Purpose
We hypothesized that eribulin combined with cyclophosphamide (EC) would be an effective combination with tolerable toxicity for the treatment of advanced breast cancer (ABC).
Methods
Patients ...with histologically confirmed metastatic or unresectable ABC with any number of prior lines of therapy were eligible to enroll. In the dose escalation cohort, dose level 0 was defined as eribulin 1.1 mg/m
2
and cyclophosphamide 600 mg/m
2
,
and dose level 1 was defined as eribulin 1.4 mg/m
2
and cyclophosphamide 600 mg/m
2
. Eribulin was given on days 1 and 8 and cyclophosphamide on day 1 of a 21-day cycle. In the dose expansion cohort, enrollment was expanded at dose level 1. The primary objective was clinical benefit rate (CBR), and secondary objectives were response rate (RR), duration of response (DOR), progression-free survival (PFS), and safety.
Results
No dose-limiting toxicities were identified in the dose escalation cohort (n = 6). In the dose expansion cohort, an additional 38 patients were enrolled for a total of 44 patients, including 31 patients (70.4%) with hormone receptor-positive (HR +)/HER2- disease, 12 patients (27.3%) with triple-negative breast cancer (TNBC), and 1 patient (2.3%) with HR + /HER2 + disease. Patients had a median age of 56 years (range 33–82 years), 1 prior line of hormone therapy (range 0–6), and 2 prior lines of chemotherapy (range 0–7). CBR was 79.5% (35/44; 7 partial response, 28 stable disease) and the median DOR was 16.4 weeks (range 13.8–21.1 weeks). Median PFS was 16.4 weeks (95% CI: 13.8–21.1 weeks). The most common grade 3/4 adverse event was neutropenia (47.7%, n = 21). Fourteen of 26 patients (53.8%) with circulating tumor cell (CTC) data were CTC-positive (
≥
5 CTC/7.5 mL) at baseline. Median PFS was shorter in patients who were CTC-positive vs. negative (13.1 vs 30.6 weeks, p = 0.011).
Conclusion
In heavily pretreated patients with ABC, treatment with EC resulted in an encouraging CBR of 79.5% and PFS of 16.4 weeks, which compares favorably to single-agent eribulin. Dose reduction and delays were primarily due to neutropenia. The contribution of cyclophosphamide to eribulin remains unclear but warrants further evaluation. NCT01554371.
Objective: Sunitinib is a novel oral multitargeted tyrosine kinase inhibitor with antitumor and antiangiogenic activities. This study evaluates ezrin expression in sunitinib-treated metastatic clear ...cell renal cell carcinoma (ccRCC) patients and elucidates its role as a possible marker for survival.
Materials and Methods: The expression of ezrin was measured by immunohistochemistry in 80 patients with ccRCC treated by first-line sunitinib between January 2007 and June 2012. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on the survival.
Results: In multivariate analysis, liver metastasis (P = 0.018; hazard ratio HR: 3.707 (1.257-10.931) and overexpression of ezrin (P = 0.006; HR: 2.993 (1.373-6.523 95% confidence interval) were remained significant factors influencing OS. Overexpression of ezrin in the patients who had progressed in the first 3 months was higher than in the patients who had progressed after 3 months (P = 0.003). The median OS was longer in patients with low levels of ezrin expression (27 months) compared to patients overexpressing ezrin (12 months) (P = 0.001).
Conclusion: This is the first study in the literature showing that ezrin status is related with prognosis in patients with metastatic ccRCC.
Aim
Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS).
Patients and methods
This multicenter study ...is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma LMS, undifferentiated pleomorphic sarcoma UPS, synovial sarcoma SS) in the cohort.
Results
Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively.
Conclusion
Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations.
Adrenocortical carcinoma (ACC) is a rare yet highly malignant tumor associated with significant morbidity and mortality. This study aims to delineate the clinical features, survival patterns, and ...treatment modalities of ACC, providing insights into the disease's prognosis.
A retrospective analysis of 157 ACC patients was performed to assess treatment methodologies, demographic patterns, pathological and clinical attributes, and laboratory results. The data were extracted from the hospital's database. Survival analyses were conducted using the Kaplan–Meier method, with univariate and multivariate analyses being performed through the log-rank test and Cox regression analyses.
The median age was 45, and 89.4% had symptoms at the time of diagnosis. The median tumor size was 12 cm. A total of 117 (79.6%) patients underwent surgery. A positive surgical border was detected in 26 (24.1%) patients. Adjuvant therapy was administered to 44.4% of patients. The median overall survival for the entire cohort was 44.3 months. Median OS was found to be 87.3 months (95% confidence interval CI 74.4-100.2) in stage 2, 25.8 (95% CI 6.5-45.1) months in stage 3, and 13.3 (95% CI 7.0-19.6) months in stage 4 disease. Cox regression analysis identified age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as significant factors associated with survival in patients with nonmetastatic disease. In metastatic disease, only patients who underwent surgery exhibited significantly improved overall survival in univariate analyses.
ACC is an uncommon tumor with a generally poor prognosis. Understanding the defining prognostic factors in both localized and metastatic diseases is vital. This study underscores age, Ki67 value, Eastern Cooperative Oncology Group performance status, and hormonal activity as key prognostic determinants for localized disease, offering critical insights into the complexities of ACC management and potential avenues for targeted therapeutic interventions.
Adrenocortical cancer is a rare and poor prognostic malignant tumor. The definitions of prognostic factors in localized and metastatic diseases are important. In this paper, we defined the clinical features, management, and prognostic factors related to survival in patients with metastatic and nonmetastatic ACC. Cox regression analysis showed that age, Ki67 value, ECOG PS, and hormonal activity were significantly associated with survival in patients with nonmetastatic disease. Only patients who underwent surgery had significantly better OS compared with patients without surgery in univariate analyses of metastatic disease.
Ribociclib, palbociclib and abemaciclib are currently approved CDK4/6 inhibitors along with aromatase inhibitors as the first-line standard-of-care for patients with hormone receptor-positive, ...HER2-negative metastatic breast cancer.
The authors report retrospective real-life data for 600 patients with estrogen receptor- and/or progesterone receptor-positive and HER2-negative metastatic breast cancer who were treated with ribociclib and palbociclib in combination with letrozole.
The results demonstrated that the combination of palbociclib or ribociclib with letrozole has similar progression-free survival and overall survival benefit in real life for the patient group with similar clinical features. Specifically, endocrine sensitivity may be a factor to be considered in the treatment preference.
The identification of prognostic factors in patients with renal cell carcinoma (RCC) represents an area of increasing interest. In this retrospective study, we evaluated the prognostic role of ...carbonic anhydrase-IX, ezrin, and neuropilin in metastatic RCC patients. The expression of several biomarkers were measured by immunohistochemistry (IHC) in 45 patients with advanced stage RCC treated with second-line tyrosine kinase inhibitors (TKIs) targeting vascular endothelial growth factor (VEGF) after failure of interferon-alpha between January 2007 and June 2012. Kaplan-Meier curves and log-rank tests were used for analysis of progression-free survival (PFS) and overall survival (OS), and a multivariate Cox proportional hazard model was employed to identify factors with an independent effect on the survival. Age, ezrin and neuropilin-2 overexpression were found to be statistically significant factors (
P
< 0.05) for PFS in the univariate analysis. Ezrin and neuropilin-2 overexpression, hemoglobin and albumin level were statistically significant factors (
P
< 0.05) for OS in the univariate analysis. Multivariate analysis revealed that low expression of ezrin and neuropilin-2 was an independent prognostic factor for PFS and OS. The median PFS was 4 months for patients overexpressing neuropilin-2 versus 11 months for those with lower expression of neuropilin-2 (
p
= 0.033). The median OS was longer in patients with low levels of neuropilin-2 expression (26 months) compared to patients overexpressing neuropilin-2 (13 months) (
p
= 0.023). Increased expression of ezrin was associated with poor prognosis in patients treated with TKIs targeting VEGF (PFS, 3 vs 7 months;
p
= 0.012). High ezrin expression was associated with shorter OS (
p
= 0.009). This is the first study in the literature showing that neuropilin-2 and ezrin are related with prognosis in patients with advanced RCC.
Summary
Background
In this retrospective study, we aimed to evaluate the clinicopathological characteristics of the patients presenting with liver metastases from unknown primary site besides ...survival rates, treatment outcomes, and prognostic factors.
Methods
In all, 68 patients followed-up at our center with adenocarcinoma of unknown primary (ACUP) metastatic to the liver between 2005 and 2013 were enrolled. All of the liver metastases were proven by liver biopsy and all yielded diagnosis of adenocarcinoma.
Results
Median age was 61 years (29–90) and most of the patients were male (male/female: 43/25). The liver was the only metastatic site in 2 (3 %) patients whilst 66 patients (97 %) had extrahepatic metastases. The most common extrahepatic metastatic sites were lymph nodes (89.7 %), lungs (32.4 %), bones (25 %), peritoneum (11.8 %), brain (4.4 %), and adrenal glands (2.9 %). Of all 68 patients, 39 (57.4 %) were treated with chemotherapy. Median overall survival (OS) was significantly higher in ACUP patients treated with chemotherapy 12.5 months (95 % CI 8.3–16.7) vs. 4 months (95 % CI 1.2–6.8), (
p
= 0.026), respectively. In multivariate analysis, ECOG (Eastern Cooperative Oncology Group) performance status (
p
= 0.009), chemotherapy (
p
= 0.024), serum albumin (
p
= 0.012), and serum CA 19-9 level (
p
= 0.026) at initial diagnosis were identified as independent prognostic factors influencing survival for the patients with liver metastases from ACUP.
Conclusion
Patients with liver metastases from ACUP have poor prognosis and chemotherapy improves survival. Decreased serum albumin level, increased CA 19-9 level and poor performance status are independent poor prognostic factors.
Recent advances in the understanding of underlying molecular signaling mechanisms of cancer susceptibility and progression have led to an increase in the use of targeted therapies for cancer ...treatment. Despite improvements in survival with new treatment options in oncology, resistance to therapy is a major obstacle to the long-term effectiveness of targeted agents in metastatic cancer treatment, culminating in insensitivity to treatment and tumor outgrowth. Adaptive resistance can play an important role in primary and upfront resistance to therapy as well as in secondary or acquired resistance. By focusing on colorectal and breast tumors, we discuss how therapeutic combinations based on specific drivers of tumor biology can be used to overcome resistance. We present how monitoring tumor dynamics over time may allow early adaptation of treatment. Breast cancer is the most common malignancy in women worldwide, and the majority of these cancers are sensitive to endocrine therapy (ET) blocking the production of or response to estrogen. However, primary and acquired resistance limits efficacy. Recent combinations of agents targeted to pathways that drive tumor growth resistance with ET have resulted in remarkable improvements in disease response and control, improving survival in some settings. In this review, we summarize adaptive resistance mechanisms, approaches to combination strategies, and dynamic tumor monitoring to improve efficacy and overcome resistance. We provide examples of combination therapy to enhance the efficacy of targeted therapies in breast and colorectal tumors.
Background: Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine carcinoma of the skin. In this study, we aimed to evaluate the clinicopathologic characteristics, treatment ...outcomes, and survival of MCC cases in Turkey.
Materials and Methods: The patients diagnosed with MCC between 1999 and 2018 at twenty different centers in Turkey were included in the study. Patient and tumor characteristics and adjuvant and metastatis treatment outcomes were analyzed retrospectively.
Results: The median age of totally 89 patients was 70 (26-93). The most common primary location was lower limbs (n = 29, 32.5%). Immunohistochemically, CK20 positivity was present in 59 patients (66.3%). Only two patients had secondary malignancy. The majority of the patients (n = 76, 85.4%) were diagnosed at the localized stage. Surgery was performed for all patients in the early stage, and adjuvant radiotherapy or/and chemotherapy was applied to 52.6% (n = 40) of nonmetastatic patients. The median follow-up was 29 months. Recurrence developed in 21 (27.6%) of the 76 patients who presented with local or regional disease. Two-year disease-free survival (DFS) was 68.1% and 5-year DFS was 62.0% for localized stage. The 5-year DFS was similar for patients receiving adjuvant treatment (chemotherapy, radiotherapy, or sequential chemoradiotherapy) and without adjuvant therapy (P > 0.05). Two-year overall survival in patients who presented with localized disease was 71.3% and 18.5% in metastatic patients (P < 0.001). In the metastatic stage, platinum/etoposide combination was the most preferred combination regimen. Median progression-free survival (PFS) in first-line chemotherapy was 7 months (95% confidence interval: 3.5-10.5 months; standart error: 1.78).
Conclusions: Although MCC is rare in Turkey, the incidence is increasing. Gender, CK20 status, tumor size, lymph node involvement, and adjuvant treatment were not associated with recurrence.
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