The Cancer And Leukemia Group B (CALGB) is is a national clinical research group sponsored by the National Cancer Institute, with its Central Office headquartered at the University of Chicago and its Statistical Center located at Duke University. The CALGB was founded in 1955 with a goal of bringing together clinical oncologists and laboratory investigators to develop better treatments for cancer. Since then, CALGB has grown into a national network of 29 university medical centers, over 185 community hospitals and more than almost 3000 physicians who collaborate in clinical research studies aimed at reducing the morbidity and mortality from cancer, relating the biological characteristics of cancer to clinical outcomes and developing new strategies for the early detection and prevention of cancer.
CALGB Protocol 8541 (CALGB 8541) was a randomized clinical trial comparing three doses (high, moderate, and low) of chemotherapy (cyclophosphamide, doxorubicin, also known as adriamycin, and 5 fluorouracil, abbreviated CAF) in 1572 women with early stage, node-positive breast cancer. A main goal of the study was to determine if the dose and regimen of chemotherapy is related to survival. Patients were randomized to three different regimens:
1. Intensive CAF
600 mg/m2 IV Day 1 cyclophosamide
60 mg/m2 IV Day 1 doxorubicin
600 mg/m2 IV Days 1, 8 5 florouracil
Repeated every 28 days for 4 cycles
2 . Low dose CAF
300 mg/m2 IV Day 1 cyclophosamide
30 mg/m2 IV Day 1 doxorubicin
300 mg/m2 IV Days 1, 8 5 florouracil
Repeated every 28 days for 4 cycles
3. Standard (moderate) dose CAF
400 mg/m2 IV Day 1 cyclophosamide
40 mg/m2 IV Day 1 doxorubicin
400 mg/m2 IV Days 1, 8 5 florouracil
Repeated every 28 days for 6 cycles
Regimens 1 and 3 deliver the same overall cumulative dose of CAF, but
the first regimen does so over a shorter period. Regimen 2 delivers
half this dose. Objectives were to compare regimens 1 and 2 (high or low
dose over the same 4 cycle period) and to contrast these against
the standard of high dose administered over 6 cycles.Women entered into the study with histologically confirmed adenocarcinoma of the breast (i.e., with a breast cancer tumor) that may have been treated by mastectomy or lumpectomy.
Data on 1479 eligible patients available to us after long-term follow-up include the variables:
days total number of days followed
cens =0 if the patient was censored after the indicated number of days
=1 if the patient died after the indicated number of days
trt =1,2,3 according to regimen received by the patient
meno =0 if the woman was pre-menopausal, = 1 otherwise
tumsize size of breast cancer tumor (cm)
nodes number of histologically positive lymph nodes found
er estrogen receptor protein (ERP) status (=0 if negative,
=1 if positive)
References
The primary analysis was reported after a median of 3.4 years of follow-up. Women treated with the high or moderate dose intensity had significantly longer disease-free survival (P<0.001) and overall survival (P = 0.004) than those treated with the low dose using the log-rank test. However, the difference in survival between the two groups treated with a moderate or high dose was not significant. The analysis is reported in
Wood WC, Budman DR, Korzun AH et al. Dose and dose intensity of adjuvant chemotherapy for stage-II, node-positive breast-carcinoma. N Engl J Med. 1994; 330:1253-1259.