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1.
Ann Oncol ; 28(1): 103-109, 2017 01 01.
Article in English | MEDLINE | ID: mdl-28177480

ABSTRACT

Background: We present a pooled analysis of predictive and prognostic values of circulating tumour cells (CTC) and circulating endothelial cells (CEC) in two prospective trials of patients with inflammatory breast cancer (IBC) treated with neoadjuvant chemotherapy combined with neoadjuvant and adjuvant bevacizumab. Patients and methods: Nonmetastatic T4d patients were enrolled in two phase II multicentre trials, evaluating bevacizumab in combination with sequential neoadjuvant chemotherapy of four cycles of FEC followed by four cycles of docetaxel in HER2-negative tumour (BEVERLY-1) or docetaxel and trastuzumab in HER2-positive tumour (BEVERLY-2). CTC and CEC were detected in 7.5 and 4 ml of blood, respectively, with the CellSearch System. Results: From October 2008 to September 2010, 152 patients were included and 137 were evaluable for CTC and CEC. At baseline, 55 patients had detectable CTC (39%). After four cycles of chemotherapy, a dramatic drop in CTC to a rate of 9% was observed (P < 0.01). Pathological complete response (pCR) rate was 40%. No correlation was found between CTC or CEC levels and pCR rate. Median follow-up was 43 months. CTC detection (≥1 CTC/7.5 ml) at baseline was associated with shorter 3-year disease-free survival (39% versus 70% for patients without CTC, P < 0.01, HR 2.80) and shorter 3-year overall survival (OS) (P < 0.01). In multivariate analysis, independent prognostic parameters for shorter survival were absence of hormonal receptors, no pCR and CTC detection at baseline. CEC level at baseline or variations during treatment had no prognostic value. Conclusion: In this pooled analysis of two prospective trials in nonmetastatic IBC, detection rate of CTC was 39% with a strong and independent prognostic value for survival. Combination of pCR after neoadjuvant treatment with no CTC detection at baseline isolated a subgroup of IBC with excellent OS (94% 3-year OS), suggesting that CTC count could be part of IBC stratification in prospective trials.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Inflammatory Breast Neoplasms/drug therapy , Inflammatory Breast Neoplasms/pathology , Neoplastic Cells, Circulating/drug effects , Neoplastic Cells, Circulating/pathology , Adult , Aged , Bevacizumab/administration & dosage , Chemotherapy, Adjuvant , Cyclophosphamide/administration & dosage , Disease-Free Survival , Docetaxel , Epirubicin/administration & dosage , Female , Humans , Inflammatory Breast Neoplasms/blood , Inflammatory Breast Neoplasms/surgery , Middle Aged , Neoadjuvant Therapy , Prognosis , Receptor, ErbB-2/metabolism , Taxoids/administration & dosage , Trastuzumab/administration & dosage , Young Adult
2.
Ann Oncol ; 27(7): 1235-41, 2016 07.
Article in English | MEDLINE | ID: mdl-27029707

ABSTRACT

BACKGROUND: A minority of early breast cancer (EBC) patients treated with adjuvant or neoadjuvant chemotherapy have sufficient baseline vitamin D (vitD) level. This randomized phase III study assessed the safety and efficacy of a tailored, high-dose, oral vitD supplementation in restoring a normal 25-hydroxy vitD (25OHD) level in this population. PATIENTS AND METHODS: Participants received a 6-month conventional (C) vitD and calcium supplementation or a 6-month high-dose oral vitD regimen tailored on the deficiency (T) and a conventional calcium supplementation. The primary end point was the 6-month percentage of 25OHD serum level normalization. RESULTS: A total of 215 patients including 197 patients with vitD deficiency were recruited, and 195 patients were randomized (T, 100; C, 95). Compliance to the daily oral supplementation was 68.4% and 67% in the C and T arms, respectively. Discontinuous high-dose vitD compliance appeared higher in the T arm (77%). At 6 months, more patients presented with a normalized vitD level in the T arm (30% versus 12.6%; P = 0.003). Supplementation was well tolerated, and no significant difference in the treatment-related toxicity between the two arms was reported. Fifty-two patients without vitD normalization from the C arm switched to the T arm after 6 months. At 12 months, 44% of these patients achieved vitD normalization. CONCLUSION: A tailored high-dose oral vitD supplementation safely allows a higher percentage of the serum 25OHD level normalization compared with a conventional regimen in chemotherapy-treated EBC patients. As compliance to a daily oral supplementation remains poor in this setting, an adaptation of the treatment schedule is warranted. CLINICAL TRIAL NUMBER: NCT01480869.


Subject(s)
Breast Neoplasms/diet therapy , Dietary Supplements , Vitamin D Deficiency/diet therapy , Vitamin D/administration & dosage , Adult , Aged , Breast Neoplasms/blood , Breast Neoplasms/pathology , Drug-Related Side Effects and Adverse Reactions/pathology , Female , Humans , Middle Aged , Neoplasm Staging , Quality of Life , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/blood , Vitamin D Deficiency/pathology
3.
Ann Oncol ; 27(3): 474-80, 2016 Mar.
Article in English | MEDLINE | ID: mdl-26681684

ABSTRACT

BACKGROUND: We present here final clinical results of the COHORT trial and both translational sub-studies aiming at identifying patients at risk of radiation-induced subcutaneous fibrosis (RISF): (i) radiation-induced lymphocyte apoptosis (RILA) and (ii) candidates of certain single-nucleotide polymorphisms (SNPs). PATIENTS AND METHODS: Post-menopausal patients with stage I-II breast cancer (n = 150) were enrolled and assigned to either concurrent (arm A) or sequential radiotherapy (RT)-letrozole (arm B). Among them, 121 were eligible for RILA and SNP assays. Grade ≥2 RISF were the primary end point. Secondary end points were lung and heart events and carcinologic outcome. RILA was performed to predict differences in RISF between individuals. A genome-wide association study was performed to identify SNPs associated with RILA and RISF. Analyses were done by intention to treat. RESULTS: After a median follow-up of 74 months, 5 patients developed a grade ≥2 RISF. No significant difference was observed between arms A and B. Neither grade ≥2 lung nor symptomatic cardiac toxicity was observed. Median RILA value of the five patients who had grade ≥2 RISF was significantly lower compared with those who developed grade ≤1 RISF (6.9% versus 13%, P = 0.02). Two SNPs were identified as being significantly associated with RILA: rs1182531 (P = 4.2 × 10(-9)) and rs1182532 (P = 3.6 × 10(-8)); both located within the PHACTR3 gene on chromosome 20q13.33. CONCLUSIONS: With long-term follow-up, letrozole can safely be delivered concomitantly with adjuvant breast RT. Translational sub-studies showed that high RILA values were correlated with patients who did not develop RISF. REGISTERED CLINICAL TRIAL: NCT00208273.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Combined Modality Therapy/adverse effects , Nitriles/therapeutic use , Radiotherapy, Adjuvant/adverse effects , Triazoles/therapeutic use , Aged , Aged, 80 and over , Apoptosis/genetics , Female , Fibrosis/genetics , Genome-Wide Association Study , Humans , Letrozole , Middle Aged , Nuclear Proteins/genetics , Polymorphism, Single Nucleotide/genetics
4.
Ann Oncol ; 26(9): 1904-1910, 2015 Sep.
Article in English | MEDLINE | ID: mdl-26202594

ABSTRACT

BACKGROUND: Increased hepatocyte growth factor/MET signaling is associated with an aggressive phenotype and poor prognosis in triple-negative breast cancer (TNBC). We evaluated the benefit of adding onartuzumab, a monoclonal anti-MET antibody, to paclitaxel with/without bevacizumab in patients with TNBC. PATIENTS AND METHODS: Women with metastatic TNBC were randomized to receive onartuzumab plus placebo plus weekly paclitaxel (OP; n = 60) or onartuzumab plus bevacizumab plus paclitaxel (OBP; n = 63) or placebo plus bevacizumab plus paclitaxel (BP; n = 62). The primary end point was progression-free survival (PFS); additional end points included overall survival (OS), objective response rate (ORR), and safety. This trial was hypothesis generating and did not have power to detect minimum clinically meaningful differences between treatment arms. RESULTS: There was no improvement in PFS with the addition of onartuzumab to BP [hazard ratio (HR), 1.08; 95% confidence interval (CI) 0.69-1.70]; the risk of a PFS event was higher with OP than with BP (HR, 1.74; 95% CI 1.13-2.68). Most patients had MET-negative tumors (88%); PAM50 subtype analysis showed basal-like tumors in 68% of samples. ORR was higher in the bevacizumab arms (OBP: 42.2%; 95% CI 28.6-57.1; BP: 54.7%; 95% CI 41.0-68.4) compared with OP (27.5%; 95% CI 15.9-40.6). Median OS was shorter with OBP (HR, 1.36; 95% CI 0.75-2.46) and OP (HR, 1.92; 95% CI 1.03-3.59), than with BP. Peripheral edema was more frequent in the onartuzumab arms (OBP, 51.8%; OP, 58.6%) versus BP (17.7%). CONCLUSION: This study did not show a clinical benefit of the addition of onartuzumab to paclitaxel with/without bevacizumab in patients with predominantly MET-negative TNBC. CLINICALTRIALSGOV: NCT01186991.


Subject(s)
Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bevacizumab/therapeutic use , Paclitaxel/therapeutic use , Triple Negative Breast Neoplasms/drug therapy , Adult , Aged , Angiogenesis Inhibitors/adverse effects , Angiogenesis Inhibitors/therapeutic use , Antibodies, Monoclonal/adverse effects , Antineoplastic Agents, Phytogenic/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab/adverse effects , Disease-Free Survival , Female , Humans , Middle Aged , Paclitaxel/adverse effects , Placebos/therapeutic use
5.
Ann Oncol ; 25(8): 1563-70, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24827132

ABSTRACT

BACKGROUND: At 42.5 months of median follow-up, PHARE failed to show that 6 was non-inferior to 12 months of adjuvant trastuzumab. From the results of PHARE, questions remain regarding whether the magnitude of benefit derived from 1 year is sufficient to justify its systematic use for different patient subgroups. METHODS: Treatment effects were evaluated according to various tumour characteristics, and the multivariate Cox proportional hazards regression models were carried out on metastases-free survival (MFS) in the 12 months control arm. A prognostic score was defined providing the identification of patient categories with similar risks. The 6-month arm was used as a validation set in order to test for heterogeneity. This study is registered at clinicaltrials.gov, number NCT00381901. RESULTS: A total of 261 metastatic events were observed and four prognostic groups were defined: very low, low, intermediate and high risk in the 12-month arm. The corresponding 3-year MFS rates were 98.3%, 95.8%, 90.4% and 78.4% in the four prognostic groups, respectively. In the 6-month arm, the 3-year MFS rates were 98.3%, 94.2%, 85.7% and 74.8% in the four prognostic groups, respectively. CONCLUSION: In the very low-risk group, the potential absolute benefit of standard duration of trastuzumab was small enough to indicate that optimal standard treatment might be clinically questionable. On the other hand, the 3-year metastasis occurrence rates strongly support the need for a search of a more efficient treatment in the low-, intermediate- and high-risk groups.


Subject(s)
Antibodies, Monoclonal, Humanized/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Antineoplastic Agents/therapeutic use , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Chemotherapy, Adjuvant , Female , France/epidemiology , Humans , Lymphatic Metastasis , Middle Aged , Neoplasm Metastasis , Receptor, ErbB-2/metabolism , Survival Analysis , Trastuzumab , Tumor Burden
6.
Ann Oncol ; 24(12): 2999-3004, 2013 Dec.
Article in English | MEDLINE | ID: mdl-24013510

ABSTRACT

BACKGROUND: Decrease of circulating tumor cells (CTC) during treatment is an independent prognostic factor in metastatic breast cancer (MBC). We specifically evaluated the impact of CTC on brain metastasis outcome. METHODS: HER2-positive MBC with brain metastasis not previously treated with whole-brain radiotherapy received first-line combination of lapatinib and capecitabine in a phase II study. CTC were detected at baseline and day 21 (CellSearch). RESULTS: Median follow-up of the 44 analyzed patients was 21.2 months. The central nervous system objective response (CNS-OR) rate was 66%. At baseline, 20 of 41 assessable patients for CTC (49%) had ≥1 CTC (range 1-301, median 3) and 9 (22%) had ≥5 CTC. At day 21, 7 of 38 patients (18%) had ≥1 CTC (P = 0.006, versus baseline), and CTC had disappeared in 11 patients. CNS-OR rate was significantly higher in patients with no CTC at day 21 [25 of 31 (80%) versus 2 of 7 (29%), P = 0.01]. The 1-year overall survival rate was 83.9% in patients with no CTC at day 21 versus 42.9% in patients with ≥1 CTC (P = 0.02). CONCLUSIONS: This is the first report showing a correlation between CNS metastasis response, outcome and early CTC clearance under targeted treatment of HER2+ MBC. CLINICAL TRIALS NUMBER: NCT00967031.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Brain Neoplasms/drug therapy , Breast Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Adult , Aged , Brain Neoplasms/metabolism , Brain Neoplasms/mortality , Brain Neoplasms/secondary , Breast Neoplasms/metabolism , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Capecitabine , Chemoradiotherapy , Deoxycytidine/administration & dosage , Deoxycytidine/analogs & derivatives , Disease-Free Survival , Female , Fluorouracil/administration & dosage , Fluorouracil/analogs & derivatives , Humans , Kaplan-Meier Estimate , Lapatinib , Middle Aged , Neoplastic Cells, Circulating/metabolism , Prognosis , Quinazolines/administration & dosage , Treatment Outcome
7.
Target Oncol ; 8(2): 137-43, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23609057

ABSTRACT

This trial evaluated the effect of adding lapatinib to letrozole after clinical resistance to aromatase inhibitor (IA) treatment in hormone receptor-positive metastatic breast cancer. Postmenopausal women received daily letrozole plus lapatinib (1,500 mg). The primary end point was objective rate response (ORR) at week 12. Secondary objectives included time to response, duration of response, clinical benefit (CB), progression-free survival (PFS), overall survival, and safety. Twenty-four human epidermal growth factor receptor 2 (HER2)-negative patients were included with secondary resistance to IA. ORR at 12 weeks was 4 % (95 % confidence interval (CI), 0.7-20). Stable and progression diseases were reported in 25 % (95 % CI, 12-45) and 71 % (95 % CI, 51-85) of cases, respectively. At 24 weeks, the ORR increased to 8 %. CB was 21 % (95 % CI, 9-40). At a median follow-up of 27 months, median PFS was 3.4 months (95 % CI, 2.8-5.4). Grade 3 or 4 adverse events were rarely reported. No clinical cardiac toxicity was observed. Lapatinib was discontinued in two patients due to severe diarrhea. This trial was prematurely closed due to low recruitment. These preliminary results suggest that the addition of lapatinib to letrozole has a favorable safety profile and could overcome tumoral resistance to letrozole among HER2-negative tumors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/drug therapy , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Aromatase Inhibitors/administration & dosage , Aromatase Inhibitors/adverse effects , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cohort Studies , Drug Resistance, Neoplasm , ErbB Receptors/antagonists & inhibitors , Female , Humans , Lapatinib , Letrozole , Middle Aged , Neoplasm Grading , Nitriles/administration & dosage , Nitriles/adverse effects , Quinazolines/administration & dosage , Quinazolines/adverse effects , Receptor, ErbB-2/antagonists & inhibitors , Treatment Outcome , Triazoles/administration & dosage , Triazoles/adverse effects
8.
Br J Cancer ; 108(5): 1052-60, 2013 Mar 19.
Article in English | MEDLINE | ID: mdl-23422754

ABSTRACT

BACKGROUND: Combining bevacizumab with first-line chemotherapy significantly improves progression-free survival (PFS) in HER2-negative metastatic breast cancer (mBC). However, identification of patients benefitting most from bevacizumab remains elusive. The AVADO trial included an extensive optional exploratory biomarker programme. METHODS: Patients with HER2-negative mBC were randomised to receive docetaxel with placebo or bevacizumab. The primary end point was PFS. Plasma samples were analysed using a multiplex ELISA. Blood mRNA expression was assessed using quantitative PCR. Tumour tissue samples were analysed by immunohistochemistry. Single-nucleotide polymorphisms (SNPs) involved in the VEGF pathway were analysed in germline DNA. RESULTS: Samples for biomarker analysis were available from 24-54% of the 736 treated patients (depending on specimen type). The most consistent potential predictive effect was observed with plasma VEGF-A and VEGFR-2; high baseline concentrations were associated with greater treatment effect. Blood mRNA analyses suggested a greater bevacizumab effect in patients with high VEGF121. No consistent predictive effect was seen for tumour neuropilin or other candidate tumour markers by immunohistochemistry, or for any of the SNPs investigated. CONCLUSION: Plasma VEGF-A and VEGFR-2 are potential predictive markers for bevacizumab efficacy, supporting findings in gastric and pancreatic cancers. Plasma VEGF-A is being evaluated prospectively in mBC in the MERiDiAN trial.


Subject(s)
Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Biomarkers, Tumor/blood , Breast Neoplasms/drug therapy , Receptor, ErbB-2/metabolism , Taxoids/administration & dosage , Vascular Endothelial Growth Factor A/blood , Vascular Endothelial Growth Factor Receptor-2/blood , Adult , Aged , Aged, 80 and over , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Bevacizumab , Breast Neoplasms/blood , Breast Neoplasms/genetics , Breast Neoplasms/pathology , Disease-Free Survival , Docetaxel , Female , Humans , Middle Aged , Neoplasm Metastasis , Polymorphism, Single Nucleotide , Predictive Value of Tests
9.
Ann Oncol ; 23(11): 2879-2884, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22571858

ABSTRACT

BACKGROUND: To analyze the clinical and histological features of permanent alopecia following a sequential fluorouracil/epirubicin/cyclophosphamide (FEC) and docetaxel regimen for adjuvant breast cancer treatment. PATIENTS AND METHODS: Women treated for breast cancer by a sequential adjuvant FEC and docetaxel regimen who developed permanent alopecia diagnosed between 2007 and 2011 were identified from the Department of Dermatology (Saint-Eloi Hospital, Montpellier, France) and the Department of Medical Oncology (CRLC Val d'Aurelle, Montpellier, France). Data were collected regarding demographics, type of cancer, delay of onset after chemotherapy, Dermatology Life Quality Index (DLQI), clinical description of the lesions, scalp biopsies, laboratory explorations investigating steroid hormonal, iron, zinc and thyroid status, therapy and outcome. RESULTS: Twenty white Caucasian females were included. Hair loss presented with a moderate or intense androgenetic-like pattern of scalp alopecia. Biopsy specimen examinations were normal or displayed the androgenetic-like pattern. Laboratory explorations ruled out iron or zinc deficiency and thyroid disorders and confirmed hormonal menopause without hyperandrogenism. The overall mean DLQI score reflected the distressing psychological consequences in the patients' lives. No spontaneous regrowth of the scalp hair was noted. Treatment including vitamins, minoxidil, psoralen and ultraviolet A therapy and spironolactone proved to be ineffective. CONCLUSION: Permanent and severe alopecia is a newly reported complication of the FEC 100-docetaxel breast cancer regimen.


Subject(s)
Alopecia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Breast Neoplasms/drug therapy , Taxoids/adverse effects , Adult , Aged , Alopecia/drug therapy , Alopecia/therapy , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Chemotherapy, Adjuvant/adverse effects , Cyclophosphamide/adverse effects , Cyclophosphamide/therapeutic use , Docetaxel , Epirubicin/adverse effects , Epirubicin/therapeutic use , Female , Ficusin/therapeutic use , Fluorouracil/adverse effects , Fluorouracil/therapeutic use , Humans , Middle Aged , Minoxidil/therapeutic use , Prospective Studies , Spironolactone/therapeutic use , Taxoids/therapeutic use , Ultraviolet Therapy , Vitamins/therapeutic use
10.
Crit Rev Oncol Hematol ; 82(3): 361-9, 2012 Jun.
Article in English | MEDLINE | ID: mdl-22024387

ABSTRACT

Prognosis of early breast cancer patients is significantly improved with the use of adjuvant therapies. Various guidelines have been proposed to select patients who will derive the most benefit from such treatments. However, classifications have limited usefulness in subsets of patients such as those with node negative breast cancer. The 2007 St. Paul de Vence Clinical Practice Recommendations proposed to consider adjuvant therapy in accordance with the 10-year relapse-free survival reduction estimated by Adjuvant! Online. However, many limitations remain regarding the use of Adjuvant! Online. Among them, adverse prognostic and/or predictive factors such as vascular invasion, mitotic activity, progesterone receptor negativity, and HER-2 expression are not incorporated in the routine clinical decision process. Our group has therefore issued guidelines based on the consideration of both Adjuvant! Online calculations and the prognostic and/or predictive effects of these markers. In addition, web-accessible comprehensive tables summarizing these recommendations are provided.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Secondary Prevention , Antineoplastic Agents/administration & dosage , Breast Neoplasms/pathology , Cell Proliferation/drug effects , Chemotherapy, Adjuvant , Disease-Free Survival , Drug Administration Schedule , Female , Gene Expression/drug effects , Humans , Internet , Practice Guidelines as Topic , Predictive Value of Tests , Prognosis , Receptor, ErbB-2/genetics , Receptor, ErbB-2/metabolism , Receptors, Progesterone/genetics , Receptors, Progesterone/metabolism
11.
Bull Cancer ; 97(3): 341-8, 2010 Mar.
Article in French | MEDLINE | ID: mdl-20159676

ABSTRACT

The several options for therapy in breast cancer underline the difficulties to determine the reliable population which can be treated by a specific adjuvant therapy, and the population in which that therapy could generate morbidity, mortality, "medical surcharge" without prognosis improvement. This problem is particularly accurate in node-negative breast cancer patients. Adjuvant therapy has been proved to be more efficient, so a better definition of the prognosis and the response to adjuvant treatments could allow the selection of a sub-group of patients who can be spared chemotherapy. The quantification of the uPA/PAI-1 tumor content is one of the most relevant prognostic factors in this clinical setting. The integration of the uPA/PAI-1 prognostic information gathered in the multidisciplinary medical consensus meetings could be used to select the node-negative good/prognosis population in which chemotherapy could be avoided. This review will focus on the uPA/PAI-1 system, its biological role and its clinical implications in breast oncology. The different ways to analyse the uPA and PAI-1 content in tumor cells will be also presented and commented.


Subject(s)
Breast Neoplasms/metabolism , Breast Neoplasms/therapy , Neoplasm Proteins/physiology , Plasminogen Activator Inhibitor 1/physiology , Urokinase-Type Plasminogen Activator/physiology , Biomarkers, Tumor/physiology , Enzyme-Linked Immunosorbent Assay/methods , Female , Humans , Neoplasm Recurrence, Local , Precision Medicine/methods , Prognosis , Receptors, Urokinase Plasminogen Activator/physiology
12.
Crit Rev Oncol Hematol ; 72(3): 265-9, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19596586

ABSTRACT

Shortening duration of chemotherapy-induced neutropenia may reduce risk of infection and aid subsequent chemotherapy delivery. Cycle 1 neutrophil recovery was evaluated in 59 elderly women with breast cancer receiving adjuvant FEC100 (5-fluorouracil 500 mg/m(2), epirubicin 100mg/m(2) and cyclophosphamide 500 mg/m(2)) and randomized to pegfilgrastim primary prophylaxis (PP) from cycle 1, or secondary prophylaxis (SP, i.e., subsequent to a neutropenic event [no G-CSF in cycle 1]). In cycle 1, grade 4 neutropenia occurred in 77% (PP; N=30) and 72% (SP; N=29). Duration of grade 3-4 neutropenia was shorter with pegfilgrastim than without. Mean absolute neutrophil count (ANC) recovered above 1.0 x 10(9)/L by day 9 (pegfilgrastim) versus days 16-18 (without). At last observation (> or =day 14+/-2), no PP patient had ANC <1.0 x 10(9)/L versus approximately 25% of those receiving no pegfilgrastim. In conclusion, cycle 1 pegfilgrastim improved recovery from severe neutropenia in elderly breast cancer patients receiving adjuvant FEC100.


Subject(s)
Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Granulocyte Colony-Stimulating Factor/therapeutic use , Neutropenia/drug therapy , Aged , Antineoplastic Agents/adverse effects , Female , Filgrastim , Humans , Polyethylene Glycols , Recombinant Proteins
13.
Bull Cancer ; 96(3): 285-9, 2009 Mar.
Article in French | MEDLINE | ID: mdl-19318306

ABSTRACT

Adjuvant hormono-radiotherapy applied to breast cancers have been published for many years as an efficient neo-adjuvant treatment. Given the common hormonal dependence of breast cancer and the potential synergistic effect of these two treatment modalities, this strategy has been increasing in the adjuvant setting. Indeed, two strategies are used in daily clinical practice: upfront aromatase inhibitors or sequentially after a variable delay of tamoxifen (TAM). These molecules may thus interact with radiotherapy (RT). Retrospectives studies did not show any differences in terms of loco-regional recurrences between concurrent or sequential radio-hormono-therapy. Lung and skin fibroses due to concurrent treatment are still under debate. Nevertheless, late side-effects appeared to be increased particularly in hypersensitive patients identified by the lymphocyte predictive test. Preliminary results from the phase II randomized study (CO-HO-RT trial) evaluating the impact of concurrent or sequential letrozole and RT on toxicities has recently confirmed the need to identify hypersensitive patients before delivering concurrent systemic therapy with RT.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Neoplasms, Hormone-Dependent/drug therapy , Neoplasms, Hormone-Dependent/radiotherapy , Anastrozole , Chemotherapy, Adjuvant , Female , Humans , Letrozole , Nitriles/therapeutic use , Randomized Controlled Trials as Topic , Tamoxifen/therapeutic use , Triazoles/therapeutic use
14.
Ann Oncol ; 19(7): 1255-1260, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18381372

ABSTRACT

BACKGROUND: Treatment options are limited for patients with refractory metastatic breast cancer (MBC). Larotaxel (XRP9881) is a novel taxoid with preclinical activity against taxane-resistant breast cancer. The current phase II trial of larotaxel was conducted in women with taxane-treated MBC. PATIENTS AND METHODS: Patients were stratified by response to prior taxane therapy (resistant or nonresistant). Larotaxel 90 mg/m(2) was administered as a 1-h infusion every 3 weeks. Patients were evaluated for tumor response every two cycles. A blinded external response review committee determined the overall response rate (ORR), duration of response (DOR), and time to progression (TtP) of the disease. Median survival time (MST) and safety were also evaluated. RESULTS: One hundred and thirty patients were treated. In the nonresistant group, the ORR was 42%; median DOR 5.3 months; median TtP 5.4 months; and MST 22.6 months. In the resistant group, the ORR was 19%; median DOR 5.0 months; median TtP 1.6 months; and MST 9.8 months. The most common grade 3/4 adverse events were neutropenia (82%), fatigue (15%), diarrhea (12%), febrile neutropenia (9%), neutropenic infection (8%), and sensory neuropathy (7%). CONCLUSIONS: Larotaxel has good activity, manageable toxicity, and a favorable therapeutic index in women with taxane-pretreated MBC.


Subject(s)
Antineoplastic Agents/administration & dosage , Breast Neoplasms/drug therapy , Bridged-Ring Compounds/administration & dosage , Taxoids/administration & dosage , Adult , Aged , Antineoplastic Agents/adverse effects , Breast Neoplasms/pathology , Cohort Studies , Diarrhea/chemically induced , Disease Progression , Disease-Free Survival , Drug Administration Schedule , Fatigue/chemically induced , Female , Follow-Up Studies , Humans , Infusions, Intravenous , Kaplan-Meier Estimate , Middle Aged , Neoplasm Metastasis/drug therapy , Neoplasm Metastasis/pathology , Neutropenia/chemically induced , Prospective Studies , Taxoids/adverse effects , Time Factors , Treatment Outcome
15.
Crit Rev Oncol Hematol ; 64(1): 64-72, 2007 Oct.
Article in English | MEDLINE | ID: mdl-17317205

ABSTRACT

This randomized phase 2 study explored the feasibility of delivering four to six cycles of the dose-intensified regimen FEC-100 (5-fluorouracil, epirubicin, and cyclophosphamide) to elderly patients with stage II-III breast cancer, using pegfilgrastim for neutrophil support. Sixty patients aged 65-77 years received single 6mg doses of pegfilgrastim on day 2 of FEC-100, either as primary prophylaxis (all cycles: PP), or as secondary prophylaxis (all cycles following a neutropenic event: SP). Neutropenic events (a composite endpoint that included grade 3 neutropenia+fever, grade 4 neutropenia, infectious complication requiring systemic anti-infectives and chemotherapy dose delay/reduction) occurred in 24/30 (80%) of the PP and 21/29 (72%) of the SP group in the first cycle. Most patients received all chemotherapy cycles at full dose on schedule (26/30 [87%] PP; 20/29 [69%] SP). These data indicate that delivery of FEC-100 is feasible with pegfilgrastim support in elderly breast cancer patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Breast Neoplasms/drug therapy , Granulocyte Colony-Stimulating Factor/administration & dosage , Neutropenia/prevention & control , Aged , Antineoplastic Combined Chemotherapy Protocols/toxicity , Breast Neoplasms/complications , Cyclophosphamide/administration & dosage , Cyclophosphamide/toxicity , Epirubicin/administration & dosage , Epirubicin/toxicity , Female , Filgrastim , Fluorouracil/administration & dosage , Fluorouracil/toxicity , Granulocyte Colony-Stimulating Factor/toxicity , Humans , Neutropenia/chemically induced , Opportunistic Infections/chemically induced , Polyethylene Glycols , Premedication , Recombinant Proteins , Treatment Outcome
16.
Br J Cancer ; 91(7): 1251-60, 2004 Oct 04.
Article in English | MEDLINE | ID: mdl-15328527

ABSTRACT

Concomitant use of adjuvant tamoxifen (TAM) and radiation therapy (RT) is not widely accepted. We aim to assess whether this treatment is associated with an increased risk of developing subcutaneous fibrosis after conservative or radical surgery in breast cancer patients. We analysed 147 women with breast cancer treated with adjuvant RT, and who were included in the KFS 00539-9-1997/SKL 00778-2-1999 prospective study aimed at evaluating the predictive value of CD4 and CD8 T-lymphocyte apoptosis for the development of radiation-induced late effects. TAM (20 mg day(-1)) with concomitant RT was prescribed in 90 hormone receptor-positive patients. There was a statistically significant difference in terms of complication-relapse-free survival (CRFS) rates at 3 years, 48% (95% CI 37.2-57.6%) vs 66% (95% CI 49.9-78.6%) and complication-free survival (CFS) rates at 2 years, 51% (95% CI 40-61%) vs 80% (95% CI 67-89%) in the TAM and no-TAM groups, respectively. In each of these groups, the CRFS rates were significantly lower for patients with low levels of CD8 radiation-induced apoptosis, 20% (95% CI 10-31.9%), 66% (95% CI 51.1-77.6%), and 79% (95% CI 55-90.9%) for CD8 24%, respectively. Similar results were observed for the CFS rates. The concomitant use of TAM with RT is significantly associated with an increased incidence of grade 2 or greater subcutaneous fibrosis; therefore, caution is needed for radiosensitive patients.


Subject(s)
Antineoplastic Agents, Hormonal/adverse effects , Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Radiation Pneumonitis/etiology , Tamoxifen/adverse effects , Tamoxifen/therapeutic use , Adult , Aged , Aged, 80 and over , Apoptosis , CD4-Positive T-Lymphocytes , CD8-Positive T-Lymphocytes , Combined Modality Therapy , Disease-Free Survival , Female , Humans , Middle Aged , Prospective Studies , Risk Factors
17.
Cancer Radiother ; 8(3): 188-96, 2004 Jun.
Article in French | MEDLINE | ID: mdl-15217586

ABSTRACT

Combining radiation and hormone therapy has become common clinical practice in recent years for locally advanced prostate cancer. The use of such concomitant therapy in the treatment of breast disease has been very infrequently reported in the literature, but such an application seems justified given the common hormonal dependence of breast cancer and the potential synergetic effect of these two treatment modalities. As adjuvant therapy, tamoxifen is the key drug in the hormonal treatment arsenal, providing a significant improvement in both local control and global survival rates. Aromatase inhibitors are currently being evaluated in this setting, and initial results are promising. In vitro, tamoxifen does not seem to offer a protective effect against radiation. In clinical use, the few available published studies confirm the superiority of the association of radiation with tamoxifen as opposed to radiation therapy alone in decreasing local recurrences of surgically removed breast tumors. Toxicity associated with such concomitant therapy includes mainly subcutaneous and pulmonary fibroses. However, subcutaneous fibrosis and its cosmetic impact on the treated breast are frequently described side effects of radiation therapy, and their incidence may actually be reduced when tamoxifen is associated. The evidence is less controversial for pulmonary fibrosis, which is more common with the concomitant therapy. The association of radiation and aromatase inhibitors has as of yet rarely been reported. Letrozole (Femara) has a radiosensitizing effect on breast-cancer cell lines transfected with the aromatase gene. Clinical data assessing this effect in vivo are not available. The FEMTABIG study (letrozole vs. tamoxifen vs. sequential treatment) did not specify the sequence of radiation and hormonal therapy. The ATAC study comparing the adjuvant use of anastrozole (Arimidex) and tamoxifen does not provide any information on the number of patients receiving radiation concomitant with the hormonal treatment, and in addition also does not specify the sequence of radiation and hormonal treatment. The TEAM study compared exemestane (Aromasine) and tamoxifen, but specified that hormonal treatment follow the completion of radiation therapy.


Subject(s)
Antineoplastic Agents, Hormonal/therapeutic use , Breast Neoplasms/drug therapy , Breast Neoplasms/radiotherapy , Adult , Aromatase Inhibitors , Breast Neoplasms/surgery , Chemotherapy, Adjuvant , Clinical Trials as Topic , Combined Modality Therapy , Female , Humans , Prognosis , Radiotherapy, Adjuvant , Tamoxifen/therapeutic use
20.
Cancer Radiother ; 6(4): 238-58, 2002 Jun.
Article in French | MEDLINE | ID: mdl-12224489

ABSTRACT

CONTEXT: The "Standards, Options and Recommendations" (SOR) project, started in 1993, is a collaboration between the Federation of french cancer centers (FNCLCC), the 20 french cancer centers, and specialists from french public universities, general hospitals and private clinics. The main objective is the development of clinical practice guidelines to improve the quality of health care and the outcome of cancer patients. The methodology is based on a literature review and critical appraisal by a multidisciplinary group of experts, with feedback from specialists in cancer care delivery. OBJECTIVES: To develop clinical practice guidelines for non metastatic breast cancer patients according to the definitions of the Standards, Options and Recommendations project. METHODS: Data were identified by searching Medline, web sites, and using the personal reference lists of members of the expert groups. Once the guidelines were defined, the document was submitted for review to 148 independent reviewers. RESULTS: This article presents the chapter radiotherapy resulting from the 2001 update of the version first published in 1996. The modified 2001 version of the standards, options and recommendations takes into account new information published. The main recommendations are: (1) Breast irradiation after conservative surgery significantly decrease the risk of local recurrence (level of evidence A) and the decrease in the risk of local recidive after chest wall irradiation is greater as the number of risk factors for local recurrence increases (level of evidence A). (2) After conservative surgery, a whole breast irradiation should be performed at a minimum dose of 50 Gy in 25 fractions (standard, level of evidence A). (3) A boost in the tumour bed should be performed in women under 50 years, even if the surgical margins are free (standard, level of evidence B). (4) Internal mammary chain irradiation is indicated for internal or central tumours in the absence of axillary lymph node involvement (expert agreement) and in the presence of lymph node involvement (standard, level of evidence B1). (5) Sub- and supra-claviculr lymph node irradiation is indicated in patients with axillary node involvement (standard, level of evidence B1).


Subject(s)
Breast Neoplasms/radiotherapy , Carcinoma, Ductal, Breast/radiotherapy , Radiotherapy, Adjuvant/standards , Adult , Aged , Breast Implants , Breast Neoplasms/surgery , Clinical Trials as Topic , Europe/epidemiology , Expert Testimony , Female , France , Humans , Lymphatic Irradiation/adverse effects , Lymphatic Irradiation/standards , Lymphatic Metastasis , Lymphedema/etiology , Mastectomy/methods , Meta-Analysis as Topic , Middle Aged , Multicenter Studies as Topic/statistics & numerical data , Neoplasm Recurrence, Local/prevention & control , Radiation Injuries/etiology , Radiotherapy Dosage , Radiotherapy, Adjuvant/adverse effects , Randomized Controlled Trials as Topic , Retrospective Studies , Survival Analysis
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