Dose-Dense Anthracycline-Based Chemotherapy for Node-Positive Breast Cancer

2002 ◽  
Vol 20 (17) ◽  
pp. 3637-3643 ◽  
Author(s):  
Georgiana K. Ellis ◽  
Robert B. Livingston ◽  
Julie R. Gralow ◽  
Stephanie J. Green ◽  
Tove Thompson
Keyword(s):  
Breast Cancer ◽  
Dose Intensity ◽  
Free Survival ◽  
Node Positive ◽  
Hand Foot Syndrome ◽  
Continuous Dose ◽  
Standard Doxorubicin ◽  
Her 2 ◽  
Dose Dense ◽  
Theoretical Considerations

PURPOSE: Theoretical considerations and clinical experience suggest that dose-dense chemotherapy may be superior to other approaches using the same drugs. We studied a dose-dense combination of doxorubicin and cyclophosphamide, with or without fluorouracil, as adjuvant therapy. PATIENTS AND METHODS: Patients with resected breast cancer were treated if they were node-positive and estrogen receptor–negative, positive for overexpression of Her-2-neu, or had four or more involved nodes. Doxorubicin was given weekly to a total dose of 480 mg/m2. Cyclophosphamide 60 mg/m2 was given daily by mouth during the period of doxorubicin treatment. The first 30 patients received fluorouracil at 300 mg/m2/wk intravenously concurrently with doxorubicin administration. In the last 22, it was omitted because of symptomatic hand-foot syndrome in the majority of patients. Filgrastim (granulocyte colony-stimulating factor [G-CSF]) was administered during chemotherapy every day except the day of intravenous administration and continued until 1 week after the completion of the chemotherapy. RESULTS: Between October 20, 1992, and June 10, 1997, we enrolled 52 patients. The mean delivered dose-intensity for doxorubicin was 18.6 mg/m2/wk. Hospitalization was required in 6% of patients for reversible febrile neutropenia. There were no acute treatment-related deaths, but one patient subsequently died of acute leukemia with a characteristic translocation for anthracycline-related exposure. At 5 years, the event-free survival was 86% for all patients (95% confidence interval, 75% to 95%). CONCLUSION: Continuous dose-dense chemotherapy with G-CSF support produced encouraging results, which seem to be superior to those expected with “standard” doxorubicin and cyclophosphamide chemotherapy. It deserves a test in the form of a randomized trial where this approach to anthracycline-based treatment is compared with intermittent administration.

Limited impact of tamoxifen following dose-intensive L-FAC multimodality therapy of breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10741-10741
Author(s):  
K. W. Jabboury ◽  
A. Wong ◽  
K. Sexton ◽  
L. Rogers ◽  
K. King ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Histological Grade ◽  
Dose Intensity ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Who Grade ◽  
Free Survival ◽  
Hand Foot Syndrome ◽  
The Impact ◽  
Grade Iii

10741 Background: Front-line dose-intensive L-FAC has demonstrated a favorable 5-year relapse free survival pattern (ASCO 2004 #739). Tamoxifen was given for 5 years to ER+ patients after L-FAC completion. We evaluated the impact of adding tamoxifen to L-FAC. By design, this pilot study excluded low-risk patients not candidates for chemotherapy. Methods: 109 breast cancer patients were enrolled (4 excluded due to treatment violations) from 6/1989 to 1/2003: 20 Stage I (S), 52 S-II, 22 S-III, for a total of 94 patients. 11 S-IV patients were excluded from survival analysis. Adverse tumor presentations included: ER- 49, PgR- 60, P53+ 24, non-diploid 39, histological grade III 37, CerbB2+ 33. L-FAC included 72 hour (h) iv infusion 400mg/m2/day (d) 5-fluorouracil (F) modulated by iv bolus 200mg/m2/d X3 leucovorin (L), concomitantly with 24h iv d1 600–1000mg/m2 cyclophosphamide (C), 48h iv d2 + d3 60mg/m2 doxorubicin (A). S-I and S-II were given 6 courses and 8 for S-III. Increasing A + C dose level and/or shortening treatment intervals < 3 weeks with growth factors provided intensification. 40 patients received tamoxifen. Results: At a median follow-up of 74 months (range 9–214), 73 (78%) are alive (1 with relapse). Relapse free survival was: S-I 95%, S-II 81%, S-III 78%. At average course intervals of 18 days, dose intensity A/C mg/m2/wk was 24.2 / 335.4 with evidence of WHO grade III/IV stomatitis in 43%, neutropenia 59%, cumulative thrombocytopenia 50%, hand-foot syndrome 32% of patients. Aside from delayed relapse associated with tamoxifen, relapse-free survival >82 months was similar with and without tamoxifen. No relapse was observed after >53 months in ER- tumors despite showing higher frequency of adverse tumor risk factors. Conclusion: The impact of adding tamoxifen appears quite limited in a patient population with adverse tumor presentation treated with dose-intensive L-FAC. No significant financial relationships to disclose.

scholarly journals Dose-Dense Epirubicin and Cyclophosphamide Followed by Docetaxel as Adjuvant Chemotherapy in Node-Positive Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Hamid Reza Mirzaei ◽  
Parisa Sabet Rasekh ◽  
Fatemeh Nasrollahi ◽  
Parto Sabet Rasekh ◽  
Zahra Akbari Tirabad ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Febrile Neutropenia ◽  
Optimal Dose ◽  
Axillary Lymph ◽  
Node Positive ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Dose Dense ◽  
Positive Breast Cancer

Background. Adding taxanes to anthracycline-based adjuvant chemotherapy has shown significant improvement particularly in node-positive patients, but optimal dose and schedule remain undetermined.Objectives. This study aimed to assess the feasibility of dose-dense epirubicin and cyclophosphamide followed by docetaxel in node-positive breast cancer.Methods. All Patients first received 4 cycles of epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) at 2-week interval then followed by docetaxel (100 mg/m2) at 2-week interval for 4 cycles, with daily Pegfilgrastim (G-CSF) that was administered in all patients on days 3–10 after each cycle of epirubicin and cyclophosphamide infusion.Results. Fifty-eight patients with axillary lymph node-positive breast cancer were enrolled in the study, of whom 42 (72.4%) completed the regimen. There were two toxicity-related deaths, one patient due to grade 4 febrile neutropenia and the other due to congestive heart failure. Grade 3/4 neutropenia and febrile neutropenia were 13.8% and 5.1%. The most common grade 3/4 nonhematological complications were as follows: skin-nail disorders (48.3%), hand-foot syndrome (34.4%), paresthesia (38%), arthralgia (27.5%), and paresis (24.1%).Conclusions. Dose-dense epirubicin and cyclophosphamide followed by docetaxel with G-CSF support are not feasible, and it is not recommended for further investigation.

A phase III adjuvant trial of sequenced EC + filgrastim + epoetin-alpha followed by paclitaxel compared to sequenced AC followed by paclitaxel compared to CEF in women with node-positive or high-risk node-negative breast cancer (NCIC CTG MA.21)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 550-550 ◽  
Author(s):  
M. J. Burnell ◽  
M. N. Levine ◽  
J. A. Chapman ◽  
V. Bramwell ◽  
T. Vandenberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Phase Iii ◽  
Free Survival ◽  
Node Negative ◽  
Node Positive ◽  
Node Negative Breast Cancer ◽  
Dose Dense

550 Background: CEF and AC followed by paclitaxel (AC/T) are commonly used adjuvant regimens in women with early breast cancer. In a trial conducted by the EORTC, NCIC CTG, and SAKK three months of dose-dense EC was equivalent to six months of CEF in women with locally advanced breast cancer. We hypothesized that three months of a taxane following dose-dense EC would be superior to CEF alone or AC/T. The results of a planned interim analysis were presented in San Antonio 2006 (Abstract #53). We now present more detailed results on efficacy and toxicity. Methods: Women 60 years of age or younger, with axillary node positive or high risk node negative breast cancer were randomized to CEF, EC/T or AC/T for six months. Results: Between December 2000 and April 2005, 2104 patients were enrolled. The median follow-up is 30.4 months. Hazard ratios for recurrence are: AC/T vs. CEF, 1.49 (95% CI, 1.12–1.99), p=0.005; AC/T vs. EC/T, 1.68 (95% CI, 1.25–2.27), p=0.0006; and EC/T vs. CEF, 0.89 (95% CI, 0.64–1.22), p=0.46. Three year recurrence-free survival rates for CEF, EC/T, and AC/T are 90.1, 89.5 and 85.0%, respectively. There was no significant interaction between ER status and treatment. Multivariate analysis of predictive factors will be presented. The numbers of deaths are 50 (CEF), 47 (EC/T) and 65 (AC/T). There was more toxicity in CEF and EC/T compared to AC/T. Conclusion: AC/T given every three weeks, although less toxic is significantly inferior to CEF or EC/T in terms of relapse-free survival. It is too early to detect any difference between CEF and dose-dense EC/T. Our results indicate that there is still room to explore anthracycline and taxane adjuvant chemotherapy regimens. Supported by: NCI Canada and Canadian Cancer Society, Pfizer, Bristol-Myers Squibb, Amgen, Janssen Ortho, Ortho Biotech, and NCI US. [Table: see text] No significant financial relationships to disclose.

Epirubicin Plus Cyclophosphamide Followed by Docetaxel Versus Epirubicin Plus Docetaxel Followed by Capecitabine As Adjuvant Therapy for Node-Positive Early Breast Cancer: Results From the GEICAM/2003-10 Study

2015 ◽  
Vol 33 (32) ◽  
pp. 3788-3795 ◽  
Author(s):  
Miguel Martín ◽  
Amparo Ruiz Simón ◽  
Manuel Ruiz Borrego ◽  
Nuria Ribelles ◽  
Álvaro Rodríguez-Lescure ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Disease Free Survival ◽  
Metastatic Breast ◽  
Invasive Disease ◽  
Hazard Ratio ◽  
Free Survival ◽  
Node Positive ◽  
Hand Foot Syndrome ◽  
Grade 3 ◽  
Disease Free

Purpose Capecitabine is an active drug in metastatic breast cancer (BC). GEICAM/2003-10 is an adjuvant trial to investigate the integration of capecitabine into a regimen of epirubicin and docetaxel for node-positive early BC. Patients and Methods Patients with operable node-positive BC (T1-3/N1-3) were eligible. After surgery, 1,384 patients were randomly assigned to receive epirubicin plus cyclophosphamide (EC; 90 and 600 mg/m2, respectively, × four cycles), followed by docetaxel (100 mg/m2 × four cycles; EC-T) or epirubicin plus docetaxel (ET; 90 and 75 mg/m2, respectively, × four cycles), followed by capecitabine (1,250 mg/m2 twice a day on days 1 to 14, × four cycles; ET-X); all regimens were given every 3 weeks. The primary end point was invasive disease-free survival. Secondary end points included safety (with an alopecia-specific study) and overall survival (OS). Results After a median follow-up of 6.6 years and 297 events, 86% of patients who received EC-T and 82% of those who received ET-X were invasive disease free at 5 years (hazard ratio, 1.30; 95% CI, 1.03 to 1.64; log-rank P = .03). The OS difference between arms was not statistically significant (hazard ratio, 1.13; 95% CI, 0.82 to 1.55; log-rank P = .46). The most frequent grade 3 to 4 adverse events in the EC-T versus ET-X arms were neutropenia (19% v 10%), with 7% febrile neutropenia across arms; fatigue (13% v 11%); diarrhea (3% v 11%); hand-foot syndrome (2% v 20%); mucositis (6% v 5%); vomiting (both, 5%); and myalgia (4.5% v 1%). Incomplete scalp hair recovery was more frequent in the EC-T than ET-X arm (30% v 14%), and patients who received EC-T wore wigs significantly longer than those who received ET-X (8.35 v 6.03 months). Conclusion Invasive disease-free survival, but not OS, was significantly superior for patients with node-positive early BC who received the adjuvant standard schedule EC-T than for those who received the experimental ET-X regimen. Toxicity profiles differed substantially across arms.

scholarly journals Composite risk and benefit from adjuvant dose-dense chemotherapy in hormone receptor-positive breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Fabio Puglisi ◽  
Lorenzo Gerratana ◽  
Matteo Lambertini ◽  
Marcello Ceppi ◽  
Luca Boni ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Effect ◽  
Hormone Receptor ◽  
Recurrence Risk ◽  
Receptor Expression ◽  
Phase Iii ◽  
Composite Measure ◽  
Node Positive ◽  
Hormone Receptor Positive ◽  
Dose Dense

AbstractThe GIM2 phase III trial demonstrated the benefit of dose-dense chemotherapy in node-positive early breast cancer (eBC). To better define the dose-dense effect in the hormone receptor-positive subgroup, we evaluated its benefit through a composite measure of recurrence risk. We conducted an ancillary analysis of the GIM2 trial evaluating the absolute treatment effect through a composite measure of recurrence risk (CPRS) in patients with hormone receptor-positive HER2-negative eBC. CPRS was estimated through Cox proportional hazards models applied to the different clinicopathological features. The treatment effect was compared to the values of CPRS by using the Sub-population Treatment Effect Pattern Plot (STEPP) process. The Disease-Free Survival (DFS)-oriented STEPP analysis showed distinct patterns of relative treatment effect with respect to CPRS. Overall, 5-year DFS differed across CPRS quartiles ranging from 95.2 to 66.4%. Each CPRS quartile was characterized by a different patients’ composition, especially for age, lymph node involvement, tumor size, estrogen and progesterone receptor expression, and Ki-67. A number needed to treat of 154 and 6 was associated with the lowest and the highest CPRS quartile, respectively. Dose-dense adjuvant chemotherapy showed a consistent benefit in node-positive eBC patients with hormone receptor-positive HER2-negative disease, but its effect varied according to CPRS.

scholarly journals Risk factors for pegylated liposomal doxorubicin-induced moderate to severe hand-foot syndrome in breast cancer patients: assessment of baseline clinical parameters

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guohua Liang ◽  
Wenjie Ma ◽  
Yanfang Zhao ◽  
Eryu Liu ◽  
Xiaoyu Shan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Prediction Model ◽  
Cancer Patients ◽  
Blood Circulation ◽  
Pegylated Liposomal Doxorubicin ◽  
Dose Intensity ◽  
Breast Cancer Patients ◽  
Hand Foot Syndrome ◽  
Peripheral Blood Circulation

Abstract Background Hand-foot syndrome (HFS) is a side effect of skin related to pegylated liposomal doxorubicin (PLD) application. Moderate to severe hand-foot syndrome (MSHFS) might have a serious impact on patients’ quality of life and treatment. However, information on risk factors for the development of MSHFS is still limited. To analyze the risk factors for PLD-induced MSHFS in breast cancer patients and constructed a logistic regression prediction model. Methods We conducted a retrospective analysis of breast cancer patients who were treated with a PLD regimen in the Tumor Hospital of Harbin Medical University from January 2017 to August 2019. A total of 26 factors were collected from electronic medical records. Patients were divided into MSHFS (HFS > grade 1) and NMHFS (HFS ≤ grade 1) groups according to the NCI classification. Statistical analysis of these factors and the construction of a logistic regression prediction model based on risk factors. Results A total of 44.7% (206/461) of patients developed MSHFS. The BMI, dose intensity, and baseline Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) levels in the MSHFS group, as well as good peripheral blood circulation, excessive sweat excretion, history of gallstones, and tumour- and HER2-positive percentages, were all higher than those in the NMHFS group (P < 0.05). The model for predicting the occurrence of MSHFS was P = 1/1 + exp. (11.138–0.110*BMI-0.234*dose intensity-0.018*baseline ALT+ 0.025*baseline AST-1.225*gallstone history-0.681* peripheral blood circulation-1.073*sweat excretion-0.364*with or without tumor-0.680*HER-2). The accuracy of the model was 72.5%, AUC = 0.791, and Hosmer-Lemeshow fit test P = 0.114 > 0.05. Conclusions Nearly half of the patients developed MSHFS. The constructed prediction model may be valuable for predicting the occurrence of MSHFS in patients.

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