Dose Intensity of Standard Adjuvant CMF with Granulocyte Colony-Stimulating Factor for Premenopausal Patients with Node-Positive Breast Cancer

Abstract

The effects of granulocyte colony-stimulating factor (G-CSF) on total dose and dose intensity of standard oral adjuvant CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy were studied in premenopausal patients with node-positive breast cancer. Treatment consisted of standard CMF and locoregional radiotherapy (on indication). G-CSF was administered if the leukocyte count recovery was insufficient. Fifty-one patients required no G-CSF (‘no cytopenia’), and 50 patients received G-CSF (‘G-CSF’). Twenty-two patients, however, received no G-CSF support despite insufficient leukocyte recovery (‘control’). Following G-CSF, leukocyte recovery was adequate in 83% of the chemotherapy cycles. The proportion of the patients who had a dose intensity > 85% was 90% in the ‘no cytopenia’ group, 74% in the ‘G-CSF’ group, and 45% in the ‘control’ group (p < 0.05). Leukocyte recovery was adequate in 87% of the chemotherapy cycles in the patients who received radiotherapy as compared with 92% of those in the patients without radiotherapy (p < 0.05). In conclusion an adequate leukocyte recovery after G-CSF was found in 83% of all chemotherapy cycles. The dose intensity of the G-CSF group was higher as compared with controls. The impact of radiotherapy on hematological recovery was significant, but not dependent on G-CSF.

True

“…This would have resulted in 19 patients (83%) with delay of treatment and an estimated achieved DI of 84% at most. The effect of G-CSF on DI of standard oral adjuvant CMF in 123 patients with breast cancer was studied by De Graaf et al Without G-CSF the leucocyte count on day one was ≤ 3 × 10 9 l -1 in 21% of the courses (De Graaf et al, 1996). In our study, the leucocyte count was ≤ 3 × 10 9 l -1 in 32% of the courses.…”

“…Several investigators showed that radiotherapy could have a negative effect on marrow recovery and on the dose intensity in combination with chemotherapy (Holland et al, 1980;Cooper et al, 1981;Levine et al, 1984;De Graaf et al, 1996). This was especially seen when G-CSF was administered in conjunction with the radiotherapy, leading to additional delays for thrombocytopenia.…”

“…G-CSF stimulates the recovery of granulocytes after chemotherapy. G-CSF has been used to enhance dose intensity by shortening the interval between cycles or by increase in dosage (Bronchud et al, 1989;Neidhart et al, 1989;Crawford et al, 1991;Lieschke and Burgess, 1992;Biesma et al, 1992;De Graaf et al, 1996;Ribas et al, 1996).…”

The Geriatric Cancer Patient

“…Numerous studies, particularly in breast cancer and NHL, have established that long-term survival may be compromised if the total dose or relative dose intensity falls below a threshold value. [10][11][12][13][14] A superior alternative to dose modification may be the prophylactic use of granulocyte colony-stimulating factor (G-CSF), which has been shown to reduce the severity and duration of chemotherapy-induced neutropenia, 15,16 thereby minimizing the need for dose modifications [16][17][18] and the risk of a compromised outcome due to suboptimal delivery of the chemotherapy. This strategy may be particularly beneficial in elderly patients, who generally have increased susceptibility to, and poorer recovery from, myelotoxic effects.…”

“…The percentage of women in each group in whom the relative dose intensity was less than 85% was calculated, and a failure to maintain at least 85% relative dose intensity was seen in only 26% of the women who were given G-CSF but in 55% of those who were given placebo (P < 0.05). 17 This study was not specifically designed to compare the benefits in older and younger women, but an earlier study had already shown that older and younger patients derive comparable benefits from G-CSF prophylaxis against chemotherapy-induced neutropenia. 45 The conclusions on breast cancer in older women are similar to those on other forms of cancer in the elderly.…”