Cyclophosphamide In Early Breast Cancer Research Articles

High Serum Estradiol Reduces Acute Hepatotoxicity Risk Induced by Epirubicin Plus Cyclophosphamide Chemotherapy in Premenopausal Women with Breast Cancer.

Aim: We evaluated whether acute drug-induced liver injury (DILI) caused by adjuvant chemotherapy with epirubicin plus cyclophosphamide for early breast cancer was associated with estradiol (E2), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Methods: Reproductive hormone test results of breast cancer patients were collected in the first chemotherapy cycle. E2, LH, and FSH levels were loge-transformed to normally distributed variables and were assessed using Student’s t-test to determine significant differences between the case and control groups. Hormone levels were classified according to the interquartile range and analyzed by logistic regression to determine their association with DILI caused by chemotherapy. Results: Among the 915 enrolled patients (DILI group: 204; control group: 711), menopausal status, along with serum E2, LH, and FSH levels, did not substantially differ between case and control groups. However, in the premenopause subgroup (n = 483), we found a significant difference in the E2 level between the case and control groups (p = 0.001). After adjusting for age and body mass index, premenopausal patients with 152–2,813 pg/mL E2 showed a lower risk of chemotherapy-induced DILI than patients with ≤20 pg/mL E2 (odds ratio: 0.394; 95% confidence interval: 0.207–0.748). The linear trend χ2 test revealed that E2 levels in premenopausal patients with breast cancer were inversely associated with the development of DILI. Conclusion: High serum E2 levels are associated with a reduced DILI risk in premenopausal patients with breast cancer undergoing epirubicin plus cyclophosphamide adjuvant chemotherapy.

Four versus six cycles of docetaxel and cyclophosphamide in early breast cancer.

e12047 Background: ABC trials established the use of non-anthracycline containing regimen, docetaxel and cyclophosphamide (TC) as adjuvant therapy in early breast cancer. In clinical practice, TC is commonly used in Stage I Triple Negative (TN) and Stage I,II Hormone positive breast cancer. However, no specific recommendations exist in literature, regarding the number of cycles that can be used. i.e. TC4 vs TC6. Our aim, was to determine if TC4 is non-inferior to TC6 when used as adjuvant therapy in early breast cancer. Methods: We retrospectively reviewed 143 patients who were diagnosed with early breast cancer, between 2007 to 2017, at our institution who had received either TC4 or TC6 as adjuvant therapy. The number of cycles the patients received were based on provider preference. The two groups (TC4, TC6) were compared in regard to stage of cancer at diagnosis based on AJCC 7th edition-stratified by TNM staging for hormone positive and T staging only for TN, grade of adverse events, recurrence and death from breast cancer. Median follow up was 5 years. Results: Out of the 143, 102(71.3%) received TC4 and 41(28.7%) received TC6. Among the hormone positive, 42 were stage I and out of which 32(76.2%) received TC4 and 10(23.8%) received TC6 and there were 24 stage II patients, out of which 17(70.8%) received TC4 and 7(29.2%) received TC6. Among the TN group, there were 64 who were T1, out of which 45(70.3%) received TC4 and 19(29.7%) received TC6, while there were 12 T2 patients, out of which 7(58.3%) received TC4 and 5(41.7%) received TC6. Recurrence of breast cancer was seen in 5(4.9%) in TC4 and 3(7.3%) in TC6, p=0.569. Death due to breast cancer was seen in 2(1.9%) in TC4 and 1(2.4%) in TC6, p=0.856. Adverse events were seen in 86(84.3%) in TC4 and 39(95.1%) in TC6,p=0.078. Adverse events of Grade 3 or higher were seen in 10(9.8%) in TC4 and 11(26.8%) in TC6, p=0.09. Conclusions: In this limited series, TC4 appears to be equally effective to TC6, with fewer adverse events of any grade and lower incidence of Grade 3 or higher side effects which was statistically significant. Although the proportion of patients who received TC 4 were higher in our series, the percentage of patients who received TC6 was higher in stage II for hormone positive and T2 for TN when compared to Stage 1 and T1 respectively. We also found a higher percentage of recurrence and death due to breast cancer in TC6 which was not statistically significant and this likely a reflection of the fact that as mentioned above patient with a higher stage at diagnosis tended to receive 6 cycles as compared to 4 cycles and therefore had a higher chance of recurrence in the future.

Induced Myelosuppression and Recommendation for Monitoring of Absolute Neutrophil Counts in Patients Treated with Epirubicin and Cyclophosphamide in Early Breast Cancer: Results from a Phase 2a Collaborative Trial of the AGO-B and CESAR Study Groups

IntroductionDespite much progress in the treatment of patients with malignant disorders, severe neutropenia and infections are frequent adverse events associated with standard chemotherapy regimens.Due to the low frequency of neutrophil monitoring in most clinical studies, limited insights exist about the time of the nadir, the lowest absolute neutrophil counts (ANCs), and the adequate timing of complete blood counts (CBCs) in clinical practice.ObjectiveTo analyze the trajectory of ANCs in a patient population undergoing anthracycline and cyclophosphamide treatment with the aim of producing a recommendation for the optimal time to monitor the ANCs.MethodsThe MyeloConcept Study is a randomized, double-blind, placebo-controlled, multi-centre phase 2a study, in which patients received adjuvant or neoadjuvant chemotherapy for the treatment of breast cancer. Patients were either randomized into a placebo group or an imidazolyl ethanamide pentandioic acid (IEPA, Myelo001) treatment group. The study was conducted at 23 sites in Germany between March 2016 and November 2017 (NCT02692742).This abstract reports on the placebo group of 65 patients who received background treatment with epirubicin (E) 90 mg/m2 BSA (body surface area) + cyclophosphamide (C) 600 mg/m2 BSA q21d. Patients' CBCs were measured in a central and/or local laboratory at least 9 times (on average every three days), throughout the first chemotherapy (CTX) cycle with an increased frequency when ANC decreased < 1.0 × 109 cells/L. Linear interpolation was used to obtain a continuous ANC time curve. The first occurrence and presence of grade 4 neutropenia among subjects who developed a grade 4 neutropenia were assessed on each possible monitoring day. The participating study sites provided data in the form of a questionnaire to assess ‘real-life’ ANC monitoring practice.ResultsThe mean age of the 65 female breast cancer patients was 55.7 years (SD 10.66; median 57.0), ECOG was grade 0 in > 95% of patients (Table 1). The mean time after CTX start to the ANC nadir was 13.8 days (SD 1.31; median 14.0). ANC CTCAE severity grades 3 and 4 were reached in 65 (100%) and 53 (81.5%) subjects, respectively, in the first CTX cycle (Table 2). The mean duration of grade 3 and 4 neutropenia was 7.81 days (SD 2.46; median 7.77) and 5.57 days (SD 2.48; median 5.44), respectively.Among subjects who developed a grade 4 neutropenia in this study population, the onset of grade 4 neutropenia occurred between day 10 and day 15, and most prominently on days 11 and 12 (32% and 25% of subjects, respectively (Table 3)). The greatest presence of grade 4 neutropenia (i.e. new onset or already existent neutropenia) occurred on days 13, 14 and 15 (79, 85 and 89% respectively).Based on a questionnaire of the real-life practices of the 23 participating sites, 83% (1 site gave no answer (n.a.)) evaluated CBCs at the beginning of the first cycle of CTX and during the cycle once (26%), twice (48%) or three times (9%), whereas 17% of sites did not monitor CBCs. Blood counts were assessed most frequently on days 7, 8 or 15 and monitoring was commonly (65%, 2 sites n.a.) increased once the neutrophil count fell below a certain ANC threshold, mainly below 0.5 × 109 cells/L.ConclusionsWith all subjects experiencing neutropenia grade ≥ 3 during the first CTX cycle, severe ANC toxicities undergoing q21d anthracycline and cyclophosphamide (EC) treatment were more frequently observed in this study than previously reported (Smith et al., 2006). This finding may be due to the considerably higher frequency ANC monitoring compared to prior clinical studies.In contrast to the existing ‘real-life’ practice reported, in-cycle ANC monitoring may be most informative if measured on day 11 or day 12 to assess the first occurrence (incidence) and on days 13 to 15 for the presence of grade 4 neutropenia (prevalence). A reliable and early detection system for grade 4 neutropenia offers an opportunity for the instigation of preventative measures to mitigate the infection risk for patients. DisclosuresPleimes:Bayer: Consultancy, Equity Ownership; Myelo Therapeutics: Employment, Equity Ownership. Möbus:Teva: Consultancy; Roche: Consultancy, Speakers Bureau; AstraZeneca: Speakers Bureau; Celgene: Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Myelo Therapeutics: Other: Chair of the Steering Committee of the MyeloConcept Study. Mayer:MSD: Speakers Bureau; Lily: Other: Medical Advisory Board; Myelo Therapeutics: Other: Member of the Steering Committee and Principle Investigator of MyeloConcept Study; BMS: Speakers Bureau; Incyte: Speakers Bureau. Schmidt:Janssen: Honoraria; Sividon: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Pierre-Fabre: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; Myriad Genetics: Consultancy, Honoraria; Myelo Therapeutics: Other: Member of the Steering Committee of MyeloConcept Study; Eisai: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Astra Zeneca: Consultancy, Honoraria. Asang:Myelo Therapeutics GmbH: Employment. Flunkert:Myelo Therapeutics GmbH: Consultancy, Other: Kathrin Flunkert is a salaried employee of M.A.R.C.O. GmbH & Co. KG. M.A.R.C.O. GmbH & Co. KG. had a master service agreement and received payments by Myelo Therapeutics GmbH to conduct the statistical analysis for Myelo Therapeutics. . Mikus:Myelo Therapeutics: Consultancy, Other: Member of the Data Safety Monitoring Board.

Adjuvant Capecitabine in Combination With Docetaxel, Epirubicin, and Cyclophosphamide for Early Breast Cancer

Capecitabine is not considered a standard agent in the adjuvant treatment of early breast cancer. The results of this study suggest that addition of adjuvant capecitabine to a regimen that contains docetaxel, epirubicin, and cyclophosphamide improves survival outcomes of patients with triple-negative breast cancer (TNBC). To investigate the effect of capecitabine on long-term survival outcomes of patients with early breast cancer, particularly in subgroups defined by cancer estrogen receptor (ER) and progesterone receptor (PR) content, and HER2 content (human epidermal growth factor receptor 2). This is an exploratory analysis of the multicenter FinXX randomized clinical trial that accrued 1500 women in Finland and Sweden between January 27, 2004, and May 29, 2007. About half received 3 cycles of docetaxel followed by 3 cycles of cyclophosphamide, epirubicin, and fluorouracil (T+CEF), while the other half received 3 cycles of docetaxel plus capecitabine followed by 3 cycles of cyclophosphamide, epirubicin, and capecitabine (TX+CEX). Data analysis took place between January 27, 2004, and December 31, 2015. Recurrence-free survival (RFS). Following random allocation, 747 women received T+CEF, and 753 women received TX+CEX. Five patients were excluded from the intention-to-treat population (3 had overt distant metastases at the time of randomization; 2 withdrew consent). The median age of the remaining 1495 patients was 53 years at the time of study entry; 157 (11%) had axillary node-negative disease; 1142 (76%) had ER-positive cancer; and 282 (19%) had HER2-positive cancer. The median follow-up time after random allocation was 10.3 years. There was no significant difference in RFS or overall survival between the groups (hazard ratio [HR], 0.88; 95% CI, 0.71-1.08; P = .23; and HR, 0.84, 95% CI, 0.66-1.07; P = .15; respectively). Breast cancer-specific survival tended to favor the capecitabine group (HR, 0.79; 95% CI, 0.60-1.04; P = .10). When RFS and survival of the patients were compared within the subgroups defined by cancer steroid hormone receptor status (ER and/or PR positive vs ER and PR negative) and HER2 status (positive vs negative), TX+CEX was more effective than T+CEF in the subset of patients with TNBC (HR, 0.53; 95% CI, 0.31-0.92; P = .02; and HR, 0.55, 95% CI, 0.31-0.96; P = .03; respectively). Capecitabine administration with docetaxel, epirubicin, and cyclophosphamide did not prolong RFS or survival compared with a regimen that contained only standard agents. Patients with TNBC had favorable survival outcomes when treated with the capecitabine-containing regimen in an exploratory subgroup analysis. clinicaltrials.gov Identifier: NCT00114816.

High incidence of febrile neutropenia seen following adjuvant chemotherapy with docetaxel plus cyclophosphamide for early breast cancer

A LETTER IN RESPONSE TO: Lakhanpal R, Stuart-Harris R, Chan A et al. Docetaxel and cyclophosphamide as adjuvant chemotherapy for early breast cancer: primary prophylaxis with G-CSF is required. Breast Cancer Manage. 2(5), 367–374 (2013).

Hematologic toxicity with adjuvant docetaxel and cyclophosphamide in early breast cancer.

e11081 Background: After the results of docetaxel and cyclophosphamide (TC) superiority over doxorubicin and cyclophosphamide (AC) scheme, TC has been adopted at the A. C. Camargo Cancer Hospital as an option for adjuvant chemotherapy to early-breast cancer patients. However we have noticed a high rate of febrile neutropenia with this schedule. Methods: We conducted a retropective analysis of all patients with early breast cancer submitted to adjuvant chemotherapy with docetaxel 75 mg/m2 plus cyclophosphide 600 mg/m2, between January 2008 and July 2009, at A. C. Camargo Hospital in São Paulo-SP, Brazil. Primary end-point was to evaluate the rate of febrile neutropenia. Results: We have treated 30 women with TC. Median age was 55.7 years (33 to 76 years old). With regards to histologic caracteristics 58.6% were T1, 37.9% were T2, with a median tumor size of 16 mm; 6.9% had macroscopic positive axilar node; 65.5% patients were hormone receptor positive, 13.8% were HER2/neu positive. There was a total of 118 cycles of TC and we had 41.9% (n = 12) of patients with grade 3 or 4 neutropenia, and 31% (n = 9) needed hospitalization for febrile neutropenia (FN). Two patients initated TC with primary prophylaxis with growth factor. When we analysed only the first cycle, we found that 20.9% (n = 6) of patients had FN. After the first event, the use of secundary prophylaxis was initiated in all patients (n = 7) and there was still two further hospitalization for NF. One of them had dose reduction. Mean time of filgrastim 300 mcg/d administration was 5 days. We had no death related to FN. Ninety-three percent of all patients completed the treatment programmed. Conclusions: We have found a higher rate of FN with hospitalization (31%), in contrast with the hematologic toxicity reported preveously by US Oncology Group. The use of growth factor was able to prevent most of further hospitalization and mantain dose-intensity. G-CSF prophylaxis should be used in patients receiving adjuvant TC. No significant financial relationships to disclose.

Risk of venous thromboembolism in patients receiving adjuvant chemotherapy with 5‐fluorouracil, epirubicin and cyclophosphamide for early breast cancer

AbstractAim: Previous studies have shown that adjuvant chemotherapy in early breast cancer (EBC) may increase the risk of venous thromboembolism (VTE). Clinical experience suggests the combination of 5‐fluorouracil, epirubicin and cyclophosphamide (FEC) may be associated with a higher frequency of VTE than other regimens. This study aims to investigate the use of adjuvant FEC compared with other adjuvant regimens in the development of VTE in patients with EBC.Methods: A retrospective audit was conducted examining all eligible patients who received adjuvant chemotherapy for EBC in the Australian Capital Territory from 1 January 2005 to 30 June 2007. Data were collected from patients' notes, including risk factors for VTE, tumor pathology, chemotherapy details and incidence of VTE. Comparisons using χ2 tests and independent samples t‐tests were made between patients who received FEC and those who received another regimen. Multivariate logistic regression was used to investigate prognostic factors for the development of VTE.Results: A total of 325 patients were included in the study, of whom 176 received FEC and 149 received other adjuvant chemotherapy regimens. The incidence of VTE in patients who received FEC was 47/176 (27%), which was significantly higher than for patients who received other regimens (7/149, 5%, P &lt; 0.001). FEC was the only significant prognostic factor for the development of VTE (OR 7.9, 95% CI 3.3–19.2, P &lt; 0.001).Conclusion: The use of adjuvant FEC chemotherapy is associated with an increased incidence of VTE in patients with EBC compared with other commonly used chemotherapy regimens.

Adjuvant fluorouracil, epirubicin and cyclophosphamide in early breast cancer: Is it cost-effective?

Adjuvant chemotherapy (ACT) in breast cancer exposes patients to morbidity, but improves survival. The FEC (fluorouracil, epirubicin, cyclophosphamide) regimen has taken over the prior role of CMF (cyclophosphamide, methotrexate, fluorouracil). In this model, efficacy, tolerability and quality of life (QoL) data from the literature were incorporated with Norwegian practice and cost data in a cost-effectiveness approach. The FEC efficacy was calculated 3–7% superior CMF. There was no difference in quality of life. An 80–100% dose intensity range was employed, one Euro (€ 1) was calculated NOK 8.78 and a 3% discount rate was used. The total cost of FEC employing the friction cost method on production loss, including amount spent on drugs, administration and travelling ranged between € 3 278–3 850 (human capital approach € 12 143–12 715). Money spent on drugs alone constituted 15–48%, depending on method chosen. A cost-effectiveness analysis revealed a cost per life year (LY) saved replacing FEC by CMF of € 3 575–15 125. Adjuvant FEC is cost effective in Norway.

Immediate toxicity among Chinese patients undergoing adjuvant doxorubicin and cyclophosphamide for early breast cancer- a single institute experience with comparison to historic Western series

Immediate toxicity among Chinese patients undergoing adjuvant doxorubicin and cyclophosphamide for early breast cancer- a single institute experience with comparison to historic Western series

Acute toxicity of adjuvant doxorubicin and cyclophosphamide for early breast cancer – a retrospective review of Chinese patients and comparison with an historic Western series

A cohort of 85 Chinese breast cancer patients who received adjuvant chemotherapy with doxorubicin and cyclophosphamide was found to have a significantly higher incidence of grade 3 ( n=44, 52%) and grade 4 ( n=21, 25%) neutropenia when compared with an historic Western cohort. Also noted was a higher incidence of hepatotoxicity ( n=8, 9%). When compared to Caucasian patients, the higher myelotoxicity in our patients may be related to ethnic variation in susceptibility to chemotherapy-related toxicity, lower body mass index with higher percentage of body fat composition, and the popular practice of concurrent alternative medicine during chemotherapy. The higher incidence of hepatoxicity was possibly associated with endemic chronic hepatitis B infection in this geographical area.