Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00

Fountzilas, George; Dafni, Urania; Gogas, Helen; Linardou, Helena; Kalofonos, Haralabos P.; Briasoulis, Evangelos; Pectasides, Dimitrios; Samantas, Epaminontas; Bafaloukos, Dimitrios; Stathopoulos, George P.; Karina, M.; Papadimitriou, C.; Skarlos, Dimosthenis; Pisanidis, Nikolaos; Papakostas, Pavlos; Markopoulos, Christos; Tzorakoeleftherakis, Evangelos; Dimitrakakis, Konstantinos; Makrantonakis, P.; Xiros, Nikolaos I.; Polichronis, A.; Varthalitis, Ioannis; Karanikiotis, Charisios; Dimopoulos, Meletios Α.

doi:10.1093/annonc/mdm539

Cited by 46 publications

(42 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, DI of the essential drugs, epirubicin and paclitaxel, was double in the sequential dose-dense arm. Safety analysis results have been previously reported [10]. In this report, we present the efficacy results of this trial.…”

Section: Introductionmentioning

confidence: 63%

Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial

Gogas

Dafni

Karina

et al. 2011

Breast Cancer Res Treat

View full text Add to dashboard Cite

To explore the impact of dose intensity (DI) in the adjuvant setting of breast cancer, a randomized phase III trial was conducted comparing postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel, and cyclophosphamide, methotrexate and fluorouracil (CMF)in high-risk breast cancer patients. From Oct 2000 to June 2005, 1,121 node-positive patients were randomized to dose-dense sequential epirubicin 110 mg/m(2) and paclitaxel (Taxol, Bristol Myers-Squibb, Princeton, NJ) 250 mg/m(2) (group A), or concurrent epirubicin 83 mg/m(2) and paclitaxel 187 mg/m(2) (group B), both followed by three cycles of "intensified" combination chemotherapy with CMF. By protocol design total cumulative dose and duration of treatment were identical in both groups. Dose intensity of epirubicin and paclitaxel was double in the dose-dense arm. Prophylactic treatment with granulocyte colony-stimulating factor was given with the dose-dense treatments. Disease-free survival (DFS) was the primary endpoint. At a median follow-up of 76 months, 253 patients (23%) had documented disease relapse (123 vs. 130 in groups A and B, respectively) and 208 deaths (101, group A and 107, group B) had been observed. The 5-year DFS rate of 74 and 74% and OS rate of 86 and 85% were observed for group A and group B, respectively. No differences were found in DFS or OS between the two treatment groups (P = 0.78 and P = 0.45 for DFS and OS, respectively). Safety analysis results showing that both regimens were well tolerated and safe have been previously published (Fountzilas et al. Ann Oncol 2008). No DFS or OS benefit from the dose-dense sequential epirubicin and paclitaxel was detected when compared to the concurrent administration of the same drugs. No additional safety issues were raised with long-term follow-up.

show abstract

Section: Introductionmentioning

confidence: 63%

Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial

Gogas

Dafni

Karina

et al. 2011

Breast Cancer Res Treat

View full text Add to dashboard Cite

show abstract

“…Group A: epirubicin (E) 110 mg/m 2 every 2 weeks for 3 cycles, followed by 3 cycles of paclitaxel (T, 250 mg/m 2 ) every 2 weeks, followed by 3 cycles of CMF (cyclophosphamide 840 mg/m 2 , methotrexate 57 mg/m 2 and 5-fluorouracil 840 mg/m 2 ) every 2 weeks (E-T-CMF) [12]. …”

Section: Methodsmentioning

confidence: 99%

“…The Hellenic Cooperative Oncology Group has employed dose-dense sequential regimens biweekly with G-CSF support from day 2 to day 10 of each chemotherapy cycle. Those regimens proved to be efficacious and safe, provided that G-CSF was also administered as primary prophylaxis [12, 13]. …”

Section: Introductionmentioning

confidence: 99%

Pegfilgrastim Administered on the Same Day with Dose-Dense Adjuvant Chemotherapy for Breast Cancer Is Associated with a Higher Incidence of Febrile Neutropenia as Compared to Conventional Growth Factor Support: Matched Case-Control Study of the Hellenic Cooperative Oncology Group

et al. 2009

View full text Add to dashboard Cite

Objective: Recombinant human granulocyte-colony-stimulating factors such as filgrastim and pegfilgrastim have been employed as primary and secondary prophylaxis against neutropenia in cancer patients receiving chemotherapy. This study was conducted to evaluate the rate of febrile neutropenia in patients with high-risk early breast cancer receiving dose-dense chemotherapy and, as primary prophylaxis, either pegfilgrastim 6 mg fixed dose on the same day as chemotherapy or filgrastim on days 2–10 of each cycle. Secondary objectives included the rate of severe neutropenia, treatment delays and dose reductions. Methods: This was a nonrandomized matched case-control study with 214 patients receiving dose-dense chemotherapy. Each group receiving supportive therapy included 107 patients (pegfilgrastim and filgrastim groups). Results: Fourteen patients (13%) in the pegfilgrastim group developed febrile neutropenia as compared to 1 patient (1%) in the filgrastim group (p = 0.001). No statistically significant differences regarding the rate of severe neutropenia, treatment delays and dose reductions were observed. Conclusion: The results demonstrate that pegfilgrastim administered as primary prophylaxis on the same day as dose-dense chemotherapy is less efficacious than filgrastim administered on days 2–10 of each chemotherapy cycle. For the particular regimens given in this retrospective matched case-control study, the current recommendation for administering pegfilgrastim at least 24 h after chemotherapy completion seems justified. However, further randomized controlled trials are needed to clarify this finding.

show abstract

“…All patients (n = 7,025) that were part of the HE 10/97 [33], HE 10/00 [34], HE 10/04 [35,36], HE 10/05 (unpublished), HE 10/08 (unpublished), HE 11/02 [37], HE 11/06 [38], and HE 11/07 [39] prospective clinical trial populationscoordinated and conducted by HeCOG-were checked for ER, PR, and HER2 status based on initial histology report; paraffin-embedded tissue blocks of all patients enrolled before 2004 or with metastatic disease were additionally assessed by central pathology review (n = 2,566). Trial eligibility criteria did not include any selection based on age of onset or family history.…”

Section: Patient Study Groupmentioning

confidence: 99%

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study

Fostira

Tsitlaidou

Papadimitriou

et al. 2012

Breast Cancer Res Treat

View full text Add to dashboard Cite

In spite the close association of the triple-negative breast cancer immunophenotype with hereditary breast cancers and the BRCA1 pathway, there is a lack of population studies that determine the frequency of BRCA1 mutations among triple-negative breast cancer patients. To address this, we have screened a large sample of 403 women diagnosed with triple-negative invasive breast cancer, independently of their age or family history, for germline BRCA1 mutations. Median age at diagnosis was 50 years (range 20-83). The overall prevalence of triple-negative cases among the initial patient group with invasive breast cancer was 8%. BRCA1 was screened by direct DNA sequencing in all patients, including all exons where a mutation was previously found in the Greek population (exons 5, 11, 12, 16, 20, 21, 22, 23, 24-77% of the BRCA1 coding region), including diagnostic PCRs to detect the three Greek founder large genomic rearrangements. Sixty-five deleterious BRCA1 mutations were identified among the 403 triple-negative breast cancer patients (16%). Median age of onset for mutation carriers was 39 years. Among a total of 106 women with early-onset triple-negative breast cancer (<40 years), 38 (36%) had a BRCA1 mutation, while 27% of women with triple-negative breast cancer diagnosed before 50 years (56/208) had a BRCA1 mutation. A mutation was found in 48% (50/105) of the triple-negative breast cancer patients with family history of breast or ovarian cancer. It is noteworthy, however, that of the 65 carriers, 15 (23%) had no reported family history of related cancers. All but one of the carriers had grade III tumors (98%). These results indicate that women with early-onset triple-negative breast cancer, and ideally all triple-negative breast cancer patients, are candidates for BRCA1 genetic testing even in the absence of a family history of breast or ovarian cancer.

show abstract

Postoperative dose-dense sequential chemotherapy with epirubicin, paclitaxel and CMF in patients with high-risk breast cancer: safety analysis of the Hellenic Cooperative Oncology Group randomized phase III trial HE 10/00

Abstract: Both regimens as used in the present study are well tolerated and safe. The rates of severe taxane-related toxic effects and thrombocytopenia, although low overall, are significantly increased with the dose-dense sequential regimen.

Cited by 46 publications

References 27 publications

Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial

Postoperative dose-dense sequential versus concomitant administration of epirubicin and paclitaxel in patients with node-positive breast cancer: 5-year results of the Hellenic Cooperative Oncology Group HE 10/00 phase III Trial

Pegfilgrastim Administered on the Same Day with Dose-Dense Adjuvant Chemotherapy for Breast Cancer Is Associated with a Higher Incidence of Febrile Neutropenia as Compared to Conventional Growth Factor Support: Matched Case-Control Study of the Hellenic Cooperative Oncology Group

Prevalence of BRCA1 mutations among 403 women with triple-negative breast cancer: implications for genetic screening selection criteria: a Hellenic Cooperative Oncology Group Study

Contact Info

Product

Resources

About