AbstractPoorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) are a rare neoplasm with a bleak prognosis. Currently there are little prospective data available for optimal treatment. This review discusses the current available regimens and the future direction for the treatment of GEPNECs. Treatment plans for GEPNECs are often adapted from those devised for small cell lung cancer; however, differences in these malignancies exist, and GEPNECs require their own treatment paradigms. As such, current first‐line treatment for GEPNECs is platinum‐based chemotherapy with etoposide. Studies show that response rate and overall survival remain comparable between cisplatin and carboplatin versus etoposide and irinotecan; however, prognosis remains poor, and more efficacious therapy is needed to treat this malignancy. Additional first‐line and second‐line treatment options beyond platinum‐based chemotherapy have also been investigated and may offer further treatment options, but again with suboptimal outcomes. Recent U.S. Food and Drug Administration approval of peptide receptor radionuclide therapy in low‐ and intermediate‐grade neuroendocrine tumors may open the door for further research in its usefulness in GEPNECs. Additionally, the availability of checkpoint inhibitors lends promise to the treatment of GEPNECs. This review highlights the lack of large, prospective studies that focus on the treatment of GEPNECs. There is a need for randomized control trials to elucidate optimal treatment regimens specific to this malignancy.Implications for Practice.There are limited data available for the treatment of poorly differentiated gastroenteropancreatic neuroendocrine carcinomas (GEPNECs) because of the rarity of this malignancy. Much of the treatment regimens used in practice today come from research in small cell lung cancer. Given the poor prognosis of GEPNECs, it is necessary to have treatment paradigms specific to this malignancy. The aim of this literature review is to summarize the available first‐ and second‐line GEPNEC therapy, outline future treatments, and highlight the vast gap in the literature.
Brain Metastases and Place of Antiangiogenic Therapies in Alveolar Soft Part Sarcoma: A Retrospective Analysis of the French Sarcoma Group
AbstractBackground.Alveolar soft part sarcoma (ASPS) is a rare sarcoma characterized by a slow evolution, brain metastasis (BM), and resistance to doxorubicin. Antiangiogenic therapies (AAT) have shown clinical activity, but little is known about the optimal therapeutic strategy, specifically considering BM.Subjects, Materials, and Methods.We performed a retrospective analysis of all patients with ASPS treated in three referral centers of the French Sarcoma Group. We aimed to describe factors associated with overall survival (OS) and the impact of BM on outcome of patients treated by AAT.Results.We identified 75 patients between 1971 and 2012 (median age = 23, range: 5–96 years). Median follow‐up was 74 months. Patients with localized (n = 44, 59%) and metastatic (n = 31, 41%) diseases had a 10‐year OS of 69% and 25%, respectively. Only surgical incomplete resection was associated with shorter OS in localized disease (hazard ratio [HR] = 5.2, 95% confidence interval [CI] 1.2–22.4, p = .02). Fifty‐two (69%) patients developed lung metastasis (LM; baseline: n = 31, [41%]; de novo: n = 21, [28%]). Thirteen patients developed BM, all occurring after LM. Tumor size ≥5 cm was associated with poorer BM‐free survival (HR = 8.4, 95% CI 2.1–33.9, p = .002). Median OS post‐BM was 17 months (95% CI 15 to not assessable). Overall, 12 patients were treated with AAT (sunitinib n = 10): 5 patients had BM and achieved poor outcomes compared with patients without, with median progression‐free‐survivals of 2 versus 11 months, respectively.Conclusion.Baseline larger tumors were associated with increased risk of brain metastasis in patients with ASPS. Patients with BM seem to have little benefit from AAT, suggesting the need to develop antineoplastic agents with high central nervous system penetrance in this setting.Implications for Practice.Alveolar soft part sarcoma (ASPS) is an extremely rare subtype of sarcoma that is particularly resistant to conventional therapies. Antiangiogenic therapies (AAT) have shown promising results. However, patients with ASPS still die of tumor evolution. This study highlights the prognostic shift induced by brain metastasis (BM), identifying this event as a major contributor to the death of patients with ASPS, and observes a striking lack of effectiveness of AAT in patients who had previously developed BM. This observation is of interest for the therapeutic development in ASPS, highlighting the need to develop strategies dedicated to BM, such as radiosurgery or high‐central nervous system penetrance tyrosine kinase inhibitors.
AbstractCheckpoint inhibitors such as pembrolizumab, an anti‐PD‐1 monoclonal antibody, are a promising new category of oncological therapeutics, associated with a higher risk of immune‐related adverse events including dermatological, autoimmune and endocrine sequelae. Here, we present a case of a woman 76 years of age with stage IV lung adenocarcinoma who developed a severe and steroid‐refractory lichenoid dermatitis associated with pruritus on pembrolizumab. This eruption resolved completely with a short course of oral cyclosporine. Cyclosporine is a promising and effective treatment option for checkpoint inhibitor‐related severe cutaneous eruptions.
Current Pharmacotherapy Does Not Improve Severity of Hypoactive Delirium in Patients with Advanced Cancer: Pharmacological Audit Study of Safety and Efficacy in Real World (Phase‐R)
AbstractBackground.Pharmacotherapy is generally recommended to treat patients with delirium. We sought to describe the current practice, effectiveness, and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer, and to explore predictors of the deterioration of delirium symptoms after starting pharmacotherapy.Subjects, Materials, and Methods.We included data of patients with advanced cancer who were diagnosed with hypoactive delirium and received pharmacotherapy for treatment of delirium. This was a pharmacovigilance study characterized by prospective registries and systematic data‐recording using internet technology, conducted among 38 palliative care teams and/or units. The severity of delirium and other outcomes were assessed using established measures at days 0 (T0), 3 (T1), and 7 (T2).Results.Available data were obtained from 218 patients. The most frequently used agent was haloperidol (37%). A total of 67 and 42 patients (31% and 19%) had died or discontinued pharmacotherapy by T1 and T2, respectively. Delirium symptoms deteriorated between T0 and T1, but this trend did not reach statistical significance. The most prevalent adverse event was sedation (9%). Delirium severity worsened after starting pharmacotherapy in 121 patients (56%) at T1. In patients whose death was expected within a few days and those with delirium caused by organ failure, symptoms of delirium were significantly more likely to deteriorate after starting pharmacotherapy.Conclusion.Current pharmacotherapy for hypoactive delirium in patients with advanced cancer is not recommended, especially in those whose death is expected within a few days and in those with delirium caused by organ failure.Implications for Practice.Delirium is common among patients with advanced cancer, and hypoactive delirium is the dominant motor subtype in the palliative care setting. Pharmacotherapy is recommended and regularly used to treat delirium. This article describes the effectiveness and adverse effects of pharmacotherapy for hypoactive delirium in patients with advanced cancer. The findings of this study do not support the use of pharmacotherapy for treatment of hypoactive delirium in the palliative care setting. Pharmacotherapy should especially be avoided in patients whose death is expected within a few days and in those with delirium caused by organ failure.
Treatment Patterns and Clinical Outcomes in Advanced Lung Neuroendocrine Tumors in Real‐World Settings: A Multicenter Retrospective Chart Review Study
AbstractBackground.Using data from four tertiary referral centers in the U.S., we assessed real‐world treatment patterns and clinical outcomes of patients with advanced lung neuroendocrine tumors (NETs).Subjects, Materials, and Methods.We performed a retrospective chart review of adult patients with locally advanced/metastatic (typical/atypical) lung NETs treated between July 2011 and December 2014. Index date was histologically confirmed typical/atypical carcinoid tumor diagnosis date. Data included baseline characteristics, treatment patterns, progression, death, and lung NET‐related health care resource use from index date through last contact/death. Time to treatment discontinuation and first progression, time from first to second progression, and overall survival (OS) were estimated using Kaplan‐Meier analysis.Results.We identified 83 patients; 19 (23%) had functional NET. First‐line treatments included somatostatin analogs (SSAs) alone (56%) or in combination with other therapies (6%), cytotoxic chemotherapy (20%), external beam radiation therapy (EBRT) (9%), liver‐directed therapy (LDT) (4%), and everolimus/other (5%). Sixty patients had second‐line therapy including SSA alone (18%) or in combination (40%), cytotoxic chemotherapy (17%), everolimus (12%), LDT (7%), EBRT (3%), and other treatments (3%). Median time (months) to first‐line discontinuation were as follows: SSAs, 43.3; cytotoxic chemotherapy, 3.6. Overall median time (months) to investigator‐assessed progression following treatment initiation was 12.4. Median OS (months) following treatment initiation was 66.4 for all patients and 81.5 for patients receiving SSAs.Conclusion.SSAs, alone and in combination, are common treatments for advanced lung NETs. Patients have additional treatment options and relatively long survival compared with patients with other advanced cancers. Treatment pattern assessment following approval of newer treatments is needed.Implications for Practice.Somatostatin analogs (SSAs), cytotoxic chemotherapy, EBRT, liver‐directed therapy, and targeted therapies are common treatments for locally advanced/metastatic (typical/atypical) lung neuroendocrine tumors (NETs). SSAs alone or in combination with other treatment modalities were the most common first‐ and second‐line therapy, followed by cytotoxic chemotherapy. Patients continued treatment with SSAs long‐term with median treatment duration of 43 months. Median overall survival was 66 months following initiation of first‐line therapy for all patients. Treatment pattern assessment beyond the time period of this study is needed given recent U.S. Food and Drug Administration approvals for additional treatments for lung NETs that will likely be incorporated in the treatment landscape.
AbstractBackground.Thymic atypical carcinoid (TAC) is a rare thymic neuroendocrine tumor that originates in the neuroendocrine system and lacks a standardized treatment. The combination of capecitabine (CAP) and temozolomide (TEM) is associated with an extremely high and long‐lasting response rate in patients with metastatic pancreatic neuroendocrine tumors. However, there is little evidence showing that the CAPTEM regimen is effective for TAC. For patients with unresectable or metastatic atypical carcinoid of the thymus, few treatment options are available, and the treatment efficacy is not satisfactory. To explore the efficacy and safety of the CAPTEM regimen against TAC, we conducted a retrospective review.Patients and Methods.A total of nine patients with advanced atypical carcinoid of the thymus in the China‐Japan Friendship Hospital were treated with capecitabine (750 mg/m2 twice daily, days 1–14) and temozolomide (200 mg/m2 once daily, days 10–14) every 28 days between 2014 and 2018. The disease control rate (DCR), progression‐free survival (PFS), and adverse effects after treatment were analyzed. The DCR was calculated by RECIST version 1.1. Progression‐free survival was calculated by the Kaplan‐Meier survival method.Results.A total of nine patients (six male and three female) were included. The median age at CAPTEM initiation was 50 years (range, 26–58). The median number of CAPTEM cycles was 8 (range, 3–23). The DCR was 89% (8/9), with eight patients achieving stable disease. Only one patient (11%) showed progressive disease. The median PFS was 8 months. Because we applied vitamin B6 and ondansetron before administering the drugs, the side effects of this regimen were very small. Adverse reactions were all below grade 3 and included myelosuppression and digestive tract reaction.Conclusion.Our results suggest that the CAPTEM regimen may be effective and well tolerated for the treatment of TAC. More evidence is needed to validate the effectiveness of this regimen.Implications for Practice.Capecitabine and temozolomide regimen is effective and well tolerated in patients with advanced thymic atypical carcinoid.
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