scholarly journals Phase 1/2 Study of Topical Submicron Particle Paclitaxel for Cutaneous Metastases of Breast Cancer

2021 ◽  
Author(s):  
Mario E. Lacouture ◽  
Shari B. Goldfarb ◽  
Alina Markova ◽  
Sant P. Chawla ◽  
Karan V. Dewnani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Controlled Trial ◽  
Phase 1 ◽  
Progression Free Survival ◽  
Complete Response ◽  
Systemic Absorption ◽  
Breast Cancer Patients ◽  
Submicron Particle ◽  
Cutaneous Metastases ◽  
Ointment Base

Abstract Purpose: This Phase 1/2 study evaluated safety and efficacy of a topical submicron particle paclitaxel (SPP) in an anhydrous ointment base (SOR007), primarily in breast cancer patients with cutaneous metastases (CM).Methods: One of 3 concentrations of SOR007 SPP (0.15%, 1.0%, or 2.0%) was applied twice daily over an area of 50 cm2 under a 3+3 phase I design for up to 28 days, with the option for additional 28 days at the highest dose once safety was established. Efficacy was analyzed by lesion measurements and photographs to determine overall response rate (ORR), complete response (CR) and progression free survival by day 28 or 56.Results: Twenty-three subjects were enrolled, 21 with cutaneous metastases of breast cancer (CMOBC). Four subjects received SOR007 0.15%, three at a dose of 1.0% for a median of 28 days (range = 6 to 29 days), and sixteen at 2.0% for a median of 56 days (range = 42 to 60). All doses were well tolerated, and 19 subjects were evaluable for efficacy. At day 28 across all dose levels, 16% (95%CI: 3.4 to 39.6%) of subjects achieved an ORR and another 63.1% (95%CI: 34.9 to 96.8%) had stable disease (SD). The proportion of patients being progression free at 28 days across all treatments was 79% (95:CI: 54 to 94%). Conclusion: Application of SOR007 0.15%, 1.0%, and 2.0% to CM resulted in lesion stabilization or response in most subjects, with reduced lesion pain, and minimal systemic absorption of paclitaxel. A randomized, placebo-controlled trial to confirm these findings is warranted.NCT: #03101358

scholarly journals Efficacy and Safety of Eribulin in Taxane-Refractory Patients in the “Real World”

2016 ◽  
Author(s):  
Vito Lorusso ◽  
Saverio Cinieri ◽  
Agnese Latorre ◽  
Luca Porcu ◽  
Lucia Del Mastro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Peripheral Neurotoxicity ◽  
Eribulin Mesylate ◽  
Free Survival ◽  
Toxic Drugs

Taxanes have been shown to be the most effective treatment for recurrent or metastatic breast cancer. However, for patients pretreated with taxanes, more active and possibly less toxic drugs are needed. In this retrospective study, we investigated on the effectiveness and safety of eribulin mesylate in 91 taxane-refractory subjects, extracted from the ESEMPIO database, which included 497 metastatic breast cancer patients treated with eribulin allover the Italy. This analysis included only those patients who have shown disease progression while receiving taxane therapy (primary refractory), or those who achieved a response followed by progression while still on therapy (taxane failure). Overall, 41/91 patients (45.2%) showed a clinical benefit; 1 complete response (2.2%) and 16 partial responses (17.6%) were observed. The median progression free survival was 3.1 months (95% CI: 2.8–3.5) and the median overall survival was 11.6 months (95% CI: 8.7–16.7). With regard to toxicity, 53 patients (58%) experienced asthenia/fatigue, 23 (25%) showed peripheral neurotoxicity, 18 (20%) alopecia, 12 (13%) mild constipation and 27 (30%) neutropenia. The toxicity related to the treatment led to eribulin dose reduction in 19 (21%) and discontinuation in 9 (10%) patients, respectively. In conclusion, this study suggests that eribulin is effective and well tolerated also in taxane-refractory patient.

Activity of eribulin on skin metastases in breast cancer patients.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12021-e12021
Author(s):  
Nicla Maria La Verde ◽  
Anna Moretti ◽  
Teresa Gamucci ◽  
Karen Borgonovo ◽  
Mario Botta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Performance Status ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Skin Metastases ◽  
Multicenter Survey ◽  
Skin Response ◽  
Metastatic Sites

e12021 Background: Skin metastases (SM) occur in 20% of metastatic breast cancer (mBC). Clinical trials rarely describe them, even if they affect quality of life and self-perception of the disease. Eribulin (E) is a new drug, approved in mBC, after at least 2 lines of chemotherapy. The aim of this survey is to evaluate the activity of E treatment on SM compared to other metastatic sites, and on cutaneous symptoms (pain, infiltration, bleeding, smell, ulceration). Methods: This multicenter survey was conducted from November 2012 to January 2013 in 14 Italian Cancer Centers. Oncologists completed a database with patient (pts), tumor and treatment characteristics. Descriptive summary statistics were applied. Progression-free survival (PFS) was calculated according to Kaplan-Meier method. Results: 109 pts with mBC on E treatment were considered. 23/109 (21%) pts with SM were identified and analyzed. E was started between January 2012 and October 2012. Median age 63 (31-81). Prior chemotherapy lines: 4 (1-10). Prior hormonal lines: 1 (0-4). Basal Karnofski performance status 90 (50-100). 21/23 pts had other metastases, the remaining 2 had exclusively skin disease. SM were predominantly in the thorax (91%) and presented infiltration in 78%, ulceration in 70%, pain in 43%, bleeding in 43% and smell in 17% of cases. According to RECIST criteria, after E 43% of patients obtained a partial response (PR), 35% stable disease (SD), 22% progressive disease (PD). We evaluated skin response independently and found that 26% obtained a complete response (CR); 22% PR, 39% SD, 13% PD. Skin responses were in complete accordance with overall response in 16/23 (70%) pts, in partial accordance in 4 pts (skin CR, with an overall PR) and were discordant in 3 pts (1 skin SD despite overall PR, and 2 cutaneous CR despite overall PD). We found an improvement in SM symptoms: pain control was gained in 50% (5/10) of pts, as well as improvement in smell (50%, 2/4) and bleeding (50%, 5/10). Infiltration disappeared in 3/18 pts (17%). With a median follow up of 6 months, 21 (91%) pts had PD, median PFS was 4.3 months (95%CI 2.9–6). Conclusions: During E an improvement in skin metastases symptoms was observed; in the majority of cases, the response rate of SM was coherent with systemic responses.

scholarly journals Association of PTP1B with Outcomes of Breast Cancer Patients who Underwent Neoadjuvant Chemotherapy

2016 ◽  
Vol 10 ◽  
pp. BCBCR.S40934 ◽  
Author(s):  
Monica M. Rivera Franco ◽  
Eucario Leon Rodriguez ◽  
Braulio Martinez Benitez ◽  
Luisa G. Villanueva Rodriguez ◽  
Maria De La Luz Sevilla Gonzalez ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Progression Free Survival ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Limited Sample ◽  
Free Survival ◽  
Epidermal Growth

PTP1B is involved in the oncogenesis of breast cancer. In addition, neoadjuvant therapy has been widely used in breast cancer; thus, a measurement to assess survival improvement could be pathological complete response (pCR). Our objective was to associate PTP1B overexpression with outcomes of breast cancer patients who underwent neoadjuvant chemotherapy. Forty-six specimens were included. Diagnostic biopsies were immunostained using anti-PTP1B antibody. Expression was categorized as negative (<5%) and overexpression (≥5%). Patients' responses were graded according to the Miller-Payne system. Sixty-three percent of patients overexpressed PTP1B. There was no significant association between PTP1B overexpression and pCR (P = 0.2). However, when associated with intrinsic subtypes, overexpression was higher in human epidermal growth factor receptor 2-positive-enriched specimens (P = 0.02). Ten-year progression-free survival showed no differences. Our preliminary results do not show an association between PTP1B overexpression and pCR; however, given the limited sample and heterogeneous treatment in our cohort, this hypothesis cannot be excluded.

Barriers to Supervised Exercise Training in a Randomized Controlled Trial of Breast Cancer Patients Receiving Chemotherapy

2008 ◽  
Vol 35 (1) ◽  
pp. 116-122 ◽  
Author(s):  
Kerry S. Courneya ◽  
Donald C. McKenzie ◽  
Robert D. Reid ◽  
John R. Mackey ◽  
Karen Gelmon ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Controlled Trial ◽  
Exercise Training ◽  
Cancer Patients ◽  
Controlled Trial ◽  
Breast Cancer Patients ◽  
Randomized Controlled ◽  
Supervised Exercise

scholarly journals Cost-effectiveness of paclitaxel, doxorubicin, cyclophosphamide and trastuzumab versus docetaxel, cisplatin and trastuzumab in new adjuvant therapy of breast cancer in china

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Qiaoping Xu ◽  
Li Yuanyuan ◽  
Zhu Jiejing ◽  
Liu Jian ◽  
Li Qingyu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cost Effectiveness ◽  
Partial Response ◽  
Cancer Patients ◽  
Transition Probabilities ◽  
Complete Response ◽  
Sensitivity Analyses ◽  
Half Cycle ◽  
Breast Cancer Patients ◽  
Grade 3

Abstract Background Breast cancer is the most common cancer among women in China. Amplification of the Human epidermal growth factor receptor type 2 (HER2) gene is present and overexpressed in 18–20% of breast cancers and historically has been associated with inferior disease-related outcomes. There has been increasing interest in de-escalation of therapy for low-risk disease. This study analyzes the cost-effectiveness of Doxorubicin/ Cyclophosphamide/ Paclitaxel/ Trastuzumab (AC-TH) and Docetaxel/Carboplatin/Trastuzumab(TCH) from payer perspective over a 5 year time horizon. Methods A half-cycle corrected Markov model was built to simulate the process of breast cancer events and death occurred in both AC-TH and TCH armed patients. Cost data came from studies based on a Chinese hospital. One-way sensitivity analyses as well as second-order Monte Carlo and probabilistic sensitivity analyses were performed.The transition probabilities and utilities were extracted from published literature, and deterministic sensitivity analyses were conducted. Results We identified 41 breast cancer patients at Hangzhou First People’s Hospital, among whom 15 (60%) had a partial response for AC-TH treatment and 13 (81.25%) had a partial response for TCH treatment.No cardiac toxicity was observed. Hematologic grade 3 or 4 toxicities were observed in 1 of 28 patients.Nonhematologic grade 3 or 4 toxicities with a reverse pattern were observed in 6 of 29 patients. The mean QALY gain per patient compared with TCH was 0.25 with AC-TH, while the incremental costs were $US13,142. The incremental cost-effectiveness ratio (ICER) of AC-TH versus TCH was $US 52,565 per QALY gained. Conclusions This study concluded that TCH neoadjuvant chemotherapy was feasible and active in HER2-overexpressing breast cancer patients in terms of the pathological complete response, complete response, and partial response rates and manageable toxicities.

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

2021 ◽  
pp. 1-9
Author(s):  
Ankita Gupta ◽  
Budhi Singh Yadav ◽  
Nagarjun Ballari ◽  
Namrata Das ◽  
Ngangom Robert
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Progression Free Survival ◽  
Rank Test ◽  
Karnofsky Performance Score ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

scholarly journals Mapping of Genomic Vulnerabilities in the Post-Translational Ubiquitination, SUMOylation and Neddylation Machinery in Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 833
Author(s):  
Jesús Fuentes-Antrás ◽  
Ana Lucía Alcaraz-Sanabria ◽  
Esther Cabañas Morafraile ◽  
María del Mar Noblejas-López ◽  
Eva María Galán-Moya ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Drug Development ◽  
Gene Mutations ◽  
Complete Response ◽  
Breast Cancer Patients ◽  
Clinical Value ◽  
Luminal A ◽  
Genomic Alterations ◽  
Cancer Hallmarks ◽  
Worse Prognosis

The dysregulation of post-translational modifications (PTM) transversally impacts cancer hallmarks and constitutes an appealing vulnerability for drug development. In breast cancer there is growing preclinical evidence of the role of ubiquitin and ubiquitin-like SUMO and Nedd8 peptide conjugation to the proteome in tumorigenesis and drug resistance, particularly through their interplay with estrogen receptor signaling and DNA repair. Herein we explored genomic alterations in these processes using RNA-seq and mutation data from TCGA and METABRIC datasets, and analyzed them using a bioinformatic pipeline in search of those with prognostic and predictive capability which could qualify as subjects of drug research. Amplification of UBE2T, UBE2C, and BIRC5 conferred a worse prognosis in luminal A/B and basal-like tumors, luminal A/B tumors, and luminal A tumors, respectively. Higher UBE2T expression levels were predictive of a lower rate of pathological complete response in triple negative breast cancer patients following neoadjuvant chemotherapy, whereas UBE2C and BIRC5 expression was higher in luminal A patients with tumor relapse within 5 years of endocrine therapy or chemotherapy. The transcriptomic signatures of USP9X and USP7 gene mutations also conferred worse prognosis in luminal A, HER2-enriched, and basal-like tumors, and in luminal A tumors, respectively. In conclusion, we identified and characterized the clinical value of a group of genomic alterations in ubiquitination, SUMOylation, and neddylation enzymes, with potential for drug development in breast cancer.

Phase III Study of Intravenous Vinorelbine in Combination With Epirubicin Versus Epirubicin Alone in Patients With Advanced Breast Cancer: A Scandinavian Breast Group Trial (SBG9403)

2004 ◽  
Vol 22 (12) ◽  
pp. 2313-2320 ◽  
Author(s):  
Bent Ejlertsen ◽  
Henning T. Mouridsen ◽  
Sven T. Langkjer ◽  
Jorn Andersen ◽  
Johanna Sjöström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Response Rate ◽  
Complete Response Rate ◽  
Metastatic Breast ◽  
Progression Free Survival ◽  
Complete Response ◽  
Phase Iii ◽  
Severe Toxicity ◽  
Free Survival

Purpose To determine whether the addition of intravenous (IV) vinorelbine to epirubicin increased the progression-free survival in first-line treatment of metastatic breast cancer. Patients and Methods A total of 387 patients were randomly assigned to receive IV epirubicin 90 mg/m2 on day 1 and vinorelbine 25 mg/m2 on days 1 and 8, or epirubicin 90 mg/m2 IV on day 1. Both regimens were given every 3 weeks for a maximum of 1 year but discontinued prematurely in the event of progressive disease or severe toxicity. In addition, epirubicin was discontinued at a cumulative dose of 1,000 mg/m2 (950 mg/m2 from June 1999). Prior anthracycline-based adjuvant chemotherapy and prior chemotherapy for metastatic breast cancer was not allowed. Reported results were all based on intent-to-treat analyses. Results Overall response rates to vinorelbine and epirubicin, and epirubicin alone, were 50% and 42%, respectively (P = .15). The complete response rate was significantly superior in the combination arm (17% v 10%; P = .048) as was median duration of progression-free survival (10.1 months v 8.2 months; P = .019). Median survival was similar in the two arms (19.1 months v 18.0 months; P = .50). Leukopenia related complications, stomatitis, and peripheral neuropathy were more common in the combination arm. The incidences of cardiotoxicity and constipation were similar in both arms. Conclusion Addition of vinorelbine to epirubicin conferred a significant advantage in terms of complete response rate and progression-free survival, but not in terms of survival.

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