Classification of anticancer drugs: an update with FDA- and EMA-approved drugs.

Anticancer systemic therapy comprises a complex and growing group of drugs. Some of the new agents with novel mechanisms of action that have appeared are difficult to fit in the groups of classical chemotherapy, hormones, tyrosine-kinase inhibitors, and monoclonal antibodies. We propose a classification based on two levels of information: the site of action and the mechanism of action. Regarding the former, drugs can exert their action in the tumor cell, the tumor vasculature, the immune system, or the endocrine system. The mechanism of action refers to the molecular target.

Prospective Study Comparing Clinicians' and Cancer Patients' Estimates of Risk of Relapse and Toxicity with Adjuvant Chemotherapy.

The aim of this study was to compare physicians' and patients' estimates of risk of relapse and toxicity. A prospective, cross-sectional, multicenter study including 735 patients with cancer and 29 oncologists. Physicians' appraisals of risk of relapse with and without chemotherapy (27.5% and 43.1%) and risk of severe toxicity (12.2%) were more realistic than those of patients (34.6%, 78.5%, and 57.4%, respectively). The greater the risk of recurrence and risk of toxicity estimated, the less physicians expressed satisfaction with SDM. Estimations of risk of relapse and toxicity are important in diagnostic and therapeutic decision-making and can help patients face their situation.

Concomitant Medications and Risk of Chemotherapy-Induced Peripheral Neuropathy.

BACKGROUND: Peripheral neuropathy is the dose-limiting toxicity of many oncology drugs, including paclitaxel. There is large interindividual variability in the neuropathy, and several risk factors have been proposed; however, many have not been replicated. Here we present a comprehensive study aimed at identifying treatment and physiopathology-related paclitaxel-induced neuropathy risk factors in a large cohort of well-characterized patients. PATIENTS AND METHODS: Analyses included 503 patients with breast or ovarian cancer who received paclitaxel treatment. Paclitaxel dose modifications caused by the neuropathy were extracted from medical records and patients self-reported neuropathy symptoms were collected. Multivariate logistic regression analyses were performed to identify concomitant medications and comorbidities associated with paclitaxel-induced neuropathy. RESULTS: Older patients had higher neuropathy: for each increase of 1 year of age, the risk of dose modifications and grade 3 neuropathy increased 4% and 5%, respectively. Cardiovascular drugs increased the risk of paclitaxel dose reductions (odds ratio [OR], 2.51; p = .006), with a stronger association for beta-adrenergic antagonists. The total number of concomitant medications also showed an association with dose modifications (OR, 1.25; p = .012 for each concomitant drug increase). A dose modification predictive model that included the new identified factors gave an area under the curve of 0.74 (p = 1.07 × 10-10). Preexisting nerve compression syndromes seemed to increase neuropathy risk. CONCLUSION: Baseline characteristics of the patients, including age and concomitant medications, could be used to identify individuals at high risk of neuropathy, personalizing chemotherapy treatment and reducing the risk of severe neuropathy. IMPLICATIONS FOR PRACTICE: Peripheral neuropathy is a common adverse effect of many cancer drugs, including chemotherapeutics, targeted therapies, and immune checkpoint inhibitors. About 40% of survivors of cancer have functional deficits caused by this toxicity, some of them irreversible. Currently, there are no effective treatments to prevent or treat this neuropathy. This study, performed in a large cohort of well-characterized patients homogenously treated with paclitaxel, identified concomitant medications, comorbidities, and demographic factors associated with peripheral neuropathy. These factors could serve to identify patients at high risk of severe neuropathy for whom alternative non-neurotoxic alternatives may be considered.

Biopsychosocial and clinical characteristics in patients with resected breast and colon cancer at the beginning and end of adjuvant treatment.

BACKGROUND: The aim of this study was to analyze biopsychosocial factors affecting how patients cope with cancer and adjuvant treatment and to appraise psychological distress, coping, perceived social support, quality of life and SDM before and after adjuvant treatment in breast cancer patients compared to colon cancer patients. METHODS: NEOcoping is a national, multicenter, cross-sectional, prospective study. The sample comprised 266 patients with colon cancer and 231 with breast cancer. The instruments used were the Brief Symptom Inventory (BSI), Mini-Mental Adjustment to Cancer (Mini-MAC), Multidimensional Scale of Perceived Social Support (MSPSS), Shared Decision-Making Questionnaire-Patient (SDM-Q-9) and Physician's (SDM-Q-Doc), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ). RESULTS: Breast cancer patients reacted worse to the diagnosis of cancer with more symptoms of anxiety, depression, and somatization, and were less satisfied with their involvement than those with colon cancer (p = 0.003). Participants with colon cancer were older and had more physical symptoms and functional limitations at the beginning of adjuvant treatment, while there were scarcely any differences between the two groups at the end of adjuvancy, at which time both groups suffered greater psychological and physical effects and scored lower on coping strategies, except for anxious preoccupation. CONCLUSIONS: Breast cancer patients need more information and involvement of the oncologist in shared decision-making, as well as and more medical and psychological support when beginning adjuvant treatment. Both breast and colon cancer patients may require additional psychological care at the end of adjuvancy.

Psychometric properties and factorial analysis of invariance of the Satisfaction with Life Scale (SWLS) in cancer patients.

PURPOSE: The purpose of this study was to assess the psychometric properties of the Satisfaction with Life Scale (SWLS), evaluate the measurement invariance with respect to sex, age, and tumor location, as well as analyze associations between life satisfaction and socio-demographic and clinical variables among individuals with resected, non-advanced cancer. METHODS: A confirmatory factor analysis was conducted to explore the dimensionality of the scale and test invariance across gender, age, and tumor localization in a prospective, multicenter cohort of 713 patients who completed the following scales: SWLS, Health-related Quality of Life Questionnaire (EORTC QLQ-C30), Brief Symptom Inventory (BSI-18). RESULTS: Confirmatory factor analysis results indicated that the SWLS is an essentially unidimensional instrument, providing accurate scores: both McDonald's omega and Cronbach's alpha estimates were 0.91. Strong measurement invariance was found to hold across gender, age, and tumor localization. Low satisfaction with life was associated with psychological symptoms (anxiety, depression, and somatization), and decreased quality of life (malfunction, symptoms, poor global QoL). CONCLUSION: The SWLS is a reliable, valid satisfaction with life measurement among people with cancer and should be recommended as an indicator of psychological adjustment in oncological patients.

Differences in coping strategies among young adults and the elderly with cancer.

BACKGROUND: Coping with cancer and the oncologist-patient relationship can vary depending on the patient's age. Our aim is to examine and compare young and elderly adults with non-metastatic, resected cancer. METHODS: Two groups of patients were selected, young (< 40 years) and elderly (> 70) with a diagnosis of non-metastatic, resected cancer requiring adjuvant chemotherapy from a pre-exiting, national database (NEOCOPING Study). Epidemiological variables were collected and subjects' emotional responses, perceptions of the physician-patient relationship, support network, fears, and regret about the decision to receive chemotherapy were assessed with questionnaires validated in previous studies: Mini-Mental Adjustment to Cancer, Brief Summary Inventory (18 items), European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire-C30, Shared Decision-Making Questionnaire-Physician's version, Shared Decision-Making Questionnaire-Patient's version, and Informed Risk (physician and patient versions). RESULTS: Data from 46 young and 46 elderly participants were collected. The most common neoplasms in both groups were breast (50%) and colorectal (22%). The younger adults had a higher level of education and were actively employed (72% vs. 7%). The leading coping strategy in the younger cohort was hope, and resignation among the elderly. Young adults sought more social support and the impact of diagnosis was more negative for them than for older individuals. No significant differences were detected in quality of life; both age groups demanded more time at their first visit with the doctor, while the older group exhibited greater satisfaction with shared decision-making. At the end of adjuvant chemotherapy, neither age group regretted their decision to receive said treatment. CONCLUSION: Higher levels of education, greater demands of the labour market, and the advent of the age of information have entailed drastic changes in the physician-patient relationship paradigm. This is especially true in the younger cancer patient population, who require more information and active participation in decision-making, can display more anxiety about their diagnosis, but also greater capacity to fight.

DUSP1 and SOX2 expression determine squamous cell carcinoma of the salivary gland progression.

Salivary gland squamous cell carcinomas (SG-SCCs) constitute a rare type of head and neck cancer which is linked to poor prognosis. Due to their low frequency, the molecular mechanisms responsible for their aggressiveness are poorly understood. In this work we studied the role of the phosphatase DUSP1, a negative regulator of MAPK activity, in controlling SG-SCC progression. We generated DUSP1 KO clones in A253 human cells. These clones showed a reduced ability to grow in 2D, self-renew in ECM matrices and to form tumors in immunodeficient mice. This was caused by an overactivation of the stress and apoptosis kinase JNK1/2 in DUSP1-/+ clones. Interestingly, RNAseq analysis revealed that the expression of SOX2, a well-known self-renewal gene was decreased at the mRNA and protein levels in DUSP1-/+ cells. Unexpectedly, CRISPR-KO of SOX2 did not recapitulate DUSP1-/+ phenotype, and SOX2-null cells had an enhanced ability to self-renew and to form tumors in mice. Gene expression analysis demonstrated that SOX2-null cells have a decreased squamous differentiation profile -losing TP63 expression- and an increased migratory phenotype, with an enhanced epithelial to mesenchymal transition signature. In summary, our data indicates that DUSP1 and SOX2 have opposite functions in SG-SCC, being DUSP1 necessary for tumor growth and SOX2 dispensable showing a tumor suppressor function. Our data suggest that the combined expression of SOX2 and DUSP1 could be a useful biomarker to predict progression in patients with SG-SCCs.

Long-term complete remission of metastatic adrenocortical carcinoma.

OBJECTIVES: To report a rare case of a metastatic adrenocortical carcinoma (ACC) that achieve a complete and a long-term remission. CASE PRESENTATION: AAC is a rare and aggressive tumor, with a high risk of recurrence and that present metastases in 21% of cases at diagnosis. Treatment of advanced ACC is challenging, mitotane is the only available adrenolytic treatment, with modest and unpredictable responses. Response rates to systemic chemotherapy are not encouraging. We describe the case of a 39-year-old woman with a metastatic ACC, that achieve a complete and long-term remission after chemotherapy, mitotane treatment and surgery of primary tumor and liver metastases. CONCLUSIONS: A complete remission of a metastatic adrenocortical carcinoma is possible in some rare cases after a multimodal treatment.

Targeting the endothelin axis in prostate carcinoma.

Prostate cancer is the most common malignancy in men in Western countries. Until the last decade, the main available therapeutic options were based on hormonal therapy. For castration-refractory prostate carcinoma, from 2004, the combination of chemotherapy with docetaxel and prednisone has shown to improve survival in this subset of patients. Many agents have been tested either alone or in combination with this standard therapy, trying to find synergistic effects between drugs, and to target specific pathways that influence tumor growth, invasiveness, angiogenesis, and the development of distant metastasis. Endothelin antagonists have been recently studied, as they can get involved in many of these oncogenic pathways, and results are encouraging; nevertheless, the right setting to use them, whether to use them in monotherapy or in combination with other agents, and if they really improve the survival of our patients, are questions that remain to be addressed. In this review, we summarize the role of endothelins in tumoral biology and specifically in prostate carcinoma natural history, and the results obtained in the clinical trials involving this new therapeutic group.

Use of multikinase inhibitors/lenvatinib in singular thyroid cancer scenarios.

Thyroid cancer is the most frequent endocrine tumor. In locally advanced or metastatic disease there are only two types of treatment available: radioactive iodine (RAI) while the disease is RAI-sensitive and multikinase inhibitors, lenvatinib and sorafenib, when the disease becomes RAI-refractory. The objective of this publication is to review the current knowledge on the use of targeted therapy and the specific practical considerations concerning lenvatinib in the treatment of patients with differentiated thyroid cancer under special circumstances.

Mechanisms of Cisplatin Resistance in HPV Negative Head and Neck Squamous Cell Carcinomas.

Head and neck squamous cell carcinomas (HNSCCs) are the eighth most common cancers worldwide. While promising new therapies are emerging, cisplatin-based chemotherapy remains the gold standard for advanced HNSCCs, although most of the patients relapse due to the development of resistance. This review aims to condense the different mechanisms involved in the development of cisplatin resistance in HNSCCs and highlight future perspectives intended to overcome its related complications. Classical resistance mechanisms include drug import and export, DNA repair and oxidative stress control. Emerging research identified the prevalence of these mechanisms in populations of cancer stem cells (CSC), which are the cells mainly contributing to cisplatin resistance. The use of old and new CSC markers has enabled the identification of the characteristics within HNSCC CSCs predisposing them to treatment resistance, such as cell quiescence, increased self-renewal capacity, low reactive oxygen species levels or the acquisition of epithelial to mesenchymal transcriptional programs. In the present review, we will discuss how cell intrinsic and extrinsic cues alter the phenotype of CSCs and how they influence resistance to cisplatin treatment. In addition, we will assess how the stromal composition and the tumor microenvironment affect drug resistance and the acquisition of CSCs' characteristics through a complex interplay between extracellular matrix content as well as immune and non-immune cell characteristics. Finally, we will describe how alterations in epigenetic modifiers or other signaling pathways can alter tumor behavior and cell plasticity to induce chemotherapy resistance. The data generated in recent years open up a wide range of promising strategies to optimize cisplatin therapy, with the potential to personalize HNSCC patient treatment strategies.

Prognosis Stratification Tools in Early-Stage Endometrial Cancer: Could We Improve Their Accuracy?

There are three prognostic stratification tools used for endometrial cancer: ESMO-ESGO-ESTRO 2016, ProMisE, and ESGO-ESTRO-ESP 2020. However, these methods are not sufficiently accurate to address prognosis. The aim of this study was to investigate whether the integration of molecular classification and other biomarkers could be used to improve the prognosis stratification in early-stage endometrial cancer. Relapse-free and overall survival of each classifier were analyzed, and the c-index was employed to assess accuracy. Other biomarkers were explored to improve the precision of risk classifiers. We analyzed 293 patients. A comparison between the three classifiers showed an improved accuracy in ESGO-ESTRO-ESP 2020 when RFS was evaluated (c-index = 0.78), although we did not find broad differences between intermediate prognostic groups. Prognosis of these patients was better stratified with the incorporation of CTNNB1 status to the 2020 classifier (c-index 0.81), with statistically significant and clinically relevant differences in 5-year RFS: 93.9% for low risk, 79.1% for intermediate merged group/CTNNB1 wild type, and 42.7% for high risk (including patients with CTNNB1 mutation). The incorporation of molecular classification in risk stratification resulted in better discriminatory capability, which could be improved even further with the addition of CTNNB1 mutational evaluation.

Initial clinical and treatment patterns of advanced differentiated thyroid cancer: ERUDIT study.

Background: Up to 30% of differentiated thyroid cancer (DTC) will develop advanced-stage disease (aDTC) with reduced overall survival (OS). Objective: The aim of this study is to characterize initial diagnosis of aDTC, its therapeutic management, and prognosis in Spain and Portugal. Methods: A multicentre, longitudinal, retrospective study of adult patients diagnosed with aDTC in the Iberian Peninsula was conducted between January 2007 and December 2012. Analyses of baseline characteristics and results of initial treatments, relapse- or progression-free survival ((RP)FS) from first DTC diagnosis, OS, and prognostic factors impacting the evolution of advanced disease were evaluated. Results: Two hundred and thirteen patients (median age: 63 years; 57% female) were eligible from 23 hospitals. Advanced disease presented at first diagnosis (de novo aDTC) included 54% of patients, while 46% had relapsed from early disease (recurrent/progressive eDTC). At initial stage, most patients received surgery (98%) and/or radioiodine (RAI) (89%), with no differences seen between median OS (95% CI) (10.4 (7.3-15.3) years) and median disease-specific-survival (95% CI) (11.1 (8.7-16.2) years; log-rank test P = 0.4737). Age at diagnosis being <55 years was associated with a lower risk of death (Wald chi-square (Wc-s) P < 0.0001), while a poor response to RAI to a higher risk of death ((Wc-s) P < 0.05). In the eDTC cohort, median (RP)FS (95% CI) was of 1.7 (1.0-2.0) years after RAI, with R0/R1 surgeries being the only common significant favourable factor for longer (RP)FS and time to aDTC ((Wc-s) P < 0.05). Conclusion: Identification of early treatment-dependent prognostic factors for an unfavourable course of advanced disease is possible. An intensified therapeutic attitude may reverse this trend and should be considered in poor-performing patients. Prospective studies are required to confirm these findings.

Cancer survivors referred to a long-term survivorship outpatient service within academic medical oncology: descriptive study.

PURPOSE: Long-term cancer survivors (LTCS) are a vulnerable and continued growing population. To date, only few studies have been conducted in the Spanish population; none of them with a comprehensive analysis of the most common problems identified for cancer survivors in order to improve their care and quality of life. METHODS: We conducted an observational descriptive study in 347 patients recruited between January 2015 and December 2016 from our newly created medical office for the specific care and follow-up of LTCS. Variables that describe the medical history were completed by the oncologist and measures on common problems previously reported for LTCS, related to cancer diagnosis and treatment, function, lifestyle, and emotional concerns, were collected from the patient. RESULTS: The mean age of our patients was 65.1 years at the time of the study and a median time without any antitumor treatment of 5.7 years. At the time of cancer diagnosis, 298 patients (85.9%) had at least one related chronic disease and 184 patients (53%) were retired. In addition, in 17.9% of those who continued working, income had been reduced. The incidence of health problems showed an increase during follow-up, even after 5 years, and required evaluation in an emergency department in 157 cases (45.3%). Regardless of age or sex, 239 patients (68.9%) had a significant decrease in sexual activity and 120 (34.6%) were diagnosed with clinical depression. CONCLUSIONS: LTCS are patients with significantly high socioeconomic, labor, sexual, health, and psychological problems, 5 years after completion of cancer treatment, especially in older survivors. IMPLICATIONS FOR CANCER SURVIVOR: Common concerns of LTCS were identified and are consistent across many countries. It is important to realize that even 5 or so years following treatment, both medical and non-medical problems can exist and may need attention by an expert.

Breast cancer patient experiences through a journey map: A qualitative study.

BACKGROUND: Breast cancer is one of the most prevalent diseases in women. Prevention and treatments have lowered mortality; nevertheless, the impact of the diagnosis and treatment continue to impact all aspects of patients' lives (physical, emotional, cognitive, social, and spiritual). OBJECTIVE: This study seeks to explore the experiences of the different stages women with breast cancer go through by means of a patient journey. METHODS: This is a qualitative study in which 21 women with breast cancer or survivors were interviewed. Participants were recruited at 9 large hospitals in Spain and intentional sampling methods were applied. Data were collected using a semi-structured interview that was elaborated with the help of medical oncologists, nurses, and psycho-oncologists. Data were processed by adopting a thematic analysis approach. RESULTS: The diagnosis and treatment of breast cancer entails a radical change in patients' day-to-day that linger in the mid-term. Seven stages have been defined that correspond to the different medical processes: diagnosis/unmasking stage, surgery/cleaning out, chemotherapy/loss of identity, radiotherapy/transition to normality, follow-up care/the "new" day-to-day, relapse/starting over, and metastatic/time-limited chronic breast cancer. The most relevant aspects of each are highlighted, as are the various cross-sectional aspects that manifest throughout the entire patient journey. CONCLUSIONS: Comprehending patients' experiences in depth facilitates the detection of situations of risk and helps to identify key moments when more precise information should be offered. Similarly, preparing the women for the process they must confront and for the sequelae of medical treatments would contribute to decreasing their uncertainty and concern, and to improving their quality-of-life.

Prediction of quality of life in early breast cancer upon completion of adjuvant chemotherapy.

Quality of life (QoL) is a complex, ordinal endpoint with multiple conditioning factors. A predictive model of QoL after adjuvant chemotherapy can support decision making or the communication of information about the range of treatment options available. Patients with localized breast cancer (n = 219) were prospectively recruited at 17 centers. Participants completed the EORTC QLQ-C30 questionnaire. The primary aim was to predict health status upon completion of adjuvant chemotherapy adjusted for multiple covariates. We developed a Bayesian model with six covariates (chemotherapy regimen, TNM stage, axillary lymph node dissection, perceived risk of recurrence, age, type of surgery, and baseline EORTC scores). This model allows both prediction and causal inference. The patients with mastectomy reported a discrete decline on all QoL scores. The effect of surgery depended on the interaction with age. Women with ages on either end of the range displayed worse scores, especially with mastectomy. The perceived risk of recurrence had a striking effect on health status. In conclusion, we have developed a predictive model of health status in patients with early breast cancer based on the individual's profile.

Angiogenesis as a therapeutic target in urothelial carcinoma.

In the last few years, angiogenesis has confirmed its critical role in the development of malignant neoplasms. Antiangiogenic drugs, mainly bevacizumab, sorafenib, or sunitinib, are currently approved in a wide number of tumor types, such as breast, colorectal, liver, or kidney cancer, and have changed dramatically the evolution of our patients. Unfortunately, in urothelial carcinoma, which is a very common neoplasm, antiangiogenic agents are still in a very preliminary phase of clinical research. In this study, we focus on the biological basis of angiogenesis in urothelial tumors, its influence in the prognosis of these malignancies, and the available evidence about the use of antiangiogenic drugs in urothelial carcinoma.

Ascertaining breast cancer patient experiences through a journey map: A qualitative study protocol.

BACKGROUND: The current cancer care system must be improved if we are to have in-depth knowledge about breast cancer patients' experiences throughout all the stages of their disease. AIM: This study seeks to describe breast cancer patients' experience over the course of the various stages of illness by means of a journey model. METHODS: This is a qualitative descriptive study. Individual, semi-structured interviews will be administered to women with breast cancer and breast cancer survivors. Patients will be recruited from nine large hospitals in Spain and intentional sampling will be used. Data will be collected by means of a semi-structured interview that was elaborated with the help of medical oncologists, nurses, and psycho-oncologists. Data will be processed adopting a thematic analysis approach. DISCUSSION: The outcomes of this study will afford new insights into breast cancer patients' experiences, providing guidance to improve the care given to these individuals. This protocol aims to describe the journey of patients with breast cancer through the healthcare system to establish baseline data that will serve as the basis for the development and implementation of a patient-centered, evidence-based clinical pathway.

Effects of pessimism, depression, fatigue, and pain on functional health-related quality of life in patients with resected non-advanced breast cancer.

INTRODUCTION: The aim was to analyze the effects of pessimism, depression, fatigue, and pain on functional health-related quality of life (HRQoL) in patients with resected, non-advanced breast cancer. METHODS: A prospective, multicenter study was conducted in 440 breast cancer patients. They completed the Brief Symptom Inventory (BSI), the European Organization for Research and Treatment of Cancer QoL-Questionnaire-Core-30 (EORTC-QLQ-C30), and the Revised Life Orientation Test (LOT-R). RESULTS: Prevalence rates of pessimism and depression were 23.3% and 40.0%, respectively. Fatigue and pain were the most common symptoms, 8.8% and 4.2%, respectively. Patients without a partner were more pessimistic that partnered ones; those with a lower level of education and subjects without a partner exhibited more depression. Depression was a major factor that proved to have the greatest explanatory power for HRQoL (physical, role, emotional, cognitive, and social functioning) and global health status (R2 range: 0.13 to 0.39). Of the five domains, fatigue had a significant effect on four and pain, on two. CONCLUSION: This study reveals the impact of depression and pessimism on physical, psychological, social, and quality-of-life aspects and the importance of evaluating them in patients who are going to initiate adjuvant chemotherapy for breast cancer.