taxane and Liver-Neoplasms

Breast cancer consists of a heterogeneous group of diseases, with a number of tumor-specific and patient-specific factors, which influence response to therapy and survival. Ixabepilone is a member of a novel class of antineoplastic agents, the epothilones, that has demonstrated activity in a number of human solid tumor types and is the first agent in this class to be approved by the Food and Drug Administration (FDA) for the treatment of metastatic or locally advanced breast cancer, that is resistant/refractory to anthracyclines, taxanes, and/or capecitabine. Both retrospective and prospective studies have been conducted to evaluate the efficacy of ixabepilone in various populations. The role of ixabepilone in poor prognosis subgroups of the metastatic breast cancer population is reviewed in this article.

Topics: Adult; Aged; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Clinical Trials, Phase III as Topic; Drug Approval; Drug Delivery Systems; Drug Resistance, Neoplasm; Epothilones; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Neoplasm Invasiveness; Neoplasm Staging; Patient Selection; Prognosis; Randomized Controlled Trials as Topic; Survival Analysis; Taxoids; Treatment Outcome; United States; United States Food and Drug Administration

First-line bevacizumab combined with chemotherapy significantly improves efficacy versus chemotherapy alone in human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer (LR/mBC). This large, open-label study further assesses first-line bevacizumab with taxane-based chemotherapy in routine oncology practice.. Patients with HER2-negative LR/mBC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of zero to two and no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks plus taxane-based chemotherapy (or other non-anthracycline chemotherapy) until disease progression, unacceptable toxicity or patient withdrawal. The primary end point was safety; time to progression (TtP) was a secondary end point.. Median follow-up in 2251 treated patients was 12.7 months. Median age was 53 years and 94% of patients had ECOG PS of zero or one. Bevacizumab was most commonly administered with single-agent paclitaxel (35%), single-agent docetaxel (33%) or taxane-based combination therapy (10%). The most frequent grade ≥3 adverse event (AE) was neutropenia (5.4%). Grade ≥3 AEs previously associated with bevacizumab included hypertension (4.4%), arterial/venous thromboembolism (3.2%), proteinuria (1.7%) and bleeding (1.4%). No new bevacizumab safety signals were observed. Median TtP was 9.5 months (95% confidence interval 9.1-9.9).. The study population in ATHENA was more representative of general oncology practice than populations enrolled into randomised trials, although there may have been some bias towards younger, fitter patients. The safety and efficacy of bevacizumab-taxane therapy in this large study were consistent with results from randomised first-line trials.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Bone Neoplasms; Brain Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Lung Neoplasms; Male; Middle Aged; Neoplasm Recurrence, Local; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Taxoids; Treatment Outcome; Young Adult

This study was designed to evaluate the efficacy and safety of single-agent gemcitabine for the treatment of patients with anthracycline- and taxane-pretreated metastatic breast cancer (MBC). Eligible patients were required to have bidimensionally measurable MBC that had been treated with 2-4 prior chemotherapy regimens that included an anthracycline and a taxane. Gemcitabine was delivered at a dose of 800 mg/m2 on days 1, 8, and 15 of a 28-day cycle until evidence of disease progression.. Twenty-two patients were enrolled and included in the safety analysis; 18 patients were evaluable for response. The median age of patients was 54 years (range, 36-70 years). The mean number of prior chemotherapy regimens for metastatic disease was 2.3, and the mean dose of gemcitabine delivered was 911 mg/m2 (range, 600-1600 mg/m2).. Overall, gemcitabine was well tolerated with minimal grade 3 toxicities; the only grade 4 toxicity was 1 case of pulmonary embolus. Three patients had evidence of partial tumor regression (17%; 95% CI, 4%-41%), and 1 patient had a 41% decrease in tumor volume, including liver metastasis.. Gemcitabine is active and well tolerated as monotherapy given in heavily pretreated patients with MBC after anthracyclines and taxanes. The activity and safety reported in this trial are consistent with previous reports in similar patients.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Deoxycytidine; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Female; Gemcitabine; Humans; Infusions, Intravenous; Liver Neoplasms; Lung Neoplasms; Middle Aged; Nausea; Neoadjuvant Therapy; Neoplasm Staging; Prognosis; Salvage Therapy; Skin Neoplasms; Soft Tissue Neoplasms; Survival Analysis; Taxoids; Treatment Outcome; Vomiting

The purpose of this study was to determine the maximum tolerated dose (MTD) of infusional gemcitabine given in conjunction with intravenous (i.v.) cyclophosphamide, and to determine whether the regimen produced a response rate of at least 40% in patients with metastatic breast cancer who have been previously treated with taxanes. Patients received cyclophosphamide (600 mg/m2) i.v. followed immediately by gemcitabine (100, 150, or 200 mg/m2) given as a 24-hour infusion (every 3 weeks) using an accelerated dose-escalation schema. Dose-limiting toxicity was defined as a neutrophil nadir < 500/microL, platelet nadir < 50,000/microL, or > or = grade 2 nonhematologic toxicity (> or = grade 3 toxicity during the standard dose-escalation portion of the study). Twelve patients received a total of 32 cycles of therapy. The MTD of gemcitabine was 150 mg/m2. Dose-limiting toxicities at 200 mg/m2 included neutropenia and mucositis. One patient with lymphangitic lung metastases had a partial response (8%; 95% confidence intervals: 0%, 23%). This patient developed grade 4 transaminase and total bilirubin elevation that occurred after the sixth cycle of therapy. The study was terminated due to an insufficient number of responses. The MTD of gemcitabine given as a 24-hour infusion is 150 mg/m2 when used in conjunction with cyclophosphamide (600 mg/m2) every 3 weeks. This regimen is not likely to produce more than a 40% response rate in patients with metastatic breast cancer previously treated with taxanes.

Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Agents, Alkylating; Antineoplastic Combined Chemotherapy Protocols; Aspartate Aminotransferases; Bilirubin; Bone Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Cyclophosphamide; Deoxycytidine; Dose-Response Relationship, Drug; Female; Gemcitabine; Humans; Infusions, Intravenous; Liver Neoplasms; Lung Neoplasms; Middle Aged; Survival Analysis; Taxoids; Treatment Outcome

Impact of second-line chemotherapy in unresectable advanced/recurrent gastric/esophagogastric junction cancer (AGC) remains unclear. This retrospective analysis aimed to identify factors affecting prognosis in chemotherapy for patients with AGC, including the importance of progression-free survival in second-line chemotherapy (PFS-2).. Data from a total of 109 patients with AGC that received second-line treatment were analyzed with the aim of clarifying prognostic factors. Furthermore, the correlation between PFS-2 and clinical characteristics and the association between PFS-2 and inflammation-based and/or nutritional markers were investigated.. Multivariate analysis identified the following prognostic factors: ECOG PS ≥1, presence of peritoneal dissemination, metastasis in two or more organs, and taxane use on second-line chemotherapy. Short PFS-2 was strongly associated with prognosis in the univariate analysis [hazard ratio (HR)=3.107, 95% confidence interval (CI)=1.969-4.904, p<0.001]. The duration of PFS-2 was significantly correlated with ECOG PS (p=0.019), liver metastasis rates (p=0.035) and taxane use on second-line chemotherapy (p=0.001). In addition, weight loss rate during first-line treatment (p=0.042), white blood cell count (p=0.008), C-reactive protein (p=0.032), c-reactive protein to albumin ratio (p=0.039), prognostic index (p=0.028), and modified Glasgow prognostic score (p=0.027) were significantly associated with the duration of PFS-2.. The duration of PFS-2 significantly correlated with ECOG PS, liver metastasis, and taxane use on second-line treatment, and strongly affected OS. It was suggested that the presence of malnutrition and inflammation at the start of second-line therapy had a negative impact on PFS-2 and OS.

Topics: C-Reactive Protein; Humans; Inflammation; Liver Neoplasms; Progression-Free Survival; Retrospective Studies; Stomach Neoplasms; Taxoids

This study proposed a conception of individualized chemotherapy based on organ selectivity of drug distribution by retrospectively comparing the effect of vinorelbine and capecitabine in patients with metastatic breast cancer.. Between January 2002 and December 2009, 133 patients with lung metastasis and 87 patients with liver metastasis were analyzed and followed up until December 2012. The survival analysis was performed by Kaplan-Meier. Multivariate analysis was conducted to identify independent prognostic factors.. The median time to progression of the vinorelbine, capecitabine and anthracycline/taxane groups of patients with lung metastasis was 5.7, 2.9 and 2.1 months, respectively. Median overall survival of the vinorelbine group (27.4 months) was longer than the capecitabine (12.2 months, P = 0.027) and anthracycline/taxane groups (9.1 months, P < 0.001) in patients with lung metastasis. The median time to progression of the vinorelbine, capecitabine and anthracycline/taxane groups of patients with liver metastasis was 2.3, 7.3 and 2.6 months, respectively. Median overall survival of the capecitabine group (15.2 months) was longer than the vinorelbine (9.0 months, P = 0.029) and anthracycline/taxane groups (6.4 months, P = 0.004) in patients with liver metastasis.. Our results indicate that vinorelbine and capecitabine have different advantageous effects in breast cancer patients with lung/liver metastasis. Thus, we propose individualized chemotherapy based on organ specificity and pharmacokinetics.

Topics: Adult; Aged; Anthracyclines; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Deoxycytidine; Female; Fluorouracil; Humans; Kaplan-Meier Estimate; Liver Neoplasms; Lung Neoplasms; Middle Aged; Organoplatinum Compounds; Precision Medicine; Retrospective Studies; Taxoids; Vinblastine; Vinorelbine

It is not clear what the optimal treatment of chemotherapy is for patients with heavily treated metastatic breast cancer (MBC). We have retrospectively examined the efficacy and safety of S-1 in patients with MBC who had been previously treated with anthracycline, taxane, and capecitabine.. Patients with MBC who had been administered S-1, an oral modulated compound containing a fluoropyrimidine derivative, between November 2001 and June 2003 at the Cancer Institute Hospital were retrospectively reviewed. S-1 at a standard dose of 50 mg/body was administered twice daily for four weeks, followed by a two-week rest period. This was repeated every six weeks until disease progression or unacceptable toxicity.. Thirty-five patients were assessed. The patients were heavily pretreated with anthracycline (100%), taxane (paclitaxel or docetaxel) (100%), capecitabine (100%), vinorelbine (71%), and mitomycin (69%). Median follow-up time of patients was 9.6 months (range, 1.2-26.6). ORR was 3% (95% confidence interval: 0-9%), and CBR was 20% (95% confidence interval: 6-33%). Time to treatment failure was 2.8 months. Overall survival was 21.4 months. Grade 1 or 2 adverse events were observed in 17% and 13%, respectively. Grade 3 events occurred as anorexia (9%), nausea (9%), vomiting (9%), diarrhea (14%), fatigue (3%), and elevation of AST/ALT (3%). No grade 3 was seen as hand-foot syndrome. Neither grade 3 nor 4 was observed in bone marrow suppression.. S-1 was fairly well tolerated, but demonstrated very limited activity in capecitabine-pretreated patients who had already been exposed to anthracycline and taxane. It was suggested that S-1 clinically exhibited cross-resistance to capecitabine.

Topics: Adult; Aged; Aged, 80 and over; Anthracyclines; Antimetabolites, Antineoplastic; Bone Neoplasms; Breast Neoplasms; Bridged-Ring Compounds; Capecitabine; Deoxycytidine; Drug Combinations; Drug Resistance, Neoplasm; Female; Fluorouracil; Humans; Liver Neoplasms; Lung Neoplasms; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Oxonic Acid; Pleural Neoplasms; Prognosis; Retrospective Studies; Survival Rate; Taxoids; Tegafur; Treatment Outcome

Of 231 patients with recurrent or metastatic breast cancer treated in Hiei Hospital between January 2001 and March 2005, for whom data on hormone receptor (HR) and HER 2/neu were available, we retrospectively analyzed the association of the response rate with HR and HER 2 in 172 patients treated with taxane in whom the treatment response could be evaluated. Among the patients treated with taxane alone,the response rates were 37.5% (n=67) in the HR (+) patients and 14.6% (n=41) in the HR (-) patients (p=0.0131). In particular, taxane resistance was suggested in the HR (-)/HER 2 (-) patients (response rate: 4.2%, n=24). Concerning combination therapy with trastuzumab and taxane, the response rate were 52.8% in the HR (+)/HER 2 (+) patients and 60.4% in the HR (-)/HER 2 (+) patients. In 27 of these patients, single therapy with taxane was switched to combination therapy with taxane and trastuzumab after they became resistant to taxane, and 8.3% of the HR (+)/HER 2 (+) patients and 53.3% of the HR (-)/HER 2 (+) patients responded to this combination therapy (p=0.0192), suggesting the synergistic effects of the two agents in HR (-)/HER 2 (+) patients. Therefore, HR and HER 2 were associated with the sensitivity to a chemotherapeutic agent, taxane. Stratification with respect to HR and HER 2 is important in the treatment of metastatic breast cancer. In particular, therapeutic strategies for HR (-)/HER 2 (-) patients with a poor prognosis must be established in the future.

Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Female; Humans; Liver Neoplasms; Pleural Effusion, Malignant; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Retrospective Studies; Survival Rate; Taxoids; Trastuzumab

We experienced a case of recurrent breast cancer resistant to prior medications, which was treated with oral S-1, a fluoropyrimidine-class anticancer drug, and exhibited the marked shrinkage of liver metastasis. The prior treatments including anthracycline and taxane were judged not effective because of the progressive disease. Then the oral treatment with S-1 was started at 120 mg/day bid. targeting metastatic lesions of the liver. At the end of the second cycle,a significant improvement was noted with a decrease rate of 82.5%. The S-1 monotherapy was thus considered to be an effective treatment for advanced or recurrent breast cancer resistant to anthracyclines and taxanes.

Topics: Anthracyclines; Antimetabolites, Antineoplastic; Antineoplastic Agents; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Mastectomy, Segmental; Middle Aged; Oxonic Acid; Pyridines; Taxoids; Tegafur

We had 2 patients with marked shrinkage of liver metastasis by administration of the oral fluorinated pyrimidine anticancer drug S-1 for advanced/recurrent breast cancer that was resistant to taxane and another antitumor drugs. Both patients almost completed the full dose through the whole course of treatment,and the drug showed good tolerability. S-1 was considered to possess beneficial antitumor efficacy and tolerability and to be promising as home chemotherapy for advanced/recurrent breast cancer.

Topics: Administration, Oral; Anthracyclines; Antimetabolites, Antineoplastic; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Middle Aged; Oxonic Acid; Pyridines; Taxoids; Tegafur

To analyze the clinical characteristics, efficiency of treatment and potential prognostic factors of breast cancer patients with liver metastases (BCLM).. The data of clinical characteristics, response to treatment and survival were retrospectively analyzed in 152 breast cancer patients with liver metastasis using SPSS 11.5.. The median disease free survival (DFS), the median survival of recurrence (MSR) and median time to progress (TTP) of this series was 21 months, 16 months and 7.4 months, respectively. The response rate in chemotherapy group was higher than that in the transcatheter arterial chemoembolization (TACE) group (37.7% vs. 53%, P = 0. 039). The TTP was longer (7 m vs. 10 m, P = 0.048) and the response rate (63.3% vs. 40.0%, P = 0.04) in taxanes-based chemotherapy group was significantly higher than that in non-taxanes-containing regimen. The MSR in patients with single liver metastases treated by TACE was longer than that by chemotherapy (16 m vs. 30 m, P = 0.0052), but it was not observed in the patients with multiple metastases. Pathological tumor size (PT) and axillary lymph node status at diagnosis, negative estrogen receptor (ER) status, abnormal ALT level induced by liver metastases, metastastic tumor size were significantly correlated with shorter survival.. The effective chemotherapy especially the taxane-containing regimen and TACE may improve outcome for breast cancer patient with liver metastasis.

Topics: Alanine Transaminase; Antineoplastic Agents; Breast; Breast Neoplasms; Bridged-Ring Compounds; Chemoembolization, Therapeutic; Combined Modality Therapy; Disease Progression; Disease-Free Survival; Female; Follow-Up Studies; Humans; Liver Neoplasms; Lymphatic Metastasis; Mastectomy; Middle Aged; Neoplasm Staging; Prognosis; Proportional Hazards Models; Receptors, Estrogen; Retrospective Studies; Taxoids

A 53-year-old woman presented with an advanced right breast cancer together with skin manifestations and massive axillary lymph node metastases, as well as distant metastases in the lung and the liver. The patient received surgery after 6 courses of chemotherapy with epirubicine and intravenous cyclophosphamide (80/600 mg/m2). A weekly paclitaxel regimen (80 mg/m2) was started because the tumor markers increased soon after surgery. Despite chemotherapy, no response was confirmed, then weekly docetaxel (35 mg/m2) was started. Although the tumor markers decreased after administration of docetaxel, severe liver disfunction appeared and did not improve after cessation of docetaxel. Computed tomography (CT) revealed numerous metastatic nodules in the bilateral lobes of the liver. UFT (400 mg/day) and cyclophosphamide (100 mg/day) were administered for 4 weeks followed by 2 weeks cessation and then combined with continuous medroxyprogesterone acetate (800 mg/day). Liver function tests were normalized 3 months after, and the massive metastatic liver tumors disappeared completely. Lung metastasis also subsided. In spite of these good responses, tumor markers did not normalize and skin nodules appeared around the surgical site. Administration was stopped 36 weeks after initiation of the treatment.

Topics: Adenocarcinoma, Scirrhous; Administration, Oral; Anthracyclines; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Bridged-Ring Compounds; Cyclophosphamide; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Medroxyprogesterone Acetate; Middle Aged; Taxoids; Tegafur; Uracil

A patient with lung metastasis of breast cancer was reported. The patient underwent surgery in December, 1999. Her breast cancer then recurred in December, 2000. After treatment failure with anthracycline and taxane antitumor drugs,she participated in a phase II study of S-1, a fluorinated pyrimidine anticancer drug, which was given orally at 80 mg/m2/day (2 doses). After completion of 4 courses of treatment,the target lesions of the lung metastasis markedly shrunk by 47.5% as compared with the pretreatment. Because salvage therapy with S-1 alone showed good antitumor efficacy and beneficial tolerability when the standard dosage was maintained, it was considered that this home therapy was effective for advanced/recurrent breast cancer that was resistant to anthracycline and taxane antitumor drugs.

Topics: Administration, Oral; Anthracyclines; Antimetabolites, Antineoplastic; Breast Neoplasms; Bridged-Ring Compounds; Carcinoma, Ductal, Breast; Clinical Trials, Phase II as Topic; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm; Female; Humans; Liver Neoplasms; Lung Neoplasms; Lymphatic Metastasis; Middle Aged; Oxonic Acid; Pyridines; Quality of Life; Salvage Therapy; Taxoids; Tegafur