RESUMO
The novel anti-mitotic based tumor treating fields (TTFields) is FDA approved for recurrent glioblastoma. Recently the phase III upfront trial combining the Novo TTF-100A device, called Optune, with temozolomide following concurrent radiation therapy and chemotherapy, demonstrated improvement in survival. Wider use of this novel therapy is expected. The most common adverse event is dermatologic, which dominates compared to the next most frequently observed adverse event of headaches, the incidence of which was even in both arms in the phase III registration trial for recurrent glioblastoma. Our case review outlines the presentation, treatment, and outcome of representative patients using TTFields. In summary, preventative strategies to inform and educate patients and operators can prevent many of these dermatological events. Skin toxicity in the setting of concurrent use of TTFields with other therapies such as bevacizumab is an unknown and will need to be closely followed.
Assuntos
Neoplasias Encefálicas/terapia , Terapia por Estimulação Elétrica/efeitos adversos , Glioblastoma/terapia , Dermatopatias/etiologia , Adulto , Terapia Combinada/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dermatopatias/patologiaRESUMO
OBJECTIVE: To report on invasive aspergillosis infection in an immunocompetent adult after a near-drowning event, which allowed this pathogen to easily gain access to the human respiratory system and result in rapid, severe infection. CASE SUMMARY: A 51-year-old female developed severe pneumonia after a near-drowning accident. Two days after admission, a bronchial alveolar lavage (BAL) was performed and was positive for Aspergillus fumigatus. After a 30-day hospital course, multiple antifungals, and various routes of administration, the patient expired. DISCUSSION:: Pneumonia is particularly common because of the aspiration of contaminated water. Whereas pneumococci, staphylococci, and Gram-negative bacteria are all common pathogens for this type of infection, fungi such as Aspergillus spp can also be involved and may be life threatening. Typically, these cases are reported in individuals with an immunodeficiency such as from receipt of myelosuppressive chemotherapy, bone marrow transplants, or lung transplants. Despite initiation of an appropriate empirical antifungal regimen, the rapid recovery of A fumigatus from pulmonary alveolar lavage and BAL samples as well as extremely elevated levels of galactomannan and (1â3)-ß-D glucan may have indicated an invasive fungal infection (IFI). CONCLUSION:: IFIs are uncommon in immunocompetent adults, but in the event of a near-drowning accident, environmental fungi can gain access to the human respiratory system and result in rapid, severe infection. Based on this case and the others described, it appears that near-drowning patients need an early initial evaluation for IFI.
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Liposomal daunorubicin/cytarabine (CPX-351) gained FDA approval for secondary AML after demonstrating improved outcomes over daunorubicin and cytarabine (7 + 3). A number of study limitations prompted a comparison of safety/efficacy of CPX-351 against regimens containing a purine analogue and high-dose cytarabine (HIDAC). This retrospective study compared complete response rates with/without count recovery (CR/CRi) between HIDAC-based regimens and CPX-351 in 169 patients with newly diagnosed sAML. The CR/CRi rate was 62.7% in the HIDAC-based therapy arm vs. 47.9% in the CPX-351 arm (p = 0.002 [one-sided for non-inferiority]). Median time to absolute neutrophil and platelet count recovery was shorter after HIDAC-based therapy (18 and 23 days, respectively) compared to CPX-351 (36 and 38 days; p < 0.001). Median overall survival was 9.8 months in the HIDAC-based group and 9.14 months in the CPX-351 group. 30-day mortality was greater with CPX-351 (8.5%) compared to HIDAC-based (1.3%; p = 0.039). These results reveal comparable efficacy and favorable safety with HIDAC-based regimens.
Assuntos
Citarabina , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/uso terapêutico , Daunorrubicina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Estudos RetrospectivosRESUMO
BACKGROUND/AIM: Combination nab-paclitaxel/gemcitabine (AG) is superior to gemcitabine in patients with metastatic pancreatic cancer (PC). There are limited data for AG in borderline resectable (BR) or locally advanced pancreatic cancer (LAPC). Herein, we report our experience with neoadjuvant AG for BR/LAPC in patients ineligible for FOLFIRINOX. PATIENTS AND METHODS: This retrospective series, included patients with BR/LAPC who received AG as neoadjuvant therapy for 3-4 months followed by radiation, then re-evaluation for surgery. RESULTS: Between 10/2013-2/2018, 32 patients (22 BR, 10 LAPC) were treated with this approach. Median age was 70 years. Nine patients were converted to resectability by imaging; six had R0 resections (19%), five (16%) achieved a partial response and 24 (75%) had stable disease. CONCLUSION: In this small series, the R0 resection rate and response rate were 19% and 16% respectively. These data suggest that neoadjuvant AG may be an alternate option for patients ineligible for FOLFIRINOX.
Assuntos
Adenocarcinoma/tratamento farmacológico , Albuminas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Desoxicitidina/análogos & derivados , Terapia Neoadjuvante/métodos , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adenocarcinoma/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
Background: Individuals with cancer are at an increased risk of venous thromboembolism (VTE). There is a continued increased risk of recurrent VTE after the initial event as well as increased bleed risk related to VTE treatment. Objectives: This study sought to observe the incidence of recurrent VTE, major bleeding, and death in a geriatric oncology population during treatment for a cancer-associated VTE. Methods: We utilized an insurance claims database of Medicare Advantage beneficiaries 65 and older. The index VTE was identified and individuals were followed up to 180 days to observe an outcome event. Treatment groups were classified among those receiving warfarin, low-molecular weight heparins (LMWH), vena cava (VC) filters with or without anticoagulation, or no treatment. Treatment groups were compared on baseline demographic and clinical characteristics and an inverse probability of treatment weight was used to balance these factors between the groups. A competing risks, time-to-event analysis was performed including treatment only models as well as adjusted models with additional covariates. Causespecific hazards ratios (HRs) and their 95% confidence intervals were reported. Results: Treatment groups differed on baseline variables including age, comorbidities, and tumor sites. After balancing the treatment groups on baseline characteristics, those receiving LMWHs had no difference in recurrent VTE compared to warfarin but had less than half the risk of major bleeding (HR=0.48 [0.27-0.85]). Those receiving VC filters had increased risk of all outcome events relative to warfarin. Conclusions: Patients over the age of 65 with cancer are at a high risk of experiencing recurrent VTE and major bleeding during treatment for a cancer-associated VTE. These results are consistent with United States guidelines which recommend LMWHs over warfarin for treatment and secondary prevention of VTE.
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Deregulation of the phosphatidylinositol 3-kinase (PI3K) pathway is central to many human malignancies while normal cell proliferation requires pathway functionality. Although inhibitors of the PI3K pathway are in clinical trials or approved for therapy, an understanding of the functional activities of pathway members in specific malignancies is needed. In lung cancers, the PI3K pathway is often aberrantly activated by mutation of genes encoding EGFR, KRAS, and PIK3CA proteins. We sought to understand whether class IA PI3K enzymes represent rational therapeutic targets in cells of non-squamous lung cancers by exploring pharmacological and genetic inhibitors of PI3K enzymes in a non-small cell lung cancer (NSCLC) cell line system. We found that class IA PI3K enzymes were expressed in all cell lines tested, but treatment of NSCLC lines with isoform-selective inhibitors (A66, TGX-221, CAL-101 and IC488743) had little effect on cell proliferation or prolonged inhibition of AKT activity. Inhibitory pharmacokinetic and pharmacodynamic responses were observed using these agents at non-isoform selective concentrations and with the pan-class I (ZSTK474) agent. Response to pharmacological inhibition suggested that PI3K isoforms may functionally compensate for one another thus limiting efficacy of single agent treatment. However, combination of ZSTK474 and an EGFR inhibitor (erlotinib) in NSCLC resistant to each single agent reduced cellular proliferation. These studies uncovered unanticipated cellular responses to PI3K isoform inhibition in NSCLC that does not correlate with PI3K mutations, suggesting that patients bearing tumors with wildtype EGFR and KRAS are unlikely to benefit from inhibitors of single isoforms but may respond to pan-isoform inhibition.