Characterization and Management of Adverse Reactions in Patients With Advanced Endometrial Cancer Receiving Lenvatinib Plus Pembrolizumab.

BACKGROUND: Lenvatinib plus pembrolizumab significantly improved efficacy compared with chemotherapy in patients with advanced endometrial cancer (aEC) regardless of microsatellite instability status or histologic subtype, who had disease progression following prior platinum-based therapy, in Study-309/KEYNOTE-775. The safety profile of the combination was generally consistent with that of each monotherapy drug and of the combination in patients with endometrial cancer and other solid tumors. Given the medical complexity of patients with aEC, this paper aims to characterize key adverse reactions (ARs) of the combination treatment and review management strategies, providing a guide for AR management to maximize anticancer benefits and minimize treatment discontinuation. MATERIALS AND METHODS: In Study-309/KEYNOTE-775, patients received lenvatinib (20 mg orally once daily) plus pembrolizumab (200 mg intravenously every 3 weeks) or chemotherapy (doxorubicin or paclitaxel). The incidence and median time to the first onset of ARs, dose modifications, and concomitant medications are described. Key ARs characterized include hypothyroidism, hypertension, fatigue, diarrhea, musculoskeletal disorders, nausea, decreased appetite, vomiting, stomatitis, weight decreased, proteinuria, and palmar-plantar erythrodysesthesia syndrome. RESULTS: As expected, the most common any-grade key ARs included: hypothyroidism, hypertension, fatigue, diarrhea, and musculoskeletal disorders. Grades 3-4 key ARs with incidence ≥10% included: hypertension, fatigue, and weight decreased. Key ARs first occurred within approximately 3 months of treatment initiation. AR management strategies consistent with the prescribing information and the study protocol are discussed. CONCLUSION: Successful AR management strategies for lenvatinib plus pembrolizumab include education of the patient and entire treatment team, preventative measures and close monitoring, and judicious use of dose modifications and concomitant medications. CLINICALTRIALS.GOV ID: NCT03517449.

Impact of COVID-19 pandemic among patients with lung and head and neck cancer assisted in a public cancer center in Brazil.

BACKGROUND: There is no updated national data regarding the real impact of the COVID-19 pandemic on delaying diagnosis and treatment among patients with lung, and head, and neck cancers in Brazil. This study aimed to analyze the COVID-19 pandemic impact on cancer diagnosis and clinical outcomes among lung, head, and neck cancer patients assisted in a tertiary cancer center in Southeastern Brazil, as well as to analyze these patients' pretreatment clinical features. METHODS: Retrospective cohort of patients with lung or head and neck cancer assisted in a tertiary cancer center in southeastern Brazil between January/2019 and December/2021. To assess statistical differences among groups [i.e., cohort 2019 versus (vs.) 2020 and 2019 vs. 2021] chi-square test was used with a 5% significance level and 90% power for sample size calculation. Differences among baseline clinical features and sociodemographic characteristics were evaluated either by T-test for two samples or Fisher's or Pearson's chi-square test (for quantitative or qualitative variables). All utilized tests had a 5% significance level. RESULTS: Six hundred fifty-two patients were included, 332 with lung and 320 with head and neck cancer; it was observed a significant decrease in oncologic treatment recommendations and increase in palliative care recommendation for patients with lung cancer, despite similar stages at diagnosis. During the COVID-19 pandemic, more pain symptoms were reported at the first Oncology assessment for patients with head and neck cancer (p < 0.05). Compared to 2019, head and neck cancer patients diagnosed in 2021 presented a worse initial performance status (p = 0.008). There was a statistically significant increase in survival for patients diagnosed with head and neck cancer in 2021 when compared to 2019 (p = 0.003). CONCLUSIONS: This research highlights low survival rates for patients with lung and head and neck cancer in Brazil, even before the pandemic started, as consequence of advanced diseases at diagnosis at the public health system and clinical degrading features. Additionally, there was an increase incidence in both lung cancer and head and neck cancer despite no differences in clinical stage. This reflects how fragile is the public healthcare system even before facing an acute public health crisis such as the COVID-19 pandemic. Yet, the total impact on public health may follow for many years.

Real world challenges and disparities in the systemic treatment of ovarian cancer.

Ovarian cancer (OC) is a global health problem, and the mortality-to-incidence ratio is expected to increase, especially in low- and middle-income countries. These regions face disparities in access to OC care, including lack of awareness, limited access to genetic and tumor testing, paucity of surgical expertise, time to approval of novel therapeutics, and treatment costs. By addressing these inequities, the core aim of this paper is to promote action through collaboration in order to overcome these barriers and promote health equity in OC management and treatment.

Management of endometrial cancer in Latin America: raising the standard of care and optimizing outcomes.

Molecular characterization of endometrial cancer is allowing for increased understanding of the natural history of tumors and paving a more solid pathway for novel therapies. It is becoming increasingly apparent that molecular classification is superior to histological classification in terms of reproducibility and prognostic discrimination. In particular, the Proactive Molecular Risk Classifier for Endometrial Cancer allows classification of endometrial cancer into groups very close to those determined by the Cancer Genome Atlas Research Network-that is, DNA polymerase epsilon-mutated, mismatch repair-deficient, p53 abnormal, and non-specific molecular profile tumors. The transition from the chemotherapy era to the age of targeted agents and immunotherapy, which started later in endometrial cancer than in many other tumor types, requires widespread availability of specialized pathology and access to novel agents. Likewise, surgical expertise and state-of-the-art radiotherapy modalities are required to ensure adequate care. Nevertheless, Latin American countries still face considerable barriers to implementation of international guidelines. As we witness the dawn of precision medicine as applied to endometrial cancer, we must make continued efforts towards improving the quality of care in this region. The current article discusses some of these challenges and possible solutions.

Tailoring Endometrial Cancer Treatment Based on Molecular Pathology: Current Status and Possible Impacts on Systemic and Local Treatment.

Endometrial cancer (EC) is a heterogeneous disease with a rising incidence worldwide. The understanding of its molecular pathways has evolved substantially since The Cancer Genome Atlas (TCGA) stratified endometrial cancer into four subgroups regarding molecular features: POLE ultra-mutated, microsatellite instability (MSI) hypermutated, copy-number high with TP53 mutations, and copy-number low with microsatellite stability, also known as nonspecific molecular subtype (NSMP). More recently, the International Federation of Gynecology and Obstetrics (FIGO) updated their staging classification to include information about POLE mutation and p53 status, as the prognosis differs according to these characteristics. Other biomarkers are being identified and their prognostic and predictive role in response to therapies are being evaluated. However, the incorporation of molecular aspects into treatment decision-making is challenging. This review explores the available data and future directions on tailoring treatment based on molecular subtypes, alongside the challenges associated with their testing.

Patient navigation (PN) support to timely access to radiotherapy in the Brazilian public health system.

PURPOSE: Patient navigation (PN) is a community-based service delivery intervention designed to promote access to timely diagnosis and treatment of cancer and other chronic diseases by eliminating barriers to integral care. Considering the complex difficulties in accessing treatment and the positive results of PN in high-income countries, our group decided to evaluate this tool to improve radiotherapy (RT) access in the public system in Brazil. PATIENTS AND METHODS: This pilot study took place in a public school hospital, with a historical cohort as the control arm. The primary endpoint was the time from histologic diagnosis and RT initiation among cancer patients receiving RT with curative intent in a PN program. The secondary objectives were the following time frames: referral to the first consultation by the RT team; first consultation up to RT beginning; RT beginning to RT end; referral to the end of RT and identifying/describing obstacles to the treatment; and assessing patient satisfaction with PN program. RESULTS: A total of 124 patients were included in the retrospective arm and 73 in the navigation arm. Most had the loco-regionally advanced disease from the esophagus, head/neck, and rectum. PN decreased the median time from the biopsy result to the beginning of RT from 108 to 74 days (p < 0.001). PN reduced the time between biopsy results and referral to RT (53 to 40.5 days, p = 0.011), between the referral and the first consultation in the RT (25 to 13 days, p < 0.001), and between the referral to the end of the RT (98 to 78 days, p < 0.003). CONCLUSIONS: Proper identification of barriers, especially in a low-resource setting, is mandatory to guide PN programs in LMICs. In an oncological context of socioeconomic vulnerability, PN is a financially viable and efficient tool to optimize access to timely RT.

Looking beyond carboplatin and paclitaxel for the treatment of advanced/recurrent endometrial cancer.

Endometrial cancer incidence and mortality are rising among all ethnic groups. Carboplatin plus paclitaxel is the established frontline treatment for advanced/recurrent disease; however, subsequent treatment with traditional cytotoxic chemotherapy is challenging. The molecular characterization of endometrial cancer has provided important insights into the biological drivers of carcinogenesis, which has allowed for the development of newer precision immunotherapies and targeted therapies, including pembrolizumab, dostarlimab, and lenvatinib. Until recently, platinum rechallenge was often considered at the time of recurrence, given the lack of other available therapeutic options; however, "platinum sensitivity" in endometrial cancer is subjective and largely based on expert opinion and/or practitioner experience. Small retrospective studies have tried to provide guidance on the utility of platinum rechallenge, but they are limited by variable patient characteristics and small sample sizes. The applicability of these retrospective studies to contemporary clinical practice is difficult in the setting of changing patient demographics, a better understanding of endometrial cancer drivers, and the recent approvals of immune checkpoint inhibitors and the combination of lenvatinib plus pembrolizumab in the second-line setting. The primary focus of this review is to distill the available data regarding platinum-doublet chemotherapy rechallenge and highlight recent pivotal developments in endometrial cancer treatment, as well as future directions.

Primary results from CECILIA, a global single-arm phase II study evaluating bevacizumab, carboplatin and paclitaxel for advanced cervical cancer.

OBJECTIVE: Adding bevacizumab to cisplatin-paclitaxel for advanced cervical cancer significantly improves overall and progression-free survival. We evaluated bevacizumab with a widely used carboplatin-paclitaxel backbone. METHODS: Patients with metastatic/recurrent/persistent cervical cancer not amenable to curative surgery and/or radiotherapy received 3-weekly bevacizumab 15 mg/kg, paclitaxel 175 mg/m2, and carboplatin AUC 5 until progression or unacceptable toxicity. Maintenance bevacizumab was allowed. Patients with ongoing bladder/rectal involvement, prior cobalt radiotherapy, a history of fistula/gastrointestinal perforation, or recent bowel resection/chemoradiation were excluded. The primary objective was to determine incidences of gastrointestinal perforation/fistula, gastrointestinal-vaginal fistula, and genitourinary fistula. RESULTS: Among 150 treated patients, disease at study entry was persistent in 21%, recurrent in 56%, and newly diagnosed metastatic in 23%. After 27.8 months' median follow-up, median bevacizumab duration was 6.7 months; 57% received maintenance bevacizumab. Seventeen patients (11.3%; 95% CI: 6.7-17.5%) experienced ≥1 perforation/fistula event: gastrointestinal perforation/fistula in 4.7% (1.9-9.4%), gastrointestinal-vaginal fistula in 4.0% (1.5-8.5%), and genitourinary fistula in 4.7% (1.9-9.4%). Of these, 16 were previously irradiated, several with ongoing radiation effects. The most common grade 3/4 adverse events were neutropenia (25%), anemia (19%), and hypertension (14%). Five patients (3%) had fatal adverse events. Objective response rate was 61% (95% CI: 52-69%), median progression-free survival was 10.9 (10.1-13.7) months, and median overall survival was 25.0 (20.9-30.4) months. CONCLUSIONS: Bevacizumab can be combined with carboplatin-paclitaxel in the CECILIA study population. The fistula/gastrointestinal perforation incidence is in line with GOG-0240; efficacy results are encouraging. TRIAL REGISTRATION NUMBER: NCT02467907 (ClinicalTrials.gov).

Systematic Review and Network Meta-Analysis of Bevacizumab Plus First-Line Topotecan-Paclitaxel or Cisplatin-Paclitaxel Versus Non-Bevacizumab-Containing Therapies in Persistent, Recurrent, or Metastatic Cervical Cancer.

OBJECTIVE: Despite advances in cervical cancer prevention and diagnosis, outcomes for patients given a diagnosis of advanced and recurrent disease are poor. In the GOG240 trial, the addition of bevacizumab to paclitaxel-topotecan or paclitaxel-cisplatin has been shown to prolong survival compared with paclitaxel-topotecan or paclitaxel-cisplatin in patients with persistent, recurrent, or metastatic disease. However, standards of care vary between regions and countries. The purpose of this systematic review and network meta-analysis was to enable a comparison between bevacizumab + chemotherapy with multiple monotherapy or combination chemotherapy regimens in the treatment for women with advanced, recurrent, or persistent cervical cancer. METHODS/MATERIALS: A systematic literature review was conducted to identify randomized or nonrandomized controlled trials of patients with recurrent, persistent, or metastatic cervical cancer published in English from 1999 to 2015. A feasibility study was performed to assess the heterogeneity of the trials, and a network meta-analysis was conducted. Fixed- and random-effects models were fitted to calculate the hazard ratio for overall survival (OS) for all pairwise comparisons and ranking of all interventions. RESULTS: Twenty-three studies (19 trials) met inclusion criteria and were included in the review. Sample sizes ranged from 69 to 452, and median patient age ranged from 45 to 53 years. There was a trend toward prolonged OS with cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab compared with all non-bevacizumab-containing therapies. Cisplatin-paclitaxel-bevacizumab had the highest probability of being the most efficacious compared with all regimens (68.1%), and cisplatin monotherapy had the lowest (0%). CONCLUSIONS: The results of this network meta-analysis show that bevacizumab in combination with paclitaxel-topotecan or paclitaxel-cisplatin is likely to prolong OS over other non-bevacizumab-containing chemotherapies (eg, paclitaxel-carboplatin), which were not included in the GOG240 trial. In patients with advanced, persistent, and recurrent cervical cancer, cisplatin-paclitaxel-bevacizumab and topotecan-paclitaxel-bevacizumab showed the highest efficacy in all regimens investigated in this analysis.

Barriers to Primary Debulking Surgery for Advanced Ovarian Cancer in Latin America.

Ovarian cancer is gynecologic tumor with particularly high mortality because it is usually diagnosed in advanced stages. In Latin America and the Caribbean, it is the eighth most common malignancy in women, with an estimated 18,000 new cases and 11,500 deaths annually. Standard of care for women diagnosed with advanced ovarian cancer (AOC) is primary cytoreductive surgery followed by systemic chemotherapy using a combination of paclitaxel plus carboplatin. To pursue upfront surgery, highly specialized and well-trained gynecologic oncologists are required, in addition with well-equipped hospitals. Neoadjuvant chemotherapy (NACT) has been gaining greater acceptance in the past decade for patients with AOC. Two phase III randomized clinical trials have demonstrated that NACT is noninferior to primary cytoreductive surgery for women with stages III and IV epithelial ovarian cancer, and since publication of these results, NACT is more commonly used. Apart from medical reasons of inoperability and unresectability, there may be nonmedical barriers to upfront debulking surgery in clinical practice. These barriers include inadequate expertise of the surgeon, inadequate resources, and/or barriers to access. The aim of this article was to discuss patterns of care and barriers to upfront ovarian debulking surgery, as well as a possible shift toward overuse of NACT as the primary approach for patients with AOC (stages III and IV) in Latin America.

Cervical cancer control in Latin America: A call to action.

Cervical cancer (CC) is second most common cause of cancer in Latin America and is a leading cause of cancer mortality among women. In 2015, an estimated 74,488 women will be diagnosed with CC in Latin America and 31,303 will die of the disease. CC mortality is projected to increase by 45% by 2030 despite human papillomavirus (HPV) vaccination and screening efforts. In this setting, the goal was of the current study was to examine CC control efforts in Latin America and identify deficiencies in these efforts that could be addressed to reduce CC incidence and mortality. The authors found that HPV vaccination has been introduced in the majority of Latin American countries, and there is now a need to monitor the success (or shortcomings) of these programs and to ensure that these programs are sustainable. This topic was also reviewed in light of emerging data demonstrating that visual inspection with acetic acid and HPV DNA testing without Papanicolaou tests have efficacy from a screening perspective and are good alternatives to cytology-based screening programs. Overall, there is a need to build capacity for CC control in Latin America and the best strategy will depend on the country/region and must be tailored to meet the needs of the population as well as available resources.

Patterns of Care and Outcome of Elderly Women Diagnosed With Cervical Cancer in the Developing World.

Scarce data exist about the impact of age in cervical cancer (CC) patients in the developing world. The objective of the current study was to examine the patterns of care and outcome of elderly patients treated in a developing country. Medical records of patients treated from 2006-2009 at the Brazilian National Cancer Institute were reviewed. Patients were divided between women 70 years or older and women younger than 70 years. The χ tests were used and odds ratios were calculated. Survival was examined using the Kaplan-Meier method. Single and multivariate Cox proportional hazards modeling were used. A total of 1482 patients were analyzed: 1339 patients younger than 70 years and 143 patients 70 years or older. A marked difference in treatment was noted, even after stratifying by disease stage. Only 21% of the older patients underwent surgical treatment compared with 27.6% of the younger. After adjusting for confounding variables, the hazard ratio for death from CC in the elderly was 1.05 (95% confidence interval, 0.81-1.36; P = 0.11). These results corroborate previous data from developed countries: elderly patients have more advanced disease at diagnosis, and age is an important factor in the allocation of treatment for patients with CC. Worse outcome seemed to be mainly the result of more advanced stage and treatment allocation rather than age itself.

Progress and remaining challenges for cancer control in Latin America and the Caribbean.

Cancer is one of the leading causes of mortality worldwide, and an increasing threat in low-income and middle-income countries. Our findings in the 2013 Commission in The Lancet Oncology showed several discrepancies between the cancer landscape in Latin America and more developed countries. We reported that funding for health care was a small percentage of national gross domestic product and the percentage of health-care funds diverted to cancer care was even lower. Funds, insurance coverage, doctors, health-care workers, resources, and equipment were also very inequitably distributed between and within countries. We reported that a scarcity of cancer registries hampered the design of credible cancer plans, including initiatives for primary prevention. When we were commissioned by The Lancet Oncology to write an update to our report, we were sceptical that we would uncover much change. To our surprise and gratification much progress has been made in this short time. We are pleased to highlight structural reforms in health-care systems, new programmes for disenfranchised populations, expansion of cancer registries and cancer plans, and implementation of policies to improve primary cancer prevention.

Phase 2 trial of erlotinib combined with cisplatin and radiotherapy in patients with locally advanced cervical cancer.

BACKGROUND: Cisplatin-based chemoradiation (CRT) is the standard treatment for patients with locally advanced cervical cancer. Epidermal growth factor receptor (EGFR) is frequently overexpressed in cervical cancer, and EGFR inhibition itself has antitumor effects and potentiates CRT. Results of a previous phase 1 trial of the EGFR inhibitor erlotinib combined with cisplatin-based CRT (E + CRT) recommended a phase 2 erlotinib dose of 150 mg/day. METHODS: Eligibility criteria included International Federation of Gynecology and Obstetrics stage IIB to IIIB epidermoid cervical cancer, no prior therapy, and an Eastern Cooperative Oncology Group performance status of 0 to 2. Patients received erlotinib at a dose of 150 mg/day 1 week before and in combination with cisplatin (40 mg/m(2) administered weekly for 5 cycles) and radiotherapy (4500 centigrays in 25 fractions), followed by brachytherapy (4 fractions at a dose of 600 centigrays weekly). RESULTS: A total of 36 patients completed treatment with E + CRT. The median duration of therapy was 77 days and the median follow-up period was 59.3 months. The therapy was well tolerated overall, and 34 patients (94.4%) achieved a complete response. The 2-year and 3-year cumulative overall and progression-free survival rates were 91.7% and 80.6% and 80% and 73.8%, respectively. CONCLUSIONS: Treatment with E + CRT appears to be safe and exerts significant activity against locally advanced cervical cancer. To the best of the authors' knowledge, this is the first study to date to demonstrate that a target agent has promising activity against locally advanced cervical cancer.

Comparison of adenocarcinoma (ACA) and squamous cell carcinoma (SCC) of the uterine cervix in a sub-optimally screened cohort: a population-based epidemiologic study of 51,842 women in Brazil.

BACKGROUND: Most cancers of the uterine cervix are SCC, but the relative and absolute incidence of ACA has risen in recent years, and ACA now accounts for approximately 20% of invasive cervical cancers in the screened populations worldwide. OBJECTIVE: To compare the epidemiological, clinical characteristics, and treatment outcomes of ACA with those of SCC of the cervix in a sub-optimally screened population. METHODS: Data from cervical cancer patients with SCC and ACA treated from 2000 through 2009 were obtained from the Brazilian Hospital Cancer Register databases. The summary odds ratios and chi-square tests were estimated. RESULTS: A total of 51,842 patients including 45,540 (87.8%) cases of SCC and 6302 (12.2%) of ACA were analyzed. Compared with the ACA patients, the SCC patients were younger and more frequently black and had a higher degree of illiteracy and alcohol and tobacco consumers. The tumor stage at the time of diagnosis was also significantly different between the two groups. However, initial therapeutic response and death rate after the first course of treatment were similar in both groups. CONCLUSIONS: Differences between ACA and SCC were observed for all demographic and clinical variables analyzed but not for responses to treatment and death at the end of the first course of treatment. Irrespective of the histological subtype, the quality of screening and treatment must be improved in developing countries, since initial therapeutic response of ACA and SCC is similar.

Fertility preservation in female cancer patients in Brazil: perceptions and attitudes of infertility specialists.

Objective: Fertility preservation is a priority in oncology for female cancer patients. However, there is a lack of communication between infertility specialists and oncologists. This study aimed to evaluate infertility specialists' perceptions and experiences regarding fertility preservation. Methods: Conduct an online survey to profile infertility specialists. Participants were infertility affiliated with the Brazilian Federation of Gynecology and Obstetrics Associations (FEBRASGO). The specialists received an online survey, which response rate were 30.9%, most of whom were in southern and southeastern. The survey consisted on 14 questions about the infertility specialists' location, techniques in clinical practice, treatment successful rate, patients idea, etc. Results: The average experience in human reproduction were 15.5 ± 10.2 years (mean ± standard deviation, range 1-40). Among reproductive-aged female cancer patients recommended for fertility preservation, 60.3 ± 28.8% (range 10-100%) underwent preservation procedures. Main barriers were cost (41%), oncologists' knowledge or acceptance (35%) and accessibility (9%). Most infertility specialists (58%) considered 40 years the limit for fertility preservation. Leukemia, lymphoma, breast and ovarian cancers were prioritized for fertility preservation, while lung, thyroid, gastric, and brain cancers were less relevant. Conclusion: This is the first Brazilian study about infertility specialists' perceptions on oncology patients access to fertility preservation. These patients primarily receive treatment in the public health system, while infertility specialists mainly work in the private healthcare. This healthcare mode is currently fragmented, but integrating these experts is enhancing patient access to fertility preservation. Studies on this topic are still warranted.

Clinical Trial Protocol for ROSELLA: a phase 3 study of relacorilant in combination with nab-paclitaxel versus nab-paclitaxel monotherapy in advanced platinum-resistant ovarian cancer.

BACKGROUND: Ovarian cancer has the highest mortality among gynecologic cancers, primarily because it typically is diagnosed at a late stage and because of the development of chemoresistance in recurrent disease. Improving outcomes in women with platinum-resistant ovarian cancer is a substantial unmet need. Activation of the glucocorticoid receptor (GR) by cortisol has been shown to suppress the apoptotic pathways used by cytotoxic agents, limiting their efficacy. Selective GR modulation may be able to counteract cortisol's antiapoptotic effects, enhancing chemotherapy's efficacy. A previous phase 2 study has shown that adding intermittently dosed relacorilant, a selective GR modulator, to nab-paclitaxel improved outcomes, including progression-free survival (PFS) and overall survival (OS), with minimal added toxicity, in women with recurrent platinum-resistant ovarian cancer. The ROSELLA study aims to confirm and expand on these findings in a larger population. METHODS: ROSELLA is a phase 3, randomized, 2-arm, open-label, global multicenter study in women with recurrent, platinum-resistant, high-grade serous epithelial ovarian, primary peritoneal, or fallopian tube cancer. Eligible participants have received 1 to 3 lines of prior systemic anticancer therapy, including ≥1 prior line of platinum therapy and prior treatment with bevacizumab, with documented progressive disease or intolerance to the most recent therapy. There is no biomarker-based requirement for participant selection. Participants are randomized 1:1 to receive intermittently dosed relacorilant in combination with nab-paclitaxel or nab-paclitaxel monotherapy. The study's primary efficacy endpoint is PFS as assessed by blinded independent central review. Secondary efficacy endpoints include OS, investigator-assessed PFS, objective response rate, best overall response, duration of response, clinical benefit rate at 24 weeks, and cancer antigen 125 response. The study is also evaluating safety and patient-reported outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05257408; European Union Drug Regulating Authorities Clinical Trials Database Identifier: 2022-000662-18.

The adolescent and young adult with cancer: state of the art--epithelial cancer.

The adolescent and young adult (AYA) is defined as a patient of 15 to 39 years of age at initial cancer diagnosis, and this group has particular medical needs and age-related issues. Excluding violent deaths, cancer is the leading cause of death among the AYA population. Lymphomas, melanoma, testicular cancer, female genital tract malignancies, thyroid cancer, bone and soft tissue sarcomas, leukemias, central nervous system tumors, breast cancer, and nongonadal germ cell tumors account for 95 % of the cancers in this group. Among those, the epithelial cancer of AYA comprehends the minimum amount and its incidence rates tend to increase with age. This review presents information about epidemiology, biologic peculiarities, as well as standard treatment strategies for epithelial cancers in AYA.

First-line paclitaxel and carboplatin in persistent/recurrent or advanced cervical cancer: a retrospective analysis of patients treated at Brazilian National Cancer Institute.

OBJECTIVE: Cervical cancer represents the third most commonly diagnosed cancer and the fourth cause of cancer death in women worldwide. In the palliative scenario, the combination of paclitaxel and cisplatin is widely used. Carboplatin is also an active agent in cervical cancer, and its association with paclitaxel could represent a well-tolerated, less toxic, and effective therapeutic option. The objective of this study was to evaluate response rate, progression-free survival, overall survival, and toxicity of carboplatin and paclitaxel in first palliative line for cervical cancer. METHODS: A retrospective search of database at Brazilian National Cancer Institute was performed, and all patients with persistent/recurrent and advanced cervical cancer treated with paclitaxel and carboplatin in first palliative line, between August 2008 and January 2010, were included. RESULTS: A total of 153 women were enrolled. Objective responses were documented in 34.6% (5.2% of complete responses and 29.4% of partial responses). With a median follow-up of 27.8 months, the median progression-free survival was 5.2 months, and the median overall survival was 10.63 months. The most common toxicity was myelosuppression: grades 3 and 4 anemia, neutropenia, and thrombocytopenia observed in 43.0%, 17.8%, and 9.2% of the cases, respectively. Neurotoxicity was presented by 30.7% of the patients. Renal toxicity was detected in 21.9% of the patients, but only 4.0% were grade 3, and none were grade 4. CONCLUSIONS: This retrospective study has demonstrated that paclitaxel-carboplatin is an active and well-tolerated regimen for the treatment of advanced cervical cancer.