Efficacy and activity of treatments after progression from palbociclib plus endocrine therapy in patients with HR+/HER2- metastatic breast cancer: a prospective, monocentric study.

Background: Breast cancer is the most frequent tumour worldwide, and the HR+/HER2- subtype is the most common. For this tumour type, endocrine therapy (ET) is the mainstay of treatment. The association of ET and CDK4/6 inhibitors (CDK4/6i) represents the gold standard for first-line or second-line therapies. However, the optimal therapeutic strategy after CDK4/6i progression is still a matter of debate, with several randomized clinical trials still ongoing. Patients and methods: This is an observational, prospective, real-world study including women with HR+/HER2- metastatic breast cancer progressing to palbociclib plus ET. Patients received either ET or chemotherapy (CT). The primary objective was the evaluation of efficacy of the different therapeutic strategies after palbociclib in terms of median progression-free survival 2. Secondary objectives were the activity of therapeutic strategies measured with the clinical benefit rate, evaluation of the parameters used for the treatment choice, and progression-free survival 1 related to palbociclib plus ET treatment. Results: Overall, 48 patients (median age 53, range 33-78 years) were included. The median progression-free survival 2 was of 5 months in the overall cohort (95% CI 4-48 months) with a statistically significant difference between the two therapeutic strategies adopted (ET versus CT, 10 months versus 5 months, respectively). Regarding secondary objectives, the clinical benefit rate was 55.2% in the CT cohort and 50% in ET. Moreover, women treated with CT had a greater number of visceral metastases and a shorter median progression-free survival 1 than patients who received ET. Conclusions: ET and CT represent two possible therapeutic alternatives for patients progressing on CDK4/6i plus ET. The choice is based on clinical parameters, with a potential preference for ET.

Health-related quality of life and clinical complexity of a real-life cohort of patients with advanced HR+/HER2- breast cancer treated with CDK4/6 inhibitors and endocrine therapy.

Background: Advanced breast cancer (ABC) is characterized by multidimensional clinical complexity that is usually not considered in randomized clinical trials. In the present real-life study, we investigated the link between clinical complexity and quality of life of patients with HR+/HER2- ABC treated with CDK4/6 inhibitors. Methods: We evaluated multimorbidity burden assessed with the Cumulative Illness Rating Scale (CIRS), polypharmacy and patient-reported outcomes (PROs). PROs were assessed at baseline (T0), after 3 months of therapy (T1), and at disease progression (T2) using EORTC QLC-C30 and QLQ-BR23 questionnaires. Baseline PROs and changes between T0 and T1 were evaluated amongst patients with different multimorbidity burden (CIRS <5 and ≥5) and polypharmacy (<2 or ≥2 drugs). Results: From January 2018 to January 2022, we enrolled 54 patients (median age 66 years, IQR 59-74). The median CIRS score was 5 (IQR 2-7), whilst the median number of drugs taken by patients was 2 (IQR 0-4). No changes in QLQ-C30 final scoring between T0 and T1 were observed in the overall cohort (p=0.8944). At T2, QLQ-C30 global score deteriorated with respect to baseline (p=0.0089). At baseline, patients with CIRS ≥5 had worse constipation than patients without comorbidities (p<0.05) and a lower trend in the median QLQ-C30 global score. Patients on ≥2 drugs had lower QLQ-C30 final scores and worse insomnia and constipation (p<0.05). No change in QLQ-C30 final score from T0 to T1 was observed (p>0.05). Conclusion: Multimorbidity and polypharmacy increase the clinical complexity of patients with ABC and may affect baseline PROs. The safety profile of CDK4/6 inhibitors seems to be maintained in this population. Further studies are needed to assess clinical complexity in patients with ABC.This article is part of the Tackling clinical complexity in breast cancer Special Issue: https://www.drugsincontext.com/special_issues/tackling-clinical-complexity-in-breast-cancer/.

The prognostic role of variations in tumour markers (CEA, CA15.3) in patients with metastatic breast cancer treated with CDK4/6 inhibitors.

Tumour markers have no established role in the monitoring of the course of metastatic breast cancer during antineoplastic therapy, yet cancer antigen 15.3 (CA15.3) and carcinoembryonic antigen (CEA) are commonly used in clinical practice to aid in the early detection of progression of disease (PD). In our multicentre, prospective, real-life study, we enrolled 142 consecutive patients with advanced breast cancer receiving endocrine therapy in combination with a CDK4/6 inhibitor from January 2017 to October 2020; 75 patients had PD at the time of database closure. We measured serum marker concentrations at regular 4-month intervals together with radiological tumour response assessments and in cases of clinical suspicion of PD. Appropriate descriptive and inferential statistical methods were used to analyse serum marker level trends amongst prespecified subgroups and at specific time points (baseline, best radiologically documented tumour response and first detection of PD) in the subpopulation of patients with PD at the time of database closure. Notably, the median time from treatment initiation to best tumour response was 4.4 months. We evaluated the presence of an association between baseline CA15.3 and CEA levels and prespecified clinical characteristics but found no clinically meaningful correlation. We assessed marker level variations at the time of best radiologically documented disease response and PD: in the subgroup of patients who responded to treatment before progressing, we detected a statistically significant correlation with tumour marker variation between the time of best response and progression; this finding was not confirmed in the subgroup of patients that did not benefit from treatment. In conclusion, serum tumour marker flares can be useful in the early diagnosis of PD but should not be used as the sole factor prompting a change in treatment strategy without radiological confirmation.

Clinical and Biological Variables Influencing Outcome in Patients with Advanced Non-Small Cell Lung Cancer (NSCLC) Treated with Anti-PD-1/PD-L1 Antibodies: A Prospective Multicentre Study.

INTRODUCTION: Immune checkpoint inhibitors (ICIs) have become the standard of treatment for patients with non-small cell lung cancer (NSCLC). However, there are still many uncertainties regarding the selection of the patient who could benefit more from this treatment. This study aims to evaluate the prognostic and predictive role of clinical and biological variables in unselected patients with advanced NSCLC candidates to receive ICIs. METHODS: This is an observational and prospective study. The primary objective is the evaluation of the relationship between clinical and biological variables and the response to ICIs. Secondary objectives included: safety; assessment of the relationship between clinical and biological parameters/concomitant treatments and progression-free survival at 6 months and overall survival at 6 and 12 months. Nomograms to predict these outcomes have been generated. RESULTS: A total of 166 patients were included. An association with response was found in the presence of the high immunohistochemical PD-L1 expression, squamous cell histotype, and early line of treatment, whereas a higher probability of progression was seen in the presence of anemia, high LDH values and neutrophil/lymphocyte ratio (NLR), pleural involvement, and thrombosis before treatment. The nomogram showed that anemia, PD-L1 expression, NLR, and LDH represented the most informative predictor as regards the three parameters of interest. CONCLUSIONS: In the era of personalized medicine, the results are useful for stratifying the patients and tailoring the treatments, considering both the histological findings and the clinical features of the patients.

Perceived risk, illness perception and dispositional optimism related to COVID-19 among oncologic outpatients undergoing in-hospital treatments and healthy controls.

OBJECTIVE: This study aimed to explore risk estimations (perceived risk, dispositional optimism) related to COVID-19 perception and distress in oncologic outpatients undergoing active hospital treatments compared to the general population. DESIGN AND MAIN OUTCOME MEASURES: Data were collected during the Italian lockdown on 150 oncologic outpatients and a sample of 150 healthy subjects. They completed a battery of questionnaires including the Perceived Risk scale, the Brief Illness Perception Questionnaire, the Life Orientation Test- Revised and the Patient Health Questionnaire-4. Descriptive statistics, correlation analysis, and a moderated mediation model were performed to test the study hypotheses. RESULTS: The moderated mediation model attested significant conditional indirect associations of both clinical status and dispositional optimism with distress through the mediation of COVID-19 perceived risk. Healthy individuals and less optimistic people were more likely than others to report higher psychological distress only when they showed neutral or negative COVID-19-related illness perception. CONCLUSIONS: Cancer patients manifest a lower risk perception and a more positive illness representation related to COVID-19 compared to control subjects; the distress level is not associated with the clinical status, but it is moderated by illness perception. Adequate protective behaviors in cancer patients may avoid a dangerous underestimation of objective risks.

Patterns of treatment and outcome of palbociclib plus endocrine therapy in hormone receptor-positive/HER2 receptor-negative metastatic breast cancer: a real-world multicentre Italian study.

BACKGROUND: The CDK4/6 inhibitor palbociclib combined with endocrine therapy (ET) has proven to prolong progression-free survival (PFS) in women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (MBC). Few data are available regarding the efficacy of such a regimen outside the clinical trials. PATIENTS AND METHODS: This is a multicentre prospective real-world experience aimed at verifying the outcome of palbociclib plus ET in an unselected population of MBC patients. The primary aim was the clinical benefit rate (CBR); secondary aims were the median PFS, overall survival (OS) and safety. Patients received palbociclib plus letrozole 2.5 mg (cohort A) or fulvestrant 500 mg (cohort B). RESULTS: In total, 191 patients (92 in cohort A, 99 in cohort B) were enrolled and treated, and 182 were evaluable for the analysis. Median age was 62 years (range 47-79); 54% had visceral involvement; 28% of patients had previously performed one treatment line (including chemotherapy and ET), 22.6% two lines and 15.9% three. An overall response rate of 34.6% was observed with 11 (6.0%) complete responses and 52 (28.6%) partial responses. Stable disease was achieved by 78 patients (42.9%) with an overall CBR of 59.8%. At a median follow-up of 24 months (range 6-32), median PFS was 13 months without significant differences between the cohorts. When analysed according to treatment line, PFS values were significantly prolonged when palbociclib-based therapy was administered as first-line treatment (14.0 months), to decrease progressively in second and subsequent lines (11.7 and 6.7 months, respectively). Median OS was 25 months, ranging from 28.0 months in 1st line to 18.0 and 13.0 months in 2nd and subsequent lines, respectively. CONCLUSIONS: Our data indicate that palbociclib plus ET is active and safe in HR+/HER2- MBC, also suggesting a better performance of the combinations in earlier treatment lines.

Impact of COVID-19 Outbreak on Cancer Patient Care and Treatment: Data from an Outpatient Oncology Clinic in Lombardy (Italy).

Lombardy was the first area in Italy to have an outbreak of coronavirus disease 19 (COVID-19) at the beginning of 2020. In this context, cancer has been reported as a major risk factor for adverse outcomes and death, so oncology societies have quickly released guidelines on cancer care during the pandemic. The aim of this study was to investigate the management of cancer patients and oncological treatments during the COVID-19 pandemic and to describe the containment measures performed in our outpatient clinic at Pavia (Lombardy). A comparison with the same period of the four previous years (2019, 2018, 2017, and 2016) was also performed. Using our electronic databases, we evaluated the number and characteristics of patients accessing the hospital for anticancer drug infusion from 24 February, 2020 to 30 April, 2020 and the number of radiological exams performed. Although a significant reduction in access for therapy was seen when compared with 2019 (2590 versus 2974, access rate ratio (ARR) = 0.85, p < 0.001), no significant differences in access numbers and ARR was evident between 2020 and 2018, 2017, or 2016 (2590 versus 2626 (ARR = 0.07), 2660 (ARR = 0.99), and 2694 (ARR = 0.96), respectively, p > 0.05). In 2020, 63 patients delayed treatment: 38% for "pandemic fear", 18% for travel restrictions, 13% for quarantine, 18% for flu syndrome other than COVID-19, and 13% for worsening of clinical conditions and death. Only 7/469 patients developed COVID-19. A significant reduction in radiological exams was found in 2020 versus all the other years considered (211 versus 360, 355, 385, 390 for the years 2020, 2019, 2018, 2017, and 2016, respectively, p < 0.001). The low incidence of COVID-19 among our cancer patients, along with the hospital policy to control infection, enabled safe cancer treatment and a continuum of care in most patients, while a small fraction of patients experienced a therapeutic delay due to patient-related reasons.

Role of androgen receptor expression in early stage ER+/PgR-/HER2- breast cancer.

BACKGROUND: Progesterone receptor (PgR) negative breast cancer (BC) is an aggressive subtype with poor prognosis and reduced response to endocrine treatments. Several studies have suggested that androgen receptor (AR) expression is associated with a favorable tumor biology, longer recurrence free survival (RFS), and overall survival. In the literature no data exist regarding the role of AR expression in early stage estrogen receptor (ER)+/PgR- BCs. The aim of this study was to evaluate the prognostic role of AR expression in this setting. PATIENTS AND METHODS: This is a monocentric retrospective study in which 208 patients who underwent surgical intervention for ER+/PgR-/Human Epidermal growth factor Receptor 2 (HER2)- BC were included. The primary objective was to analyze the relationship between AR expression and RFS. RESULTS: At a median follow-up of 77 months, 75 patients (36%) had a disease relapse (all sites included). AR expression was significantly higher in patients who did not relapse compared with those who relapsed with an impact on RFS (hazard ratio [HR] = 0.99, p = 0.025). Patients with AR expression ⩾80% had a lower risk of relapse compared with those with AR <80% (HR = 0.53, p = 0.008). In addition, breast tumors with higher AR expression had good biological features (low ki67 and nuclear grade) compared with BCs with lower AR expression, at least partly explaining the different outcome. CONCLUSIONS: The results of this study support the potential prognostic role of AR in patients with ER+/PgR- BCs and may contribute to the identification of subgroups of high-risk patients.

Patterns of treatment and outcome with 500-mg fulvestrant in postmenopausal women with hormone receptor-positive/HER2-negative metastatic breast cancer: a real-life multicenter Italian experience.

BACKGROUND: Fulvestrant 500 mg (F500) is the most active endocrine single agent in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (MBC). Few data are available regarding the effectiveness of the drug in a real-world setting. PATIENTS AND METHODS: This prospective, multicenter cohort study aimed to describe the patterns of treatment and performance of F500 in a large population of unselected women with MBC, focusing on potential prognostic or predictive factors for disease outcome and response. The primary endpoints were progression-free survival (PFS) and clinical benefit rate. RESULTS: From January 2011 to December 2015, 490 consecutive patients treated with F500 were enrolled. Overall, three different cohorts were identified and analyzed: the first received F500 after progression from previous chemotherapy (CT) or endocrine therapy; the second received the drug for de novo metastatic disease; and the third was treated as maintenance following disease stabilization or a response from a previous CT line. Median overall survival (OS) in the whole population was 26.8 months, ranging from 32.4 in first line to 22.0 and 13.7 months in second line and subsequent lines, respectively. Both the presence of liver metastasis and the treatment line were significantly associated with a worse PFS, while only the presence of liver metastasis maintained its predictive role for OS in multivariate analysis. CONCLUSIONS: The effectiveness of F500 was detected in patients treated both upon disease progression and as maintenance. The relevant endocrine sensitivity of 80% of patients included in the study could probably explain the good results observed in terms of outcome.

Vinflunine in Advanced Transitional Cell Cancer of the Urothelial Tract: A Potential Option for Maintenance Therapy? A Case Series.

INTRODUCTION: Vinflunine is a microtubule inhibitor approved in Europe as second-line treatment of advanced transitional cell cancer of the urothelium (TCCU). The inability to continue with a first-line platinum-based regimen beyond 6 cycles suggested investigating the use of vinflunine as switch maintenance therapy in patients with response or stable disease after first-line therapy. METHODS: Patients with advanced TCCU and documented disease control after 3-6 cycles of first-line platinum-based chemotherapy received vinflunine maintenance therapy within 6 weeks of the last cycle. Our analysis aimed to examine the performance of vinflunine in terms of activity and safety in such a patient population. RESULTS: 28 consecutive patients were studied. After a median follow-up of 25 months, vinflunine was associated with a median progression-free survival of 9 months (range 4 to > 16 months) and a disease control rate of 64%; median overall survival was not reached. Treatment was well tolerated, with no unexpected safety events. The most common adverse events of grade ≥ 3 were neutropenia (21%) and constipation (14%); no toxicity-related death occurred. CONCLUSIONS: Our results suggest that vinflunine may be a suitable maintenance treatment option for TCCU patients who received a maximum of 6 cycles of platinum-based chemotherapy commonly used as first-line treatment.

Nivolumab Induced Thyroid Dysfunction: Unusual Clinical Presentation and Challenging Diagnosis.

In recent years, immune checkpoint inhibitors (ICIs) had a great impact in cancer therapy. ICIs display a peculiar toxicity profile, which is characterized by autoimmune-like manifestations against multiple organs, including endocrine glands. We hereby report the case history of two patients who experienced nivolumab-induced endocrine immuno-related adverse events (irAEs). Thyroid dysfunction in both patients presented with a low serum level of TSH. However, endocrine evaluation showed a completely different etiology and clinical evolution. The two patients' histories indicate that nivolumab can cause a large spectrum of thyroid and endocrine dysfunctions resulting in cumbersome diagnostic problems. In these peculiar patients the evaluation of endocrine experts is warranted.

Renal cell carcinoma and malignant peritoneal mesothelioma after occupational asbestos exposure: case report.

UNLABELLED: Asbestos is the main causal factor for malignant mesothelioma (MM), a relatively rare and aggressive malignancy. Some epidemiological evidence suggests a role of this agent also in the etiology of renal cell carcinoma (RCC), the most common form of kidney cancer. CASE REPORT: After 7 years of asbestos exposure, a 76-year-old asbestos-cement worker came to our notice with left flank pain. Diagnostic imaging disclosed a neoplasm in the upper two thirds of the left kidney, without evidence of metastases. After surgery (nephrectomy with para-aortic lymphadenectomy), histopathology revealed clear cell RCC. One year later, the patient was hospitalized for abdominal pain. Laparoscopy showed diffuse neoplastic infiltration of the peritoneum and liver. Histological and immunohistochemical examination of the bioptic samples led to the diagnosis of biphasic MM. The subject died 2 months later. Autopsy disclosed ascites and diffuse infiltration of the abdominal wall and viscera, without evidence of RCC relapse. CONCLUSIONS: This is the second reported case of association between RCC and peritoneal MM in the scientific literature. Asbestos might be involved in the causation of both malignancies.

Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer patients: prospective evaluation of activity, safety, and quality of life.

BACKGROUND: A prospective, multicenter trial was undertaken to assess the activity, safety, and quality of life of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) as second-line chemotherapy in HER2-negative, taxane-pretreated metastatic breast cancer (MBC). PATIENTS AND METHODS: Fifty-two women with HER2-negative MBC who were candidates for second-line chemotherapy for the metastatic disease were enrolled and treated at three centers in Northern Italy. All patients had previously received taxane-based chemotherapy in the adjuvant or first-line metastatic setting. Single-agent nab-paclitaxel was given at the dose of 260 mg/m(2) as a 30-minute intravenous infusion on day 1 each treatment cycle, which lasted 3 weeks, in the outpatient setting. No steroid or antihistamine premedication was provided. Treatment was stopped for documented disease progression, unacceptable toxicity, or patient refusal. RESULTS: All of the enrolled patients were evaluable for the study endpoints. The objective response rate was 48% (95% CI, 31.5%-61.3%) and included complete responses from 13.5%. Disease stabilization was obtained in 19 patients and lasted >6 months in 15 of them; the overall clinical benefit rate was 77%. The median time to response was 70 days (range 52-86 days). The median progression-free survival time was 8.9 months (95% CI, 8.0-11.6 months, range 5-21+ months). The median overall survival point has not yet been reached. Toxicities were expected and manageable with good patient compliance and preserved quality of life in patients given long-term treatment. CONCLUSION: Our results showed that single-agent nab-paclitaxel 260 mg/m(2) every 3 weeks is an effective and well tolerated regimen as second-line chemotherapy in HER2-negative, taxane-pretreated MBC patients, and that it produced interesting values of objective response rate and progression-free survival without the concern of significant toxicity. Specifically, the present study shows that such a regimen is a valid therapeutic option for that 'difficult to treat' patient population represented by women who at the time of disease relapse have already received the most active agents in the adjuvant and/or metastatic setting (ie, conventional taxanes).

Which patients with metastatic breast cancer benefit from subsequent lines of treatment? An update for clinicians.

The outcome of patients with metastatic breast cancer (MBC) has clearly improved over the past decades and the proportion of women living with their disease for several years is increasing. However, the usefulness of multiple lines of treatment is still debated and under evaluation. The available data from both randomized trials and large retrospective series are reviewed and discussed in order to analyze management practices, with emphasis on potential prognostic and predictive factors for clinical outcome. At present, evidence-based medicine provides some support for the use of second-line and to a lesser degree and in selected cases, third-line chemotherapy in human epidermal growth factor receptor 2 (HER2) negative MBC. Beyond third-line treatment, messages from recently reported retrospective studies also suggest a clear potential gain for women receiving further therapies after disease progression, since each line can contribute to a longer survival. In HER2-positive disease, the data from observational and retrospective studies support a clinical benefit from the use of trastuzumab beyond disease progression and emerging evidences from randomized controlled trials are leading to the introduction of newer HER2-targeted therapies in multiple lines. The question 'How many lines of treatment should we give patients?' clearly needs further research through prospective, high-quality clinical trials, aiming for a better definition of factors with prognostic and predictive role. In the meantime, the 'optimal' treatment strategy should probably be to use as many therapeutic options as possible, either in sequence or combination, to keep the best efficacy/toxicity balance, considering MBC as a chronic disease.

Intravenous or oral vinorelbine plus capecitabine as first-line treatment in HER2- metastatic breast cancer: joint analysis of 2 consecutive prospective phase II trials.

BACKGROUND: The purpose of this study was to assess the activity and safety of the combination of vinorelbine (VNR) and capecitabine (CAP) as first-line treatment in HER2-negative (HER(-)) metastatic breast cancer (MBC). PATIENTS AND METHODS: Patients (42) enrolled in trial A received intravenous (i.v.) VNR 25 mg/m2 on days 1 and 8 of a 21-day cycle combined with CAP 1000 mg/m2 twice daily for 14 consecutive days followed by 1 week of rest. Trial B (46 patients) followed trial A when the oral formulation of VNR became available at our institution. Patients received oral VNR (60 mg/m(2) on days 1-8) combined with the same CAP schedule as in trial A. RESULTS: The response rate (RR) in trial A was 73.2% (95% confidence interval [CI], 56.4-82.8), including 12.2% complete responses (CRs). Clinical benefit was achieved in 78% of patients (95% CI, 63.2-87.9). In trial B, overall RR was 76% (95% CI, 62.0-86.0), with 13% CRs and clinical benefit of 80.4% (95% CI, 66.8-89.3). In trial A, median progression-free survival (PFS) was 8.2 months (range, 6-14+ months) and median overall survival (OS) was 32.4 months (range, 17-36+ months). In trial B, median PFS and OS were 8.8 months (range, 8-21+ months) and 34.3 months (14-39+ months), respectively. Treatment-related toxicity was manageable. Quality of life assessment showed a statistically significant difference regarding body image (p = .001), sexual functioning (p = .02), and future perspectives (p = .03) in women receiving chemotherapy fully by the oral route. CONCLUSION: This joint analysis shows that both tested schedules can produce high objective RRs with encouraging PFS, manageable toxicity profile, and suggested benefit on some aspects of quality of life for the fully oral combination.

Oxaliplatin-eluting microspheres for the treatment of intrahepatic cholangiocarcinoma: a case report.

Intrahepatic cholangiocarcinoma account for 13% of annual cancer-related deaths worldwide and for 3% in the USA. Patient with unresectable disease can benefit from palliative therapies such as systemic chemotherapy. However, the only curative treatment for intrahepatic cholangiocarcinoma is complete surgical resection with histologically negative resection margins.

Simultaneous determination of cyclophosphamide, ifosfamide, doxorubicin, epirubicin and daunorubicin in human urine using high-performance liquid chromatography/electrospray ionization tandem mass spectrometry: bioanalytical method validation.

A reversed-phase high-performance liquid chromatography (rp-HPLC) system interfaced with an electrospray ionization (ESI) source coupled to tandem mass spectrometry (MS/MS) was developed and validated for the determination of cyclophosphamide (CP), ifosfamide (IF), daunorubicin (DNR), doxorubicin (DXR), and epirubicin (EPI) in human urine. The analysis of samples containing multiple analytes with a dissimilar range of polarities was carried out using a conventional reversed-phase chromatographic BDS Hypersil C8 column. The analytical run was 15 min. The triple quadrupole mass spectrometer was operated in positive ion mode and multiple reaction monitoring (MRM) was used for drug quantification. The method was validated over a concentration range of 0.2 to 4.0 microg.L(-1) for CP, IF, DXR, EPI and 0.15-2.0 microg.L(-1) for DNR in human urine. The lower limit of quantification (LLOQ) was 0.2 microg.L(-1) for CP, IF, EPI and was set at 0.3 and 0.15 microg.L(-1) for DXR and DNR, respectively. The relative standard deviations (RSD%) were <11.2% for inter- and intra-day precisions. The overall accuracy was also within 114.7% for all analytes at the concentrations of the quality control samples. The potential of ionization suppression resulting from the endogenous biological material on the rp-HPLC/MS/MS method was evaluated and measured. The feasibility of the proposed HPLC/ESI-MS/MS procedure was demonstrated by analyzing urine samples from pharmacy technicians and nurses working in hospitals or personnel employed in drug-manufacturing plants.

Transhepatic arterial chemoembolization with oxaliplatin-eluting microspheres (OEM-TACE) for unresectable hepatic tumors.

BACKGROUND: While conventional transhepatic arterial chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma (HCC), its use in other hepatic tumors is not supported by randomized studies. Preliminary results have shown that new drug-eluting microspheres (DEM) seem to optimize TACE procedures. The aim of this study was to evaluate the capability of HepaSphere to load oxaliplatin and their pharmacokinetic outcome. The feasibility and safety of treatment with oxaliplatin-eluting microspheres (OEM-TACE) was also evaluated in patients with unresectable liver metastasis of colorectal cancer and unresectable intrahepatic cholangiocarcinoma. PATIENTS AND METHODS: An inductively coupled plasma mass spectrometer (ICP-MS) was used to quantify the oxaliplatin bound to microspheres and the oxaliplatin in liver biopsies. Fifteen patients (8 with colorectal carcinoma liver metastases, 7 with intrahepatic cholangiocarcinoma) were treated with 27 sessions of OEM-TACE. RESULTS: The data suggested that the microspheres can bind oxaliplatin entirely. The pharmacokinetic parameters were significantly different between the OEM-TACE patients and a control group of patients treated with oxaliplatin chemotherapy. The mean oxaliplatin concentration within the tumor was twenty-times higher than the extratumoral liver concentration in the OEM-TACE patients. According to response evaluating criteria in solid tumors (RECIST), stable disease was observed in 8 out of the 15 patients (53.3%), a partial response in 2 (13.3%) and intrahepatic or extrahepatic tumor progression in 5 out of the 15 patients (33.3%). No major adverse event (AE G3/4) occurred. CONCLUSION: TACE with oxaliplatin-loaded microspheres is a safe and feasible treatment without major adverse events and with a favorable pharmacokinetic profile.

Complications of percutaneous radiofrequency thermal ablation of primary and secondary lesions of the liver.

Hepatocellular carcinoma is one of the most common malignancies in the world, with the liver being the second most frequently involved organ in metastatic disease. Although the gold standard treatment for malignant liver disease is surgical resection, only few patients can undergo such an intervention. This explains the current great interest in various loco-regional therapies, of which radiofrequency thermal ablation (RFA) is the most common. To date, only a few studies have evaluated the complications associated with this treatment. The aim of this study was to determine the rate of complications, divided into major and minor, in patients treated with RFA. A total of 373 hepatic lesions in 250 patients were treated with 292 sessions of percutaneous ultrasound-guided RFA. According to our data, ten patients (4%) had major, complications, twelve patients (4.8%) had minor complications, no deaths occurred. Around 30% of patients had a body temperature increase of up to 38 'C. All complications, except one, were treated with nonsurgical therapies. One patient with massive hemoperitoneum required surgery. In conclusion, percutaneous RFA is a loco-regional therapy associated with a low incidence of side-effects and a negligible risk of death.