RESUMO
As the world embarks on mass vaccination for COVID-19, we are beginning to encounter unintended dilemmas in imaging oncology patients; particularly with regards to FDG PET/CT. In some cases, vaccine-related lymphadenopathy and FDG uptake on PET/CT can mimic cancer and lead to confounding imaging results. These cases where findings overlap with cancer pose a significant dilemma for diagnostic purposes, follow-up, and management leading to possible treatment delays, unnecessary repeat imaging and sampling, and patient anxiety. These cases can largely be avoided by optimal coordination between vaccination and planned imaging as well as preemptive selection of vaccine administration site. This coordination hinges on patient, oncologist, and radiologists' awareness of this issue and collaboration. Through close communication and patient education, we believe this will eliminate significant challenges for our oncology patients as we strive to end this pandemic.
Assuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/prevenção & controle , Linfadenopatia/diagnóstico , Neoplasias/diagnóstico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/normas , Vacinação/efeitos adversos , COVID-19/virologia , Diagnóstico Diferencial , Progressão da Doença , Fluordesoxiglucose F18/metabolismo , Humanos , Linfadenopatia/induzido quimicamente , Linfadenopatia/diagnóstico por imagem , Neoplasias/induzido quimicamente , Neoplasias/diagnóstico por imagem , Compostos Radiofarmacêuticos/metabolismo , SARS-CoV-2/isolamento & purificaçãoAssuntos
Regulação Leucêmica da Expressão Gênica , Subunidade alfa de Receptor de Interleucina-2/análise , Leucemia Mieloide Aguda/genética , Proteínas de Neoplasias/análise , Células-Tronco Neoplásicas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Duplicação Gênica , Transplante de Células-Tronco Hematopoéticas , Humanos , Subunidade alfa de Receptor de Interleucina-2/biossíntese , Subunidade alfa de Receptor de Interleucina-2/genética , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Estudos Retrospectivos , Sequências de Repetição em Tandem , Falha de Tratamento , Tirosina Quinase 3 Semelhante a fms/genéticaRESUMO
BACKGROUND: Pharmacodynamic separation of pemetrexed and erlotinib avoids negative cellular interactions and results in antitumor synergy in erlotinib-resistant non-small-cell lung cancer (NSCLC) cells, independent of EGFR (epidermal growth factor receptor) genotype. PATIENTS AND METHODS: Patients with platinum-treated metastatic nonsquamous NSCLC were randomly assigned 1:2 to pemetrexed alone (500 mg/m2 provided intravenously on day 1) or pemetrexed followed by erlotinib (150 mg provided orally once daily on days 2-17) every 21 days. EGFR genotype was centrally confirmed by Sequenom multiplex oncogenotyping assay. The primary end point was progression-free survival (PFS), which would be considered promising for future study if median PFS was ≥ 4.5 months. RESULTS: Of 83 patients enrolled, 79 were randomized to either pemetrexed alone (n = 27) or in combination (n = 52). Fifty-nine (79%) of 75 eligible patients had tumors with confirmed EGFR genotype: 7 with activating mutations and 52 wild type. Median PFS was 4.7 and 2.9 months in the combination and pemetrexed-alone groups, respectively. In patients with EGFR wild-type tumors, median PFS was 5.3 and 3.5 months in the combination and pemetrexed-alone groups, respectively. Objective response rate (29% vs. 10%, P = .17), 6-month PFS (45% vs. 29%, P = .26), and 12-month PFS (23% vs. 10%, P = .28) were all higher in the combination arm. Rash (67% vs. 26%, P = .0007) and diarrhea (44% vs. 11%, P = .003) were significantly more common in the combination arm. CONCLUSION: In patients with unselected or EGFR wild-type advanced nonsquamous NSCLC, pharmacodynamic separation of pemetrexed and intercalated erlotinib had promising antitumor activity without new safety concerns. The combination merits further evaluation as maintenance or second-line therapy against new standards in patients with EGFR wild-type advanced NSCLC.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Receptores ErbB/genética , Cloridrato de Erlotinib/administração & dosagem , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação/genética , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Pemetrexede/administração & dosagem , Prognóstico , Taxa de SobrevidaRESUMO
BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer deaths in the United States. A minority of patients present with localized disease and surgical resection still offers patients the only hope for long-term survival. Locally advanced pancreatic cancer is defined as surgically unresectable, but has no evidence of distant metastases. The purpose of this study is to evaluate the efficacy and safety of cetuximab in combination with gemcitabine and 5-FU along with radiation therapy in locally advanced non-resectable, pancreatic adenocarcinoma, using progression free survival as the primary end point. METHODS: This was a prospective, single arm, open label pilot phase II study to evaluate the anti-tumor activity of gemcitabine (200 mg/m(2) per week) and cetuximab (250 mg/m(2) per week after an initial 400 mg/m(2) loading dose) with continuous infusion 5-FU (800 mg/m(2) over 96 hours) and daily concurrent external beam radiation therapy (50.4 Gy total dose) for six weeks (cycle 1) in patients with non-metastatic, locally advanced pancreatic adenocarcinoma. Following neoadjuvant treatment, subjects were re-evaluated for response and surgical candidacy with restaging scans. After resection, or also if not resected; subjects received further therapy with four 28-day cycles (cycles 2-5) of weekly gemcitabine (1000 mg/m(2)) and cetuximab (250 mg/m(2)) on days 1, 8, and 15. RESULTS: Between 2006 and 2011, twenty-six patients were screened and eleven of them were enrolled in the study. Most common reasons for screen failures were having resectable disease, metastatic disease or co-morbidity. Ten patients were able to tolerate and complete cycle 1 of chemoradiotherapy. One patient stopped the study prematurely due to grade III diarrhea. All except this one patient received planned radiation therapy. The response evaluation after cycle 1 showed one Partial Response, eight Stable Disease and two Progressive Disease. Four patients subsequently underwent surgical resection of the tumor. All patients had R0 resections. There was one preoperative mortality due to multiple organ failure. Median progression free survival (PFS) for four resected patients was 9.0 months while for unresected patients median PFS was 7.1 months. Median overall survival (OS) for four resected patients was 47.4 months and for unresected patients median OS was 17.0 months. Most common adverse events were hematologic (27%). Only two patients developed grade 3 neutropenia. Most common treatment related non-hematologic adverse events were diarrhea (10 of 11), nausea (8 of 11) and skin rash (10 of 11 patients). Only 9.5% of all reported non-hematologic adverse events were grade 3 or higher. CONCLUSIONS: The combination of cetuximab, weekly gemcitabine and continuous infusion of 5-FU with radiotherapy was quite well tolerated with intriguing clinical benefit and survival results in carefully selected patients with locally advanced pancreatic adenocarcinoma. A trial with larger sample size will be necessary to confirm these results.
RESUMO
BACKGROUND: This study aimed to establish the maximum tolerated dose (MTD) of weekly bortezomib in combination with fixed standard doses of carboplatin and bevacizumab, and to estimate the efficacy (response rate and progression free survival [PFS]) and safety of combination therapy with carboplatin, bortezomib, and bevacizumab as first-line therapy in patients with advanced non-small-cell lung cancer (NSCLC). METHODS: Patients were assigned to three dose levels of weekly bortezomib with the fixed standard doses of carboplatin AUC 6 and bevacizumab (15 mg/kg) every 3 weeks using a standard phase-I design. Bortezomib doses were 1.3 mg/m, 1.6 mg/m, and 1.8 mg/m weekly on day 1 and day 8 of every 3-week cycle. A maximum of six cycles was administered. Patients with complete, partial response or stable disease were continued on single-agent bevacizumab (15 mg/kg every 3 weeks) as maintenance therapy. In phase II, either level III or MTD was administered to evaluate the efficacy and safety of the combination in first-line treatment of advanced NSCLC. RESULTS: Sixteen patients were enrolled (three, four, and nine patients in dose level I, II, and III, respectively). There was no predefined dose limiting toxicity in cycle 1 in all 16 patients. The recommended phase-II dose is bortezomib 1.8 mg/m weekly on day 1 and day 8 in combination with carboplatin AUC 6 and bevacizumab 15 mg/kg on every 21-day cycle. Totally 9 patients were treated at the recommended phase-II dose level. The most common treatment related grade-3/4 toxicities during the subsequent cycles were thrombocytopenia (58%), lymphopenia (25%), neutropenia (12%), and diarrhea (25%). The grade-1/2 neuropathy was seen in 7 out of 16 patients (44%). The response rate, PFS, and overall survival in all patients were 37.5% (95%CI 13.8%-61.2%), 5.0 months (95%CI: 3.1-8.4), 9.9 months (95% CI: 8.2-14.1), and among the 9 patients in phase-II portion are 44% (95%CI 15.3%-77.3%), 5.5 months (95%CI: 3.1-2.2) and 10.9 months (95%CI: 8.0-14.1). CONCLUSION: The recommended phase-II dose for this combination is: carboplatin AUC 6, bevacizumab 15 mg/kg on day 1 and bortezomib 1.8 mg/m on day 1 and day 8 on every 21-day cycle. The regimen was very well tolerated with interesting clinical activity in first-line treatment of NSCLC.