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

Oncology ◽  
1996 ◽  
Vol 53 (4) ◽  
pp. 289-294 ◽  
Author(s):  
Hiltje de Graaf ◽  
Pax H.B. Willemse ◽  
Barbara Bong ◽  
Henk Piersma ◽  
Tonnis Tjabbes ◽  
...  
1996 ◽  
Vol 14 (5) ◽  
pp. 1573-1580 ◽  
Author(s):  
A Ribas ◽  
J Albanell ◽  
J Bellmunt ◽  
L A Solé-Calvo ◽  
B Bermejo ◽  
...  

PURPOSE To analyze the safety and efficacy of a short course of granulocyte colony-stimulating factor (G-CSF) to maintain dose-intensity of subsequent cycles of chemotherapy after a prior episode of prolonged neutropenia, without febrile complications, in patients receiving adjuvant treatment for breast cancer. PATIENTS AND METHODS Thirty-two patients undergoing adjuvant cyclophosphamide, methotrexate, and fluorouracil (CMF) or doxorubicin-CMF for stages I to II breast cancer were included after having chemotherapy delays due to neutropenia (absolute neutrophil count [ANC] < 1.5 x 10(9)/L) on day 22. G-CSF was administered subcutaneously on days 15 to 19 of each subsequent cycle. RESULTS None of the patients included in this study had to be admitted to the hospital for fever and neutropenia. The median percentage of the projected dose-intensity for CMF or doxorubicin-CMF on an intent-to-treat basis was 0.994, which was significantly higher than the delivered dose-intensity before the start of G-CSF treatment (P < .0001). Patients who received concomitant G-CSF and radiotherapy achieved a similar dose-intensity as patients who did not undergo radiotherapy. Seven patients discontinued G-CSF treatment due to musculoskeletal pain. These patients had more subsequent cycle delays because of day 22 neutropenia than the 25 patients who followed the G-CSF schedule (P = .0028). CONCLUSION A 5-day course of G-CSF in patients with prior chemotherapy delays due to prolonged neutropenia seems to be a safe and cost-effective schedule to maintain CMF or doxorubicin-CMF dose-intensity in the adjuvant treatment of breast cancer.


1997 ◽  
Vol 15 (4) ◽  
pp. 1367-1376 ◽  
Author(s):  
R I Lalisang ◽  
J A Wils ◽  
H W Nortier ◽  
J T Burghouts ◽  
P S Hupperets ◽  
...  

PURPOSE A potential application of hematopoietic growth factors is to obtain an increased dose-intensity. This can be achieved by either higher doses of chemotherapy with standard intervals, or by standard doses with shorter intervals. The potential of these approaches has not been investigated systematically. PATIENTS AND METHODS In a randomized, multicenter study, 49 advanced breast cancer patients were treated with granulocyte colony-stimulating factor (G-CSF) and either increasing doses of epirubicin and cyclophosphamide with fixed intervals (arm one) or progressively shorter intervals with fixed doses of epirubicin and cyclophosphamide (arm two). A cohort of at least six patients was studied at each interval/dose. A more intensified interval/dose was given if less than 50% of patients encountered a dose-intensity limiting criterium (DILC) in the first three courses. RESULTS In arm one, epirubicin 140 mg/m2 and cyclophosphamide 800 mg/m2 every 21 days was too toxic. Subsequently, epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 was tested with two of 10 patients encountering a DILC. All initial DILCs consisted of febrile neutropenia. In arm two, epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely with 14- and 12-day intervals. In the 10-day interval, eight of 12 patients completed the first three cycles without a DILC. In the 8-day interval, seven of eight patients encountered a DILC. Incomplete neutrophil recovery, and to a lesser extent stomatitis, were dose-limiting. CONCLUSION In combination with G-CSF, epirubicin 120 mg/m2 and cyclophosphamide 700 mg/m2 every 21 days was feasible (projected dose-intensity, 40 mg/m2/wk and 233 mg/m2/wk, respectively). Epirubicin 75 mg/m2 and cyclophosphamide 500 mg/m2 could be administered safely every 10 days, allowing a projected dose-intensity of 52.5 mg/m2/wk and 350 mg/m2/wk, respectively.


2016 ◽  
Vol 23 (3) ◽  
pp. 164 ◽  
Author(s):  
S. Lupichuk ◽  
D. Tilley ◽  
X. Kostaras ◽  
A.A. Joy

Purpose We compared the efficacy, toxicity, and use of granulocyte colony–stimulating factor (G-CSF) with TAC (docetaxel–doxorubicin–cyclophosphamide) and FEC-D (5-fluorouracil–epirubicin–cyclophosphamide followed by docetaxel) in women less than 50 years of age.Methods The study included all women more than 18 years but less than 50 years of age with her2-negative, node-positive, stage II or III breast cancer diagnosed in Alberta between 2008 and 2012 who received TAC (n = 198) or FEC-D (n = 274).Results The patient groups were well-balanced, except that radiotherapy use was higher in the TAC group (91.9% vs. 79.9%, p < 0.001). At a median follow-up of 49.6 months, disease-free survival was 91.4% for TAC and 92.0% for FEC-D (p = 0.76). Overall survival (OS) was 96% with TAC and 95.3% with FEC-D (p = 0.86).The incidences of grades 3 and 4 toxicities were similar in the two groups (all p > 0.05). Overall, febrile neutropenia (FN) was reported in 11.6% of TAC patients and 15.7% of FEC-D patients (p = 0.26). However, use of G-CSF was higher in the TAC group than in the FEC-D group (96.4% vs. 71.5%, p < 0.001). Hospitalization for FN was required in 10.5% of TAC patients and 13.0% of FEC-D patients (p = 0.41). In G-CSF–supported and –unsupported patients receiving tac, FN occurred at rates of 11.1% and 33.3% respectively (p = 0.08); in patients receiving the FEC portion of FEC-D, those proportions were 2.9% and 8.1% respectively (p = 0.24); and in patients receiving docetaxel after FEC, the proportions were 4.1% and 17.6% respectively (p < 0.001).Conclusions In women less than 50 years of age receiving adjuvant TAC or FEC-D, we observed no differences in efficacy or other nonhematologic toxicities. Based on the timing and rates of FN, use of prophylactic G-CSF should be routine for the docetaxel-containing portion of treatment; however, prophylactic G-CSF could potentially be avoided during the FEC portion of FEC-D treatment.


2003 ◽  
Vol 21 (18) ◽  
pp. 3462-3468 ◽  
Author(s):  
Paola Papaldo ◽  
Massimo Lopez ◽  
Enrico Cortesi ◽  
Eugenio Cammilluzzi ◽  
Mauro Antimi ◽  
...  

Purpose: Lonidamine (LND) can enhance the activity of anthracyclines in patients with metastatic breast cancer. A multicenter, prospective, randomized trial was designed to determine whether the association of LND with high-dose epirubicin plus cyclophosphamide (EC) could improve disease-free survival (DFS) in patients with early breast cancer (BC) compared with EC alone. Granulocyte colony-stimulating factor (G-CSF) was added to maintain the EC dose-intensity. Patients and Methods: From October 1991 to April 1994, 506 patients with stage I/II BC were randomly assigned to four groups: (A) epirubicin 120 mg/m2 and cyclophosphamide 600 mg/m2 administered intravenously on day 1 every 21 days for four cycles (124 patients); (B) EC plus LND 450 mg/d administered orally (125 patients); (C) EC plus G-CSF administered subcutaneously (129 patients); (D) EC plus LND plus G-CSF (128 patients). Results: Median follow-up was 55 months. Five-year DFS rate was similar for LND (B+D groups; 69.6%) versus non-LND arms (A+C groups; 70.3%) and G-CSF (C+D groups; 67.2%) versus non–G-CSF arms (A+B groups; 72.9%). Five-year overall survival (OS) was comparable in LND (79.1%) versus non-LND arms (81.3%) and in G-CSF (80.6%) versus non–G-CSF arms (79.6%). DFS and OS distributions in LND and G-CSF arms did not change according to tumor size, node, receptor, and menopausal status. G-CSF dramatically reduced hematologic toxicity without having a significant impact on dose-intensity (98.1% v 95.5% for C+D and A+B groups, respectively). Conclusion: EC is active and well tolerated in patients with early breast cancer. The addition of LND or G-CSF does not improve DFS or OS.


Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1022
Author(s):  
Shawn C. Chafe ◽  
Nazia Riaz ◽  
Samantha Burugu ◽  
Dongxia Gao ◽  
Samuel C. Y. Leung ◽  
...  

Purpose: Granulocyte colony-stimulating factor (G-CSF) and hypoxia modulate the tumour immune microenvironment. In model systems, hypoxia-induced carbonic anhydrase IX (CAIX) has been associated with G-CSF and immune responses, including M2 polarization of macrophages. We investigated whether these associations exist in human breast cancer specimens, their relation to breast cancer subtypes, and clinical outcome. Methods: Using validated protocols and prespecified scoring methodology, G-CSF expression on carcinoma cells and CD163 expression on tumour-associated macrophages were assayed by immunohistochemistry and applied to a tissue microarray series of 2960 primary excision specimens linked to clinicopathologic, biomarker, and outcome data. Results: G-CSFhigh expression showed a significant positive association with ER negativity, HER2 positivity, presence of CD163+ M2 macrophages, and CAIX expression. In univariate analysis, G-CSFhigh phenotype was associated with improved survival in non-luminal cases, although the CAIX+ subset had a significantly adverse prognosis. A significant positive association was observed between immune checkpoint biomarkers on tumour-infiltrating lymphocytes and both G-CSF- and CAIX-expressing carcinoma cells. Immune checkpoint biomarkers correlated significantly with favourable prognosis in G-CSFhigh/non-luminal cases independent of standard clinicopathological features. Conclusions: The prognostic associations linking G-CSF to immune biomarkers and CAIX strongly support their immunomodulatory roles in the tumour microenvironment.


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