Taxanes Research Articles

A randomized, open-label, multicenter, adaptive phase 2/3 study of trastuzumab emtansine (T-DM1) versus a taxane (TAX) in patients (pts) with previously treated HER2-positive locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma (LA/MGC/GEJC).

5 Background: Trastuzumab (H) + capecitabine/fluorouracil + cisplatin is standard of care for 1st-line HER2-positive MGC/GEJC but there is no established HER2-targeted 2nd-line regimen. T-DM1 (H linked to DM1) is approved for HER2-positive metastatic breast cancer previously treated with H + TAX (separately or in combination). This and preclinical HER2-positive GC models provided the rationale for GATSBY (NCT01641939). Methods: GATSBY is a 3-arm randomized, adaptive, seamless phase 2/3 global study of T-DM1 vs TAX in pts with HER2-positive (immunohistochemistry [IHC] 3+ or IHC 2+/in situ hybridization-positive), unresectable LA/MGC/GEJC who progressed during or after 1st-line fluoropyrimidine + platinum ± HER2-targeted therapy. Pts were initially randomized 2:2:1 to T-DM1 3.6 mg/kg every 3 weeks (q3w), T-DM1 2.4 mg/kg weekly (qw), or physician’s choice of paclitaxel 80 mg/m2 qw or docetaxel 75 mg/m2q3w. An independent data monitoring committee selected T-DM1 qw for further study and subsequent patients were randomized 2:1 to this or TAX. The primary endpoint is overall survival (OS); all T-DM1 qw data are analyzed, including dose selection. Results: At clinical cutoff, 06/30/15, 415 pts had been randomized overall: 228 to T-DM1 qw, 117 to TAX (70 T-DM1 q3w pts reported separately); 77.4% had prior HER2-targeted therapy; 29.9% prior gastrectomy; 46.1% were Asian. Efficacy/safety are tabulated. Conclusions: T-DM1 2.4 mg/kg qw did not show an efficacy benefit over TAX. Grade ≥3 AE rates were numerically lower with T-DM1 vs TAX and rates of SAEs, fatal AEs, and treatment discontinuations due to AEs were comparable between arms. Clinical trial information: NCT01641939. [Table: see text]

The occurrence of chemotherapy-induced amenorrhea in postoperative and premenopausal patients with breast cancer and its influencing factors

Objective To study the influence of postoperative chemotherapeutic regimens on menstruation in pre-menopausal patients with breast cancer. Methods 120 pre-menopausal patients with breast cancer from Jan 2010 to Dec 2012 were followed-up. The occurrence rate and recovery rate of chemotherapy-induced amenorrhea (CIA) were analyzed. The relationship between different chemotherapeutic regimens and CIA of various age groups was analyzed. Results 120 women were followed-up, 94 (78.3 %) patients developed CIA. The frequency of CIA in younger patients (≤ 35 years) was significantly lower than that in patients older than 35 years (P 0.05). Conclusions Age is an important influence factor of the CIA. Chemotherapy has less influence on the menstruation of younger patients (≤35 years) and most amenorrhea is reversible. The effects of sequential addition of taxanes in chemotherapy and anthracyclines alone on menstruation have no significant difference. Key words: Breast neoplasms; Chemotherapy; Ovarial function; Amenorrhea

Oral 1.01: Phase II trial of amrubicin in patients with previously treated advanced thymic malignancies

Background Limited treatment options exist for patients with thymic malignancies (TM), and chemotherapy efficacy is often restricted by cumulative toxicity such as neuropathy (taxanes) and cardiomyopathy (anthracyclines). Single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor with minimal cardiac toxicity, was investigated in TM patients in this trial.

Report of ITMIG 2015 Meeting.

Background: Limited treatment options exist for patients with thymic malignancies (TM), and chemotherapy efficacy is often restricted by cumulative toxicity such as neuropathy (taxanes) and cardiomyopathy (anthracyclines). Single agent amrubicin, a third generation anthracycline and topoisomerase II inhibitor with minimal cardiac toxicity, was investigated in TM patients in this trial. Methods: This was an open-label single drug trial at two institutions in the United States (Stanford University and Indiana University). Eligible patients had TM [thymoma (T) or thymic carcinoma (TC)] with progression or relapse after at least one prior chemotherapy regimen, and adequate organ function including left ventricular ejection fraction (LVEF) of >50%. The initial treatment plan consisted of amrubicin at 40 mg/m 2 IV days 1–3 repeated in 3-week cycles. Results: From July 2011 to April 2014, a total of 33 patients (14T/19TC) were enrolled. There were 14 women and 19 men; age range of 30–81 years; 9 Asian, 1 African-American, 1 Hispanic and 22 non-Hispanic White patients. A high rate of febrile neutropenia (FN) led to an amended starting dose of 35 mg/m 2 days 1–3 repeated in 3-week cycles. In total, 7 patients experienced FN with 1 related death. Other grade 3/4 related events included: thrombocytopenia (n=2), neutropenia without fever (n=3), hyponatremia (n=2), hypokalemia (n=2), anemia (n=7), lethargy/fatigue (n=7), perirectal abscess (n=2), palmar-plantar erythrodysesthesia (n=3), syncope (n=2), venous embolism (n=2), and 1 patient each with sepsis, oral abscess, mucositis, chest pain, and epigastric pain. Other toxicities were generally mild and well tolerated. No significant changes in LVEF were noted on serial echocardiograms. There were 6 partial responses (4T/2TC), 21 with stable disease, and 4 with progressive disease (PD) or death at or before first assessment for a response rate (RR) of 18% and a disease control rate (DCR) of 88% (29%/11% RR in T vs . TC and 100%/78% DCR in T vs. TC). All but 5 patients received at least 4 cycles, and 15 tolerated >10 cycles, with 38 cycles as the highest number to date. Three patients remain on therapy. Conclusions: Amrubicin, at 35 mg/m 2 IV days 1–3 on a 3-week cycle, shows promise as a single agent in pre-treated patients with T and TC with an 18% RR (29% T/11% TC) and no unexpected toxicity. DCRs of 100% in the T patients and 78% in the TC patients were observed. RR and DCR were higher in the T patients compared to the TC patients. Further exploration of amrubicin as a single drug or in combination is warranted in TM.

Neoadjuvant chemotherapy for locally advanced cancer

Neoadjuvant chemotherapy is one of the common means in multidisciplinary treatment of locally advanced breast cancer, with anthracyclines and taxanes as main chemotherapeutic drugs. In recent years, molecular target agents have significantly improved the efficacy of chemotherapy, as well as have provi-ded more choices and ideas for clinical treatment. Currently, the widely studied molecular targeted drugs include trastuzumab, lapatinib, pertuzumab, T-DM1 and bevacizumab. Key words: Breast neoplasms; Neoadjuvant chemotherapy

PO62 FIRST LINE TRASTUZUMAB-BASED THERAPY IN HER2-POSITIVE METASTATIC BREAST CANCER PATIENTS PRESENTING WITH DE NOVO OR RECURRENT DISEASE: A MULTICENTER RETROSPECTIVE COHORT STUDY

s / The Breast 24 S3 (2015) S21–S75 S43 this setting. In order to improve pts’ comfort using the oral form of V, we conducted a multicenter phase II study to investigate efficacy and safety of the oral V-T (OVT) combination. Methods: Main eligibility criteria: HER-2Neu positive disease (3+ IHC or FISH+), no adjuvant CT within the last 6 months and no prior CT for MBC. Pts were treated with oral V (oV) 80 mg/m2 D1, D8, D15 (following first 3 administrations at 60 mg/m2 during the first cycle) for a total of 8 cycles (1 cycle = 3 weeks); in combination with (T) 6 mg/ kg on D1 (loading dose, 8 mg/kg) every 3 weeks or 4 mg/kg (loading dose, 6 mg/kg) weekly. Continuation and schedule of (T) were at investigator’s discretion. Response was evaluated every 2 cycles using RECIST 1.0.Primary endpoint: Objective response rate (ORR); secondary EPs: Duration of response (DOR), progression free survival (PFS), overall survival (OS), safety. Results: In the full population (n=26), median age was 50.7 years (range 31.3-80.7); median WHO PS 0 (range 0-1). 69% of pts were postmenopausal and 65% took prior (neo)adjuvant CT. Early stage treatment consisted of a combination of anthracyclines (AC) and taxanes (TX) in 27% of pts. Overall 46% of the pts were pretreated by AC, 38.5% by TX. Median disease free interval was 50.7 (95% CI [43.6-57.9]) months (m). Most frequent metastatic sites were bone (61.5%), liver (50%) and lymph nodes (42%). 73% of pts had 2 or more metastatic sites. A median of 8 oVT cycles were given (range: 3-12): 19% of oV doses were not escalated to 80mg/m2 starting cycle 2. 92% of pts administered T every 3 weeks. In the evaluable pts population, ORR was 56% (95% CI [34.9-75.6]), including 3 complete responses (12%) and 11 partial (44%), 8 pts (32%) had stable disease resulting in a clinical benefit [or disease control] rate of 88 % (95% CI [68.8-97.5]). Median DOR was 7.1m (95% CI [3.9-10.2]). At the time of the analysis, median PFS was 6.7m (95% CI [3.5-10]) and median OS 27.9m (95% CI [17.4-38.3]). Treatment was generally well tolerated with main observed grade 3-4 hematological toxicities being neutropenia (46%) and anemia (4%). Grade 3-4 nausea-vomiting were observed in 11.5% of pts. Conclusion: Our results confirm the efficacy of OVT combination as a first line treatment in Her2 Neu+ LA or MBC pts with an acceptable safety profile. OVT optimizes the convenience of this CT regimen, especially for the pts receiving T every 3 weeks.

P1-5-16 - Exploratory analysis of prognostic subset in esophageal cancer patients previously treated with FU, Pt, taxane therapy

Purpose: To explore the favorable or unfavorable subsets of patients with recurrent or metastatic esophageal squamous cell carcinoma (R/M ESCC) previously treated with fluorouracil (FU), platinum (Pt), and taxane (TAX) therapy. Methods: From March 2003 to November 2014, information on 285 consecutive patients with R/M ESCC who are refractory to or who are not tolerable to all three kinds of drugs (FU, Pt, and TAX therapy) at three institutions was reviewed. Uni- and Multi-variate analyses were performed in study patients for evaluating prognostic factors. Results: Multivariate analyses showed that best supportive care (vs. treatment, HR 2.02, p < 0.001), rare organ metastases (organ metastases except for lung, liver, bone, or lymph node metastases) (vs. absent, HR1.81, p < 0.001), hemoglobin (Hb) <10 g/dl (vs. ≥10 g/dl, HR 1.47, p = 0.014), C-reactive protein (CRP) ≥1.0 mg/dl (vs. <1.0 mg/dl, HR1.47, p = 0.008), and sum of longest diameter of target lesions by Response Evaluation Criteria in Solid Tumor (RECIST) ≥50 mm (vs. <50 mm, HR1.53, p = 0.003) were associated with poor prognosis. Multivariate analysis for significant prognostic factors in CTx group showed that performance status 2 (vs. 0-1, HR 2.41, p = 0.011), lymph node metastases (vs. absent, HR 2.24, p = 0.008), rare organ metastases (vs. absent, HR 2.14, p = 0.006), and CRP ≥ 1.0 mg/dl (vs. <1.0mg/dl, HR 1.87, P = 0.006) relate to OS. Conclusion: Treatment, rare organ metastases, Hb, CRP, and sum of longest diameter of target lesions by RECIST might be independent prognostic factors in patients with R/M ESCC previously treated with FU, Pt, and TAX therapy.

Neoadjuvant Chemotherapy A New Therapeutic Challenge in Treatment of Ovarian Cancer- A Review

As per literature survey reveals that ovarian cancer is the most lethal gynecologic malignancy in females all over the world. In majority of patients who suffering from ovarian cancer clinical complete remissions are obtained through combinations of cytoreductive surgery and chemotherapy. This review represents an overview of the origin of ovarian cancer, history of chemotherapeutic regimens and also focused on chemotherapeutic agents which are useful in the treatment of ovarian cancer. Taxanes are most promising drug used in neoadjuvant chemotherapy. This review adds better advances in medical field may be based on the better understanding of drugs regimens and better control of cost in routine practice which opens the new doors for neoadjuvant chemotherapy which proves a better option in ovarian cancer treatment.

Efficacy and toxicity of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes

To assess the efficacy of vinorelbine (NVB)-based regimens in patients with metastatic triple negative breast cancer (mTNBC) pretreated with anthracyclines and taxanes. Clinical data of 48 patients diagnosed and treated for mTNBC between 2004 and 2012 at the Cancer Hospital, Chinese Academy of Medical Sciences (CAMS) were retrospectively analyzed. All patients were pretreated with anthracyclines and at least one taxane in neo-adjuvant, adjuvant or chemotherapy for mTNBC and patients should be having at least one measurable metastatic lesion. Totally, 48 patients were included in this study, of which 21 cases received first-line chemotherapy and 27 cases received second-line chemotherapy. Based on the regimen they received, 22 patients were treated with NVB plus platinum (NP), and 26 patients with NVB plus capecitabine (NX). After 70 months follow-up, in the total group of patients, the objective response rate was 20.8%, clinical benefit rate was 43.8%, median progression free survival (PFS) was 4.4 months and median overall survival (OS) was 15.5 months. In addition, the ORR was significantly better in the NP arm versus NX arm (33.8% vs.7.7%, P=0.029) as well as PFS was statistically improved in the NP arm than NX arm (5.3 m vs. 3.0 m, P=0.023). Similar trend was observed in the OS, although the difference was not statistically significant (27.7 m vs. 14.8 m, P=0.077). In all, the most frequently reported adverse events were G1/2 gastrointestinal toxicity (68.8%) and neutropenia (62.5%) . No significant difference was observed between the NP arm and NX arm (P>0.05). The percentage of patients who delayed chemotherapy administration in the NP arm and NX arm was 9.1% (n=2), and 3.8% (n=1), respectively. NVB-based combination chemotherapy demonstrates moderate efficacy in mTNBC patients pretreated with anthracyclines and one taxane with manageable toxicity. NP regimen shows potential superiority over NX regimen, and should be further verified in randomized phase III clinical trial in larger cohort.

Androgen Receptor Variant Not Predictive of Taxane Response in Prostate Cancer

The approval of next-generation androgen receptor (AR)-directed therapies, such as abiraterone and enzalutamide, reinforced the critical role of the AR

Efficacy and safety of cisplatin plus capecitabine for patients with metastatic triple negative breast cancer progressing after anthracycline and taxane treatment

To evaluate the efficacy and safety of cisplatin and capecitabine combination (XP) therapy for patients with metastatic triple negative breast cancer (TNBC) progressing after anthracycline and taxane treatment. Twenty-nine metastatic TNBC patients were prospectively enrolled to receive capecitabine (1, 000 mg/m(2) twice daily on days 1-14) and cisplatin (75 mg/m(2) on day 1) , repeated every 3 weeks. With a median of 6 cycles of XP, all 29 patients were evaluable for response, including 18 PR (62.1%), 6 SD (20.7%), 5 PD (17.2%) and no CR. The response rate was 62.1%. Patients with earlier stage at diagnosis (stage I to IIIA), longer post-operative disease free survival (>2 years) and less metastatic sites (≤ 3) obtained significantly higher response rate than patients with later stage at diagnosis (stage IIIB to IV), shorter post-operative disease free survival (≤ 2 years) and more metastatic sites (>3). The leading side effects were grade 1/2 gastrointestinal and hematological toxicities. Grade 3/4 toxicities included neutropenia (34.5%), leukocytopenia (31.0%), anemia (6.9%), thrombocytopenia (3.4%), nausea/vomiting (20.7%), stomatitis (3.4%), and hand-foot syndrome (3.4%). Cisplatin and capecitabine combination therapy is an active and well-tolerated doublet treatment in metastatic TNBC patients progressing after anthracycline and taxane treatments.

Three Chemotherapy Drugs Not Better Than Two for Gastric Cancer

Chemotherapy in advanced gastric cancer achieves response rates of less than 30% to 40% and a median survival of less than 1 year. Standard regimens combining a platinum agent and a fluorinated pyrimidine with or without a third agent (epirubicin or a taxane) have significant toxicities. But whether the use of two or three cytotoxic agents is …

306P - Outcome and Prognostic Factors in Node-Negative, Early Breast Cancer Patients Receiving Adjuvant Fec Regimen: Who Might Be Candidate for Taxanes?

ABSTRACT Aim: Anthracycline-based adjuvant chemotherapy (CT) improves overall survival (OS) in operable breast cancer (BC) patients (pts). Additional benefits are provided by taxanes (TX) in node-positive pts, but no advantage in term of OS has been demonstrated in node-negative (NN) pts. We analyzed a large institutional population of NNBC pts receiving adjuvant FEC regimen with the following objectives: 1) to describe disease-free survival (DFS) and OS; 2) to identify poor-prognostic factors that may help to select high-risk pts who might be candidate to TX. Methods: Between 1998 and 2008, 757 NNBC pts receiving adjuvant FEC (5FU 500 mg/m2, Epirubicin 75 or 100 mg/m2, cyclophosphamide 500 mg/m2) were identified from our institutional database. Features indicating adjuvant CT were pathological tumor size >15 mm, grade 3, peritumoral vascular invasion (PVI), no hormonal receptivity (ER and PR-, HR-), age Results: After a median follow-up of 70 months, 69 DFS events and 39 deaths were observed, for 5-year DFS and OS of 90.6% (CI95%, 88.2-93.1) and 95.1% (CI95%, 93.3-96.9), respectively. Univariate analysis identified PVI (p = 0.0007), grade 3 (p = 0.0138), PR-negative (p = 0.0293) and molecular subtypes (p = 0.0003) as prognostic factors for DFS. No significant prognostic impact was observed for HER2+ BC. By multivariate analysis, PVI and grade 3 maintained a significant and independent prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, luminal B-like (HR = 4.21, CI95%, 1.955-9.055, p = 0.0002) and basal-like (HR = 2.54, CI95%, 1.173-5.497, p = 0.018) subtypes were significantly associated with reduced DFS. Conclusions: Overall, NNBC pts receiving adjuvant FEC have excellent 5-year DFS and OS. PVI, luminal B-like and basal-like subtypes identify pts with a higher risk of treatment failure, who might be candidate to TX. Disclosure: All authors have declared no conflicts of interest.

Chemotherapy and molecular targeted therapy of advanced gastric cancer

Chemotherapy and molecular targeted therapy are the main treatments in unresectable gastric cancer. In recent years,due to the adjustment and optimization of chemotherapy regimens which are consist of fluorouracil,platinum and taxane,the survival time of gastric cancer patient has been prolonged and the quality of life has been improved. The molecular targeted therapy in gastric cancer arouses more and more concern,and there are many phrase Ⅲ clinical trials which are used to assess the efficacy of molecular targeted therapy. The advances of chemotherapy and molecular targeted therapy bring new hope to advanced gastric cancer patients. Key words: Stomach neoplasms; Drug Therapy; Molecular targeted therapy

Efficacy of domestic gemcitabine combined with Lobaplatine in salvage treatment of taxanes-refractory advanced lung squamous carcinoma

Objective To evaluate the effiacy and adverse reactions of domestic gemcitabine combined with lobaplatine in salvage treatment of taxanes-refractory advanced lung squamous canceroma.Methods 71 patients with squamous carcinoma of lung,all had been failer to combined chemotherapy with taxanes treatment before,received the treatment with domestic gemcitabine (1 000mg/m2,d1,8) combined with lobaplatine (30mg/m2,d2),21-28 days as a cycle,at least 2 cycles should been recieved.The therapeutic efficacy was evaluated after 2 cycles of chemotherapy,according to RECIST1.0 standard.Results All of 175 cycles had been observed.In terms of the treatment efficacy,68 patients could be evaluated objectively of 71 cases patients,partial response (PR) was 15 cases (22.0％),stable disease(SD) was 18 cases(26.4％),with an overall response rate(RR) was 22.0％ (15/68),disease control rate (DCR) was 48.5 ％ (33/68).The median time to progression (TTP) was 13.6 weeks.the median survival time (OS) was 7.9 months.One year survival rate was 42.6％ (29/68).On 71 cases for a total of 175 cycles of chemotherapy,the major toxic reaction was hematological toxicities,including myelosuppression about 38.3％ (67/175) for grade Ⅲ and Ⅳ.Conclusion The combination treatment of domestic gemcitabine plus lobaplatin is a feasible and active scheme in salvage treatment of taxanes-refractory advanced quamous carcinoma of lung. Key words: Carcinoma, non-small-cell lung; Antineoplastic combined chemotherapy protocols ; Drug resistance, neoplasm

Prospective evaluation of echocardiography and serum biomarkers as predictors of cardiotoxicity in patients with breast cancer treated with anthracyclines, taxanes, with/without trastuzumab.

e20686 Background: To evaluate whether echocardiographic parameters and serum biomarkers may predict early cardiac dysfunction in patients treated with taxanes, anthracyclines with / without trastu...

Treatment and prognosis of 117 patients with advanced urothelial carcinoma of the bladder

The aim of this study was to analyze the clinical characteristics, treatment and prognosis of advanced urothelial carcinoma of the bladder (AUCB). The clinicopathological data of 117 patients with AUCB admitted in our hospital from 1998 to 2009 were reviewed. All patients received first-line chemotherapy. The survival rate was calculated by Kaplan-Meier analysis and log-rank test. The median age of all patients was 56 years and the male-to-female ratio was 3.33:1. Their 6-, 12-, 24-, 36- and 60-month survival rates were 90.3%, 61.3%, 32.3%, 24.2% and 8.1%, respectively. In the first-line chemotherapy regimen, the effectiveness rate of gemcitabine + platinum drugs was 49.3% (37/75), the median progression-free survival(PFS) was 7.9 months and overall survival (OS) was 18.7 months. The effectiveness of cyclophosphamide + epirubicin + platinum drug regimen was 45.5% (10/22), Median PFS was 7.1 months and OS was 15.3 months. The effectiveness of paclitaxel + platinum drug regimen was 47.1% (8/17), median PFS was 6.5 months and OS was 13.7 months. Among them, the effectiveness rate of the gemcitabine + cisplatin regimen in 67 patients was 47.8%, the median PFS was 7.0 months and OS was 15.3 months. In the 13 patients who received paclitaxel + carboplatin regimen, the effectiveness rate was 53.8%, median PFS was 7.7 months and OS was 16.0 months. The major side effects were leucopenia and thrombocytopenia, mostly were tolerable, of grade I to II. In advanced unresectable and metastatic urothelial carcinoma of the bladder, GC regimen is recognized as a standard first-line chemotherapy, with a higher effectiveness and tolerable side effects. Taxane and molecular targeted drugs may further improve the therapeutic effect of the treatment of advanced urothelial carcinomas of the bladder in the future.

Everolimus Fails to Improve Survival in Refractory Gastric Cancer

Median survival with first-line chemotherapy for metastatic gastric cancer is less than 1 year, and second-line chemotherapy with taxanes or irinotecan confers only a modest survival benefit. Trastuzumab, which targets the human epidermal growth factor receptor 2 (HER2), is the only targeted therapy approved for gastric cancer, but it is used only in the minority of patients with HER2-positive disease. Another potential target that appears to be activated in gastric cancer is the PI3 kinase/AKT/mTOR pathway, …

Phase Ib study of eribulin (ERB) and cyclophosphamide (CTX) in metastatic breast cancer (MBC).

153 Background: ERB is a non-taxane microtubule inhibitor approved for the treatment (Tx) of taxane (TAX) and anthracycline-treated MBC based on improved OS compared to treatment of physician choice. In the adjuvant setting, docetaxel/CTX (TC) was superior to doxorubicin/CTX for DFS and OS. ERB is active in TAX-resistant disease with a low rate of peripheral neuropathy (PN); its primary dose-limiting toxicity (DLT) is bone marrow suppression. We hypothesized that the combination of ERB and CTX would be well tolerated and active in patients with TAX-resistant disease, with potential applicability to the adjuvant setting. Methods: We designed a 3+3 phase Ib study of ERB, administered in 2 escalating doses on day 1 and 8, with CTX 600 mg/m2day 1 every 21 days. Eligibility included PN ≤ grade 1. Correlative studies to identify predictors of response and toxicity included whole blood for SNPs, GWAS, circulating tumor cells (CTC), and archived tumor RNA/protein expression analysis. Toxicity assessment included QoL and evaluation of PN. Results: 6 patients (pts) with MBC, median age 50 (47-63), were enrolled. All pts had prior TAX exposure and 4 pts had baseline grade 1 PN. Tumor characteristics included hormone receptor + (5 pts), HER2+ (2 pts), and triple-negative (1 pt). Median number of prior Tx for MBC was 5 (1-8). No DLTs were observed; the RP2D is eribulin 1.4 mg/m2 on D1 and D8 with CTX D1 600mg/m2. Neutropenia was the only G3/G4 non-DLT observed at this dose, requiring GCSF support in cycle 1 in 2 of 3 pts. All grade toxicities included neutropenia (50%), thrombocytopenia, fatigue, nausea, PN, rash, mucositis, alopecia (33% each), and elevated liver enzymes (17%). Pts received a median of 5.5 cycles (range 3-13), with 3 pts still on Tx. Responses included 2PRs (33%) and 4 SD (67%). 2 pts stopped study Tx for QoL and continued ERB alone. Only 2 pts met threshold of &gt;5CTC/7.5ml at baseline; these had a mean decrease of 90.5% at the start of cycle 2. Conclusions: ERB and CTX is a well-tolerated regimen with promising activity in MBC, with the primary toxicity being neutropenia requiring growth factor support. A phase II study in MBC is underway. Additional correlative studies are ongoing, including molecular analyses of CTC. Clinical trial information: NCT01554371.

Effects of Vinorelbine Combined with Xeloda in Anthracycline- and Taxane-pretreated Patients with Relapsed Metastatic Breast Cancer

Objective To evaluate the short-term efficacy and adverse reactions of vinorelbine combined with xeloda to patients with recurrent and metastatic breast cancer after taxane and anthracycline treatment.Methods Forty patients with recurrent metastatic breast cancer after taxane and anthracycline treatment were recruited.Vinorelbine 25 mg/m2 on day 1 and day 8,capecitabine 1 000 mg/m2,twice daily on day 1 to 14.Three weeks was one cycle.At least two cycles were given to each patient.Results Of the 40 patients,3 achieved CR,17 achieved PR,16 achieved SD,4 achieved PD,with a total response rate of 47.5%,with a clinical benefit response 70%.The median time to disease progression was 8.5 months.The common adverse reactions were myelosuppression,gastrointestinal reactions,hand-foot syndrome and neurotoxicity.Conclusion vinorelbine combined with capecitabine is an effective rigmens in the treatment of patients with relapsed and metastatic breast cancer,especially for those who have failed in chemotherapy with taxane and anthracycline.The therapy is well tolerated but has mild adverse reactions.