Safety of a novel capecitabine dosing schedule when combined with lapatinib in patients with HER2-positive metastatic breast cancer refractory to trastuzumab

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1131-1131
Author(s):  
T. A. Traina ◽  
M. Theodoulou ◽  
K. Feigin ◽  
S. Patil ◽  
S. Geneus ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Optimal Schedule ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Ecog Performance Status ◽  
Study Results ◽  
Her 2 ◽  
Ecog Ps

1131 Background: Capecitabine (C) is active in breast cancer and is usually dosed for 14 days (d) followed by a 7d rest (14 - 7). We described a mathematical method which predicts the optimal schedule for C to be 7d followed by a 7d rest (7 - 7) (Norton et al, Amer Assn Can Res. 2005). The MTD of C(7 - 7) is 2,000mg BID (Traina et al, J Clin Oncol. April 2008). Lapatinib (L) improves time to progression when added to C(14 - 7) in patients (pts) with HER-2-positive (+) metastatic breast cancer (MBC) that progressed after trastuzumab (T). To optimize this effective combination, we are testing C(7 - 7) + L in a phase II trial. Methods: Eligible pts have measurable, HER-2(+) MBC that has progressed after T. HER-2(+)=IHC 3+ or FISH>2. Pts have normal LVEF by MUGA, ECOG performance status (PS) <2 and normal organ function. <3 prior chemotherapy (CRx) regimens are permitted. Prior fluoropyrimidine is excluded. Therapy (tx) consists of C (2,000 mg BID, 7 - 7) and L (1,250 mg, daily). Cycle length = 4 wk. Pts are evaluated for toxicity q4 weeks (wk), for response q12wk; LVEF by MUGA q12wk. Primary endpoint: response rate (RR). Secondary endpoints: toxicity, stable disease >6 months, PFS. Using a Simon optimal 2-stage design, with alpha = 10%, power = 90% to discriminate between RR 10% and 25%, 21 pts will be accrued to the first stage. If >2 pts respond, 29 additional pts will be enrolled. If >7/ 40 pts respond, then C(7 - 7) + L will be considered worthy of further study. Results: As of January 5, 2008, 6 pts are enrolled and evaluable. Median (med) age 64 yrs (42–71), med ECOG PS 1 (0–1), ER/PR(+) 3, HER-2(+) 6, sites of MBC: bone (2), viscera (4), soft tissue (5). Med baseline LVEF 62% (51–68%). Prior tx: Adjuvant: CRx (5), hormone tx (3), T (3); MBC: CRx (2), hormone tx (1), T (3). After a med of 3 cycles (1–4), there were no grade 3, 4, or 5 events. Tx-related toxicity is: Gr 2 fatigue (1); Gr 1 AST (4), diarrhea (3), ALT (2), vomiting (1), hand-foot (1), fatigue (1). No withdrawls due to reduced LVEF. Two pts evaluable for response: PR = 1, SD<6 mo = 1. Conclusions: Capecitabine (7 - 7) + lapatinib appears well tolerated compared to C(14 - 7)+L (Geyer et al). Additional safety and efficacy data is anticipated prior to this meeting. [Table: see text]

Metronomic cyclophosphamide and capecitabine combined with lapatinib in heavily pretreated metastatic breast cancer (MBC) HER2-positive patients: 2-year update.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11515-e11515
Author(s):  
Katia Cagossi ◽  
Giorgia Razzini ◽  
Alessia Ferrari ◽  
Maria Grazia Lazzaretti ◽  
Meri Leporati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Heavily Pretreated ◽  
Her 2

e11515 Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, prior systemic therapy for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression. Primary objective was time to progression (TTP) and safety. Results: Fifteenpatients were included. Median age was 52 years old (range 42-77). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 6 months (2-14). No complete response was observed. Eight out of fiftten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and were still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited significant reduction of serum marker concentrations. No grade 3-4 skin toxicity was reported. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The combination of lapatinib with metronomic chemotherapy may lead to effective palliation despite extensive pretreatment at least in bone metastatic patients. The treatment appears to be less toxic than lapatinib and capecitabine at full dosage, especially in heavily pretreated MBC patients. The preliminary results suggest the need of a clinical trial to confirm a role of this combination to delay lapatinib resistance.

Randomized Phase II Trial of First-Line Trastuzumab Plus Docetaxel and Capecitabine Compared With Trastuzumab Plus Docetaxel inHER2-Positive Metastatic Breast Cancer

2010 ◽  
Vol 28 (6) ◽  
pp. 976-983 ◽  
Author(s):  
Andrew M. Wardley ◽  
Xavier Pivot ◽  
Flavia Morales-Vasquez ◽  
Luis M. Zetina ◽  
Maria de Fátima Dias Gaui ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Performance Status ◽  
Locally Advanced ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
First Line ◽  
Her2 Positive ◽  
Grade 3

PurposeTo evaluate trastuzumab (H) and docetaxel (T) with or without capecitabine (X) as first-line combination therapy for human epidermal growth factor receptor 2 (HER2) -positive advanced breast cancer.Patients and MethodsPatients with HER2-positive locally advanced or metastatic breast cancer were randomly assigned to H (8 mg/kg loading; 6 mg/kg every 3 weeks) plus T (75 mg/m2in HTX arm, 100 mg/m2in HT arm, every 3 weeks) with or without X (950 mg/m2twice per day on days 1 to 14 every 3 weeks). The primary end point was overall response rate (ORR).ResultsIn 222 patients, median follow-up was approximately 24 months. ORR was high with both regimens (70.5% with HTX; 72.7% with HT; P = .717); complete response rate was 23.2% with HTX compared with 16.4% with HT. HTX demonstrated significantly longer progression-free survival: median 17.9 months compared with 12.8 months with HT (hazard ratio, 0.72; P = .045), which translates to a gain of around 5 months. Two-year survival probability was 75% with HTX compared with 66% with HT. Febrile neutropenia (27% v 15%) and grade 3/4 neutropenia (77% v 54%) incidences were higher with HT than HTX. Treatment-related grade 3 hand-foot syndrome (17% v < 1%) and grade 3/4 diarrhea (11% v 4%) occurred more commonly with HTX than HT. One case of congestive heart failure occurred in each arm.ConclusionHTX is an effective and feasible first-line therapy for HER2-positive locally advanced or metastatic breast cancer, although it should be reserved for patients with good performance status who are not receiving long-term steroids.

Changes in circulating endothelial cells (CEL) in patients receiving trastuzumab for metastatic breast cancer predict response to treatment

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 579-579
Author(s):  
P. Spadaro ◽  
M. Ingemi ◽  
G. Dottore ◽  
G. Toscano ◽  
R. Maisano
Keyword(s):  
Breast Cancer ◽  
Endothelial Cells ◽  
Metastatic Breast Cancer ◽  
Performance Status ◽  
Antiangiogenic Therapy ◽  
Metastatic Breast ◽  
Circulating Endothelial Cells ◽  
Response To Treatment ◽  
Breast Cancer Patients ◽  
Her 2

579 Background: Amplification or overexpression of HER-2/neu has been identified in 10–20% of invasive breast cancers and is associated with shorter overall survival times; furthermore HER-2/neu is a predictive factor with regard to monoclonal antibody therapy with Trastuzumab. The observed association between the overexpression of HER-2/neu and higher VEGF expression indicates that HER-2/neu is involved, at least partly, in the regulation of angiogenesis in human breast cancer. Recently circulating endothelial cells (CECs) have been proposed as a marker of tumor progression and/or a response to antiangiogenic therapy; thus, we have performed a phase II study to explore the correlation between CECs and treatment with Trastuzumab in metastatic breast cancer Methods: 22 women aged ≥ 18 years with histologically proven Her-2-positive, ECOG performance status 0 to 2 who were not eligible for, or who wished to delay receiving chemotherapy received a standard loading dose of Trastuzumab 4 mg/Kg followed by 2 mg/Kg weekly. The weekly maintenance dose was continued until disease progression. A panel of monoclonal antibodies including anti CD45 to exclude hematopoietic cells, anti CD31, CD34, CD36, CD105, CD106, CD133, and KDR and appropriate analysis gates were used to enumerate resting and activated circulating endothelial cells Results: The overall response rate (RC + RP) to treatment was 25% (2 RC + 3RP). In healthy controls (N° 20) mean values of resting and activated CECs were 7.6/μL (4.6 - 11.2/μL) and 1.3/μL (0.1 - 2.4 /μL) respectively. Before treatment with Trastuzuamb the mean resting and activated CECs were 41.1/μL (16.4 - 60.5/μL) and 6.9/μL (5.1 - 8.7/μL). At a first assessment (6 wks) a significant decrease in CECs (p<0.001)was found in patients responding to treatment but not in the patients who did not achieve a remission Conclusions: Our finding has shown that resting and activated CECs are increased in metastatic breast cancer patients and decline during treatment in responding patients, furthermore, these data underline the crucial role of angiogenesis in this setting and support the rationale for a combination of Bevacizumab with Trastuzumab. No significant financial relationships to disclose.

Phase II evaluation of liposomal doxorubicin combined with docetaxel in patients with metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1112-1112
Author(s):  
J. Fasano ◽  
D. Hershman ◽  
Y. Novik ◽  
K. Blozie ◽  
A. Tiersten
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Liposomal Doxorubicin ◽  
Performance Status ◽  
Metastatic Breast ◽  
Time To Progression ◽  
Ecog Performance Status ◽  
Weekly Docetaxel ◽  
Mixed Response ◽  
Response To Chemotherapy

1112 Background: The combination of anthracyclines and taxanes are effective in the treatment of metastatic breast cancer. Liposomal doxorubicin has been shown to be as effective as doxorubicin with less toxicity and it can be combined safely with docetaxel. Methods: Monthly liposomal doxorubicin (30 mg/m2) in combination with weekly docetaxel (30 mg/m2) was evaluated in women with metastatic breast cancer. Cycles were continued until disease progression or unacceptable toxicity. Radiologic assessment was performed every two months. The primary outcome was time to progression. Secondary endpoints included overall response rate, median survival and toxicity. Results: Between 12/2002 and 9/2005, 12 women were enrolled and received this combination as front- line chemotherapy for metastatic breast cancer. The mean age was 46.5 (31–60) years. Nine (75%) patients had tumors that were ER+ or PR+. Five (41.7%) women had tumors that over-expressed her-2/neu. Ten women had an EGOG performance status of 1. Two women had an ECOG performance status of 2. The median number of cycles received was 4 (1–12). Four (25%) women were taken off study due to intolerable toxicity and 7 (58.3%) due to progressive disease. One (8.3%) woman remains progression free. Ten (83.3%) women had a partial response, one (8.3%) woman had a mixed response and one (8.3%) was not evaluable for response to chemotherapy. The median time to progression was 21 (6–52) weeks. Three women remain alive with disease. One woman remains alive and progression-free. Ten (83%) patients experienced Grade 3/4 toxicities, including: stomatits 6 (50%), nausea/vomiting 1 (8.3%), neutropenia 3 (25%), infection 3 (25%), dyspnea 2 (16.7%), and PPE 1 (8.3). Conclusions: Monthly liposomal doxorubicin plus weekly docetaxel in women with metastatic breast cancer resulted in an encouraging response, but was difficult to tolerate. Further evaluation of this combination with improved supportive care may be warranted. [Table: see text]

Metronomic cyclophosphamide and capecitabine combined with lapatinib in heavily pretreated metastatic breast cancer (MBC) HER2-positive patients.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11071-e11071
Author(s):  
Katia Cagossi ◽  
Maria Grazia Lazzaretti ◽  
Alessia Ferrari ◽  
Giorgia Razzini ◽  
Meri Leporati ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Bone Metastases ◽  
Kinase Inhibitor ◽  
Performance Status ◽  
Metastatic Breast ◽  
Metronomic Chemotherapy ◽  
Breast Cancer Patients ◽  
Heavily Pretreated ◽  
Her 2

e11071 Background: Current therapeutic goals for MBC, as an incurable disease, are symptoms and prolonged disease control together with good quality of life. Metronomic chemotherapy has shown efficacy in patients with metastatic breast cancer. We evaluated the efficacy and tolerability of the combination of anti-angiogenetic activity of metronomic chemotherapy with a tyrosine kinase inhibitor such as lapatinib in heavily pre-treated MBC HER-2 positive patients. Methods: Metastatic breast cancer patients HER-2 positive with CEA or Ca15.3 elevated, measurable disease, prior systemic therapy (chemotherapy and/or hormonal therapy) for advanced disease, ECOG performance status < 1 and life expectancy longer than 3 months. MBC patients were treated with metronomic oral capecitabine (1500 mg daily) and cyclophosphamide (50 mg daily) plus lapatinib (1250 mg daily). The treatment was given until disease progression or unacceptable toxicity. Primary objective was time to progression (TTP) and safety. Results: Tenpatients were included. Median age was 56 years old (range 46-76). Median number of previous chemotherapy lines was 5 (range 2-10). Median time to tumor progression was 4 months (2-7). No complete response was observed. Six out of ten patients (60%) with pre-existing only bone metastases achieved a stable disease and/or partial response and are still on treatment after 6 month of therapy. At the same time 100% of these patients exhibited reduction of serum marker concentrations to normal range. No grade 3-4 toxicity was reported. There was no decline in cardiac function. Hematological and gastro-intestinal toxicity was well tolerated (G1-2). No reduction of dose was needed. Conclusions: The treatment appears to be an effective and less toxic option in heavily pretreated MBC patients. Of note is the observed activity in patients with exclusive bone metastases. Monitoring of CEA and Ca15.3 during the first two months of treatment appears to provide a sensitive and economical means of identifying those patients who are responding to the therapy. Therefore, the combination of lapatinib with metronomic chemotherapy should be explored in advance for osseous MBC.

scholarly journals Eribulin Mesylate in Treated Metastatic Breast Cancer Patients: A Retrospective Study of Tumor Response and Adverse Effects

2021 ◽  
Vol 6 (2) ◽  
pp. 37-44
Author(s):  
Bindu SM ◽  
PL Rema ◽  
Praveen Jacob Ninan
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Retrospective Study ◽  
Tumor Response ◽  
Performance Status ◽  
Metastatic Breast ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Ecog Performance Status ◽  
Eribulin Mesylate

Introduction: Breast cancer is the most common cancer, majority of patients present in advanced stage and 30% develop distant metastasis. Metastatic Breast Cancer (MBC) is not curable and treatment aims at prolongation of life with good palliation. There is no standard treatment, though the usual first and second lines of chemotherapy include anthracyclines and taxanes. The third line chemo drugs available are gemcitabine, capecitabine, vinorelbine and eribulinmesylate Materials and Methods: This is a retrospective study of MBC patients pretreated with anthracyclines and taxanes and then received 4 cycles of eribulin during the period March 2015-2017 in Medical College, Alappuzha and aims at studying the tumor response and drug toxicities. The tumor response is studied using CR-complete response, PR- partial response, PD-progressive disease and SD-stable disease. Results: There were a total of 18 patients, majority of whom were below 50 years. ECOG performance status of 0-1 was found in 83.3% and 77.8% were receptor positive. No patient had CR, 66.7% of patients had PR, 22.2% had PD and 11.1% had SD. 61.1% of patients who had a PR had good performance status.55.6% of patients who were ERPR positive had a PR and 44.4% patients who were Her2neu positive had a PR. Most common toxicities detected were alopecia (83.3%), neutropenia (72.2%), fatigue (72.2%) and neurotoxicity (55.6%). Conclusion: Eribulin mesylate is a drug having good response with tolerable toxicities and can be considered in our population. Keywords: Metastatic breast cancer, eribulin mesylate, capecitabine.

scholarly journals The Difference in Clinical and Prognostic Features Between De Novo and Recurrent Her2-Positive Metastatic Breast Cancer Patients

Acta Medica ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 14-19
Author(s):  
Yusuf Acikgoz ◽  
Yakup Ergun ◽  
Gokhan Ucar ◽  
Merve Dirikoc ◽  
Dogan Uncu
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Survival Data ◽  
De Novo ◽  
Metastatic Breast ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Her2 Positive ◽  
Prognostic Features ◽  
Her 2

Abstract   BACKGROUND: There are different data in the literature about the consequences of the development of metastasis as de novo or recurrent. In this study, we retrospectively investigated the clinicopathologic and prognostic characteristics of HER-2 positive de novo and recurrent metastatic breast cancer (MBC) patients. PATIENTS AND METHODS: The data of patients admitted to our clinic between 1996-2017 were analyzed retrospectively. The baseline features, treatments and survival data were recorded. Recurrent metastatic patients were further categorized as disease free interval (DFI) <24 months and DFI >24 months. The features of two groups were analyzed by pearson chi-square test. Survival were calculated by using the Kaplan-Meier method with the Long-rank test. p <0.05 was considered statistically significant. RESULTS: A total of 44 patients were included to study in which 20 patients in de novo HER-2 positive MBC group and 24 patients in recurrent HER-2 MBC group. There was no difference in baseline features between groups. The median OS in de novo and recurrent MBC group was 60.3 months and 43.9 months respectively (HR: 0.87, 95% CI 0.37-2.05, p=0.76). OS was not different between de novo MBC group and patients with DFI <24 months and with DFI > 24 months (p=0.135). CONCLUSION: Our study showed that baseline features of patients with de novo HER-2 positive MBC and recurrent HER-2 positive MBC did not differ from each other. The presence of metastasis at the time of diagnosis or during follow-up did not change response to treatments.  

scholarly journals A Prospective, Randomized, Placebo-Controlled Study of a Combination of Simvastatin and Chemotherapy in Metastatic Breast Cancer

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Hiba Alarfi ◽  
Lama A. Youssef ◽  
Maher Salamoon
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Controlled Trial ◽  
Performance Status ◽  
Objective Response ◽  
Metastatic Breast ◽  
High Sensitivity ◽  
Controlled Study ◽  
Ecog Performance Status ◽  
Baseline Values

Preclinical studies support the anticancer activity of statins; however, the existing clinical evidence is inconsistent and not definitive. Our study aimed at evaluating a postulated cancer chemo-sensitizing effect of statin (simvastatin) in a cohort of metastatic breast cancer (MBC) patients. We designed a prospective, single-centered, randomized, double blinded, placebo-controlled trial that encompassed MBC patients with an ECOG Performance Status Scale ≤2 and scheduled to be treated with a chemotherapy regimen consisting of carboplatin and vinorelbine every 3 weeks at Al-Baironi Hospital, Damascus, Syria. Patients were enrolled between August 2011 and July 2012 and randomly allocated to receive a 15-day course of either simvastatin (40 mg) or placebo seven days prior to the first day of each chemotherapy cycle and then continued for eight days in each individual cycle. Primary endpoints were objective response rate (ORR) and toxicity, and the secondary endpoint was overall survival (OS). Eighty-two patients met the inclusion criteria and consented. ORR (35% vs. 32.5%) and predominant toxicity and grade ≥3 neutropenia (occurred in 30% vs. 40% of the patients) were not significantly different between simvastatin and placebo groups, respectively. Over a median follow-up of 44 months (range, 10–60), median OS was 15 months in the simvastatin group and 17 the in placebo group (hazard ratio (HR) = 1.16, 95% CI (0.70–1.91), P=0.57). Elevated baseline values of high-sensitivity C-reactive protein (hsCRP >10 mg/l), lactate dehydrogenase (LDH >480 U/L), and chemotherapy being ≥2nd line were significantly associated with shorter OS for the total cohort in both Univariate and multivariate analyses. Our data prove a safe profile of simvastatin at 40 mg per day combined with carboplatin and vinorelbine in MBC patients but without any beneficial increase of tumor sensitivity to chemotherapy. Moreover, we demonstrated a strong clinical advantage of baseline values of hsCRP and LDH as useful prognostic tools in MBC patients. This trial is registered with ISRCTN12964275.

Safety of long-term administration of capecitabine in metastatic breast cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10755-10755
Author(s):  
M. Lomas ◽  
J. Salvador ◽  
M. Ruiz ◽  
J. L. Bayo
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Cancer Patients ◽  
Performance Status ◽  
Metastatic Breast ◽  
Term Treatment ◽  
Breast Cancer Patients ◽  
Ecog Performance Status ◽  
Long Term Treatment

10755 Background: To evaluate the effectiveness and tolerability of long -term treatment with capecitabine in metastatic breast cancer patients. Capecitabine (C) has been administered offering clinical benefit to women with metastatic breast cancer (MBC) (ORR: 42%). The aim of this trial was to evaluate the efficacy and tolerance of capecitbine in long-term treatment, administered as first, second and third line treatment in MBC. Methods: Patients ≥ 18 years old with MBC, ECOG performance status (PS) ≤2, HER-2 neu negative, non-chemotherapy naive were included in this prospective, multicentre, non-randomized. To date, twenty-two ambulatory patients were evaluable for toxicity and response. Median age 59.2 years (37–81). All of patients had previously received adjuvant treatment. Hormonal therapy were allowed as clinically required. They received three weekly cycles of oral capecitabine 1000–1250 mg/m2 twice daily, days 1–14, followed one week rest until progression or relapse. Results: The overall response rate (ORR) is including PR, CR, and EE 78%. The median treatment duration was 14 months, median range (3–32). Median progression-free and overall survival have not yet been reached. The most common grade ½ (NCIC CTC) treatment related adverse events were /23, hand foot syndrome 4/23, diarrea 1/23. Conclusions: These preliminary data confirm that the treatment with capecitabine (C) is an effective and well tolerated regiment in metastatic breast cancer patients. No significant financial relationships to disclose.

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