Hospital Universitario San Carlos
28040 Madrid, Spain
mmartin@geicam.org
Charles Vogel, M.D.
Cancer Research Network
Plantation, FL 33324
for the Breast Cancer International Research Group
Since publication of the report, Dr. Martin reports having served as consultant for and having received speaker's fees from PharmaMar and Pfizer.
Manmeet S. Ahluwalia, M.D.
Fairview Hospital
Cleveland, OH 44111
Hamed A. Daw, M.D.
Cleveland Clinic Cancer Center
Cleveland, OH 44111
dawh@ccf.org
References
Martin M, Pienkowski P, Mackey J, et al. Adjuvant docetaxel for node-positive breast cancer. N Engl J Med 2005;352:2302-2313.
Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003;21:1431-1439.
Brain EG, Bachelot T, Serin D, et al. Life-threatening sepsis associated with adjuvant doxorubicin plus docetaxel for intermediate-risk breast cancer. JAMA 2005;293:2367-2371.
To the Editor: In the trial conducted by Martin et al., grade 3 or 4 neutropenia occurred in 65.5 percent of patients in the experimental TAC group; febrile neutropenia occurred in 24.7 percent. The authors state that "The rates of febrile neutropenia did not reach the recommended threshold for routine prophylactic administration of G-CSF [granulocyte colony-stimulating factor]." Although this is, strictly speaking, true, the American Society of Clinical Oncology recommends that the prophylactic administration of growth factor may be considered if prolonged neutropenia results in treatment delays or dose reduction.1 In the current trial, one third of the patients required a treatment delay or dose modification. It is increasingly recognized that for adjuvant therapy in breast cancer, maintaining the dose intensity leads to improved treatment efficacy2; indeed, there is evidence that dose-dense regimens are more efficacious than regimens administered at conventional intervals.3 Prophylactic growth-factor support could help to ameliorate treatment delays, maintain dose intensity, and possibly enhance efficacy, and should therefore be routinely considered for patients receiving either TAC or FAC.
Vanita Noronha, M.B., B.S.
Yale University School of Medicine
New Haven, CT 06520
vanita.noronha@gmail.com
References
Ozer H, Armitage JO, Bennett CL, et al. 2000 Update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. J Clin Oncol 2000;18:3558-3585.
Budman DR. Dose and schedule as determinants of outcomes in chemotherapy for breast cancer. Semin Oncol 2004;31:Suppl 15:3-9.
Citron ML, Berry DA, Cirrincione C, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol 2003;21:1431-1439.
The authors reply: Our study protocol mandated the prophylactic administration of G-CSF after the first episode of febrile neutropenia in the TAC group. With this approach, 25 percent of the patients treated with TAC had febrile neutropenia; there were, however, no fatal infections. Many episodes of neutropenic fever occurred in the first cycle of TAC. A subsequent study by the Spanish Breast Cancer Research Group (GEICAM), carried out in patients with node-negative breast cancer and with the same design as ours (six cycles of FAC vs. six cycles of TAC), also reported a rate of neutropenic fever of 25 percent among patients in the TAC group. Their protocol was amended to allow prophylaxis with G-CSF starting with the first cycle of TAC. This change reduced the incidence of neutropenic fever to 6.5 percent in the TAC group.1
Drs. Ahluwalia and Daw mention a recently published study comparing doxorubicin plus cyclophosphamide with doxorubicin plus docetaxel as adjuvant therapy for breast cancer.2 The acute mortality reported in this study (0.63 percent; 95 percent confidence interval, 0.24 to 1.02 percent) does not seem to be representative of our experience with the docetaxel–doxorubicin combination, which includes data from the treatment of more than 2900 patients,1 and unpublished data. The incidence of treatment-related death from any cause in these trials did not exceed 0.2 percent (95 percent confidence interval, 0.19 to 0.21 percent), with only one death from sepsis.
We now recommend that G-CSF be given as a primary prophylaxis for patients receiving TAC and other related regimens. This recommendation is in accordance with the 2005 National Comprehensive Cancer Network guidelines, which suggest prophylactic G-CSF support for regimens associated with a rate of febrile neutropenia of more than 20 percent.
Miguel Martin, M.D.
Hospital Universitario San Carlos
28040 Madrid, Spain
mmartin@geicam.org
Charles Vogel, M.D.
Cancer Research Network
Plantation, FL 33324
for the Breast Cancer International Research Group
Since publication of the report, Dr. Martin reports having served as consultant for and having received speaker's fees from PharmaMar and Pfizer.