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Although an association exists between the timing of immune checkpoint inhibitor (ICI) administration and therapeutic efficacy in several types of cancer, to the best of our knowledge, no reports exist regarding this relationship in gastric cancer (GC). The present study aimed to evaluate the optimal timing of ICI (nivolumab) administration in patients with advanced GC. A total of 58 consecutive patients with advanced GC who received nivolumab monotherapy after ≥2 chemotherapy regimens were retrospectively evaluated. These patients were divided into two groups according to the median time of nivolumab administration: i) Early-timing and (ii) late-timing groups, and the efficacy was assessed in both groups. The early-timing group had significantly longer overall survival (OS) than the late-timing group [median OS 8.2 months; 95% confidence interval (CI), 4.2-12.9 vs. median OS 5.4 months; 95% CI, 3.6-6.1]. Moreover, patients in the early-timing group had significantly longer progression-free survival (PFS) than those in the late-timing group (median PFS 2.6 months; 95% CI, 1.3-3.9 months vs. median PFS 1.6 months; 95% CI, 0.9-2.1 months). Furthermore, univariate analysis showed that early timing, immune-related adverse events and nonsteroidal anti-inflammatory drug administration were associated with longer OS and PFS. Cutoff Finder analysis revealed that the optimal timing of nivolumab administration for achieving better outcomes was before 12:06 p.m. Nivolumab administration in the morning, especially before 12:06 p.m., had a better clinical impact on patients with advanced GC.
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Purpose: Elastomeric infusion pumps are widely used in colorectal cancer chemotherapy. However, no studies to date have investigated patient preferences regarding different infusion pump types. Patients and Methods: Twenty patients with unresectable colorectal cancer undergoing chemotherapy were initially treated with a portable hard-shelled continuous infusion pump, followed by a soft-shelled continuous infusion pump. The respondents used a numerical rating scale (0-10) to rate their comfort when using each pump, their ease of carrying it, the pump size and shape, its weight, their ease of reading its memory, and their overall satisfaction with it. They were then asked to determine which pump they would ultimately prefer. Results: In terms of comfort, significantly higher user satisfaction was reported for the soft-shelled pump during the daytime and when going out (P < 0.001, P < 0.001, respectively). For pump portability, size, shape, and weight, the soft-shelled type also outperformed the hard-shelled one (P < 0.001, P=0.0011, P < 0.001, respectively). However, the hard-shelled pump scored significantly better in terms of ease of viewing memory (P < 0.001). Overall satisfaction was significantly higher for the soft-shelled pump than the hard-shelled type (P=0.0095). Finally, 13 patients (65%) indicated that they would prefer a soft-shelled pump for their next treatment, while only one patient (5%) preferred a hard-shelled alternative. A preference for soft-shelled pump was observed, particularly in female patients and those with a body mass index of < 22 kg/m2. Conclusion: The selection of portable elastomeric infusion pumps should consider the preferences of patients with colorectal cancer, as these devices have the potential to enhance their quality of life.
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This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab-paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment.
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Albuminas , Protocolos de Quimioterapia Combinada Antineoplásica , Desoxicitidina , Combinação de Medicamentos , Fluoruracila , Gencitabina , Irinotecano , Leucovorina , Oxaliplatina , Paclitaxel , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Masculino , Feminino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucovorina/uso terapêutico , Leucovorina/administração & dosagem , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Paclitaxel/uso terapêutico , Idoso , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Albuminas/administração & dosagem , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/uso terapêutico , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Ácido Oxônico/administração & dosagem , Ácido Oxônico/uso terapêutico , Tegafur/administração & dosagem , Tegafur/uso terapêutico , Adulto , Lipossomos , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
Nanoliposomal irinotecan with fluorouracil and folinic acid (NFF) is a standard regimen after gemcitabine-based therapy for patients with unresectable or recurrent pancreatic cancer. However, there are limited clinical data on its efficacy and safety in the real-world. We therefore initiated a retrospective and prospective observational study (NAPOLEON-2). The results of the retrospective part were reported herein. In this retrospective study, we evaluated 161 consecutive patients who received NFF as second-or-later-line regimen. The main endpoint was overall survival (OS), and the other endpoints were response rate, disease control rate, progression-free survival (PFS), dose intensity, and adverse events (AEs). The median age was 67 years (range, 38-85 years). The median OS and PFS were 8.1 and 3.4 months, respectively. The objective response and disease control rates were 5% and 52%, respectively. The median relative dose intensity was 81.6% for nanoliposomal irinotecan and 82.9% for fluorouracil. Grade 3 or 4 hematological and nonhematological AEs occurred in 47 and 42 patients, respectively. Common grade 3 or 4 AEs included neutropenia (24%), anorexia (12%), and leukocytopenia (12%). Subanalysis of patients treated with second-line and third-or-later-line demonstrated no statistical significant difference in OS (7.6 months vs. 9.1 months, respectively; hazard ratio, 0.92; 95% confidence interval, 0.64-1.35; p = 0.68). In conclusion, NFF has acceptable efficacy and safety profile even in real-world clinical settings. The prospective study is in progress to validate these findings.
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Protocolos de Quimioterapia Combinada Antineoplásica , Fluoruracila , Irinotecano , Leucovorina , Lipossomos , Neoplasias Pancreáticas , Humanos , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Idoso , Leucovorina/administração & dosagem , Leucovorina/uso terapêutico , Leucovorina/efeitos adversos , Irinotecano/administração & dosagem , Irinotecano/uso terapêutico , Irinotecano/efeitos adversos , Feminino , Pessoa de Meia-Idade , Masculino , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Resultado do Tratamento , Estudos ProspectivosRESUMO
Certain genetic alterations and right-sided primary tumor location are associated with resistance to anti-epidermal growth factor (EGFR) treatment in metastatic colorectal cancer (mCRC). The phase 3 PARADIGM trial (n = 802) demonstrated longer overall survival with first-line anti-EGFR (panitumumab) versus antivascular endothelial growth factor (bevacizumab) plus modified FOLFOX6 in patients with RAS wild-type mCRC with left-sided primary tumors. This prespecified exploratory biomarker analysis of PARADIGM (n = 733) evaluated the association between circulating tumor DNA (ctDNA) gene alterations and efficacy outcomes, focusing on a broad panel of gene alterations associated with resistance to EGFR inhibition, including KRAS, NRAS, PTEN and extracellular domain EGFR mutations, HER2 and MET amplifications, and ALK, RET and NTRK1 fusions. Overall survival was prolonged with panitumumab plus modified FOLFOX6 versus bevacizumab plus modified FOLFOX6 in patients with ctDNA that lacked gene alterations in the panel (that is, negative hyperselected; median in the overall population: 40.7 versus 34.4 months; hazard ratio, 0.76; 95% confidence interval, 0.62-0.92) but was similar or inferior with panitumumab in patients with ctDNA that contained any gene alteration in the panel (19.2 versus 22.2 months; hazard ratio, 1.13; 95% confidence interval, 0.83-1.53), regardless of tumor sidedness. Negative hyperselection using ctDNA may guide optimal treatment selection in patients with mCRC. ClinicalTrials.gov registrations: NCT02394834 and NCT02394795 .
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Humanos , Panitumumabe/uso terapêutico , Bevacizumab/uso terapêutico , Anticorpos Monoclonais/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias do Colo/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Biomarcadores , Receptores ErbB/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)RESUMO
First-line chemotherapy for patients with metastatic pancreatic cancer (MPC) includes gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX (FFX). However, the efficacy of second-line chemotherapy and the role of combination chemotherapy in clinical practice is still unknown. Data was gathered from 14 hospitals in the Kyushu area of Japan from December 2013 to March 2017. The median overall survival (mOS) from second-line treatment was contrasted between patients who received second-line chemotherapy (CT group) and those who received the best supportive care (BSC group). Furthermore, the mOS of combination chemotherapy was compared to mono chemotherapy in the CT group. To control possible bias in the selection of treatment, we performed a propensity score-adjusted analysis. A total of 255 patients received GnP or FFX as first-line chemotherapy. There were 156 in the CT group and 77 in the BSC group of these. The CT group had a significantly longer mOS than the BSC group (5.2 vs. 2.6 months; adjusted hazard ratio (HR) 0.38; 95% CI 0.27-0.54). In the CT group, 89 patients received combination chemotherapy while 67 received mono chemotherapy. The mOS did not differ significantly between the combination and mono chemotherapy groups (5.5 vs. 4.8 months; adjusted HR 0.88; 95% CI 0.58-1.33). Among patients with MPC receiving second-line treatment, the CT group had a significantly longer mOS than the BSC group, but combination chemotherapy conferred no improvement in survival compared to mono chemotherapy.
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Pancreáticas , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gencitabina , Neoplasias Pancreáticas/tratamento farmacológicoRESUMO
Introduction: Expression of the NTRK gene is rare in solid tumors but is highly prevalent in salivary gland secretory carcinomas. Here, we report a case of a complete response to entrectinib in a patient with NTRK fusion gene-positive parotid carcinoma. Case description: The patient was a 44-year-old man who underwent total left parotidectomy and left cervical lymph node dissection for a left parotid tumor at 24 years of age. The histopathological diagnosis was mammary analog secretory carcinoma. Postoperatively, the patient received only radiation therapy. Sixteen years after the surgery, the patient became aware of a mass in the left parotid region. A close examination revealed local recurrence and multiple cervical lymph node metastases. S-1 monotherapy was started as chemotherapy but was discontinued 3 years later because of disease progression. As there was no standard treatment, a comprehensive genomic profiling test using a next-generation sequencer was performed, and the ETV6-NTRK3 fusion gene was identified. Entrectinib, an NTRK inhibitor, was immediately administered at a dose of 600 mg/day. The local recurrence rapidly shrank grossly from the beginning of treatment, and a complete response was observed 6 months later. However, creatinine levels exhibited an increase at week 68 of treatment; consequently, entrectinib dosage was lowered to 400 mg/day, leading to an immediate improvement in creatinine levels. Entrectinib was associated with additional side effects, including dysgeusia, fatigue, dizziness, and weight gain, all of which were also alleviated by the reduction in entrectinib dose. Thirty months after treatment initiation, the patient maintained a complete response and continued to receive entrectinib. Conclusion: The NTRK fusion gene should always be checked in the presence of salivary gland secretory carcinoma.
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BACKGROUND/AIM: The aim of this study was to evaluate hepatectomy cases that underwent preoperative chemotherapy to examine the relationship between the development of desmoplastic histopathological growth pattern (dHGP) and prognosis and recurrence and determine whether it is useful for evaluating preoperative chemotherapy. PATIENTS AND METHODS: A total of 133 cases with hepatic metastasis for colorectal cancer that underwent surgical resection. RESULTS: Of the 102 cases that underwent preoperative chemotherapy, 34 (33%) were determined to be dHGP positive, which was statistically significantly higher than the 2 of 31 cases (6.5%) that had not undergone preoperative chemotherapy. Regarding the 5-year recurrence-free survival, the dHGP group had a value of 50.3%, whereas the non-dHGP group had a value of 7.1%. For the 5-year overall survival, the dHGP group had a better prognosis than the non-dHGP group (57.6% vs. 37.1%, respectively), with a statistically significant difference. Univariate analysis of recurrence-free survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and the presence or absence of dHGP were prognostic factors, whereas multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. Univariate analysis of the overall survival showed that the number of tumours, the Response Evaluation Criteria in Solid Tumors, and presence or absence of dHGP were prognostic factors. Multivariate analysis showed that the presence or absence of dHGP was an independent prognostic factor. CONCLUSION: dHGP is useful as a new evaluation method for evaluating the efficacy of preoperative chemotherapy.
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Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/cirurgia , Neoplasias Colorretais/patologia , Prognóstico , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/patologia , Hepatectomia , Quimioterapia Adjuvante , Estudos RetrospectivosRESUMO
BACKGROUND/AIM: Hepatic recurrences after resection of metastatic lesions in advanced colorectal cancer (CRC) have an enormous impact on patient prognosis. Response evaluation criteria in solid tumor (RECIST) or morphologic response on computed tomography (CT) have been reported as surrogate prognostication markers. This study assessed a novel algorithm for the prognostication of liver metastasis treatment. PATIENTS AND METHODS: Forty-seven patients with liver metastases from CRC who underwent liver resection after systemic chemotherapy were included. The CT values examined before and after chemotherapy were collected. The velocity of CT values (CTvΔ) was calculated, and the subjects were divided into CTvΔ_high and _low groups. Clinicopathological variables, recurrence-free survival (RFS), and overall survival (OS) were statistically compared between the two groups. In addition, the effect of the combined evaluation of CTvΔ and carcinoembryonic antigen (CEA) was evaluated. RESULTS: In univariate analyses, the hazard ratio (HR) for a recurrence after liver resection was relatively higher in the RECIST_stable disease (SD) or _progressive disease (PD) and the CTvΔ_low groups. In multivariate analysis, the HR was significantly higher in the CEA_high, the RECIST_SD or PD, and the CTvΔ_low groups. The RFS was significantly longer in the CTvΔ_high group. Furthermore, the combination of CTvΔ and CEA predicted the RFS and OS. CONCLUSION: Our algorithm using CTvΔ could be a useful tool to select patients suitable for liver resection of hepatic CRC metastases.
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Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Hepáticas , Neoplasias Retais , Humanos , Antígeno Carcinoembrionário , Neoplasias Colorretais/patologia , Prognóstico , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/tratamento farmacológico , Recidiva , Estudos RetrospectivosRESUMO
Introduction: Reports on the long-term quality of life (QOL) over 3 years after surgery in patients who have undergone surgery for rectal cancer are limited. Therefore, we aimed to evaluate the long-term QOL of patients who underwent high anterior resection (HAR), low anterior resection (LAR), internal sphincter resection (ISR), or abdominoperineal resection (APR) for rectal cancer. Methods: A questionnaire regarding QOL was sent to 360 patients with rectal cancer who underwent curative resection by HAR, LAR, ISR, or APR between January 2005 and December 2015. QOL was assessed using the short-form 36 (SF-36) and modified fecal incontinence QOL (mFIQL) questionnaire. QOL between surgical procedures was analyzed using a multivariate model adjusted for age, sex, and postoperative time. Results: A total of 144 patients responded with a median follow-up period of 94 months (range 38-233 months). According to surgical procedure, HAR was performed in 26 patients, LAR in 80 patients, ISR in 32 patients, and APR in 6 patients. Patients who underwent HAR had significantly better mFIQL scores than those who underwent LAR and ISR (p=0.013 and p=0004, respectively) and significantly better role/social component summary scores on the SF-36 subscales (p=0.007). No difference was observed in the mFIQL scores between patients who underwent ISR and those who underwent APR (p=0.8423). In addition, postoperative anastomotic leakage sutures did not influence the mFIQL and SF-36 scores after surgery. Conclusion: The QOL of patients who underwent anus-preserving surgery was best in the HAR group, with the QOL of other groups similar to the APR group. These results suggest that anus- preserving surgery is acceptable from a QOL standpoint. However, a colostomy may be a more satisfactory procedure in some patients.
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BACKGROUND: Nivolumab extends the overall survival (OS) of patients with advanced gastric cancer (AGC). Intramuscular adipose tissue (IMAT) is associated with the prognosis of patients with various cancers. We investigated the effect of IMAT on OS in patients with AGC treated with nivolumab. METHODS: We enrolled patients with AGC treated with nivolumab (n = 58, 67 years old, men/women 40/18). The subjects were classified into long-term or short-term survival groups according to the median value. The IMAT was evaluated using computed tomography scans at the umbilical level. The decision tree algorithm was employed to reveal the profile associated with prognosis. RESULTS: In decision tree analysis, immune-related adverse events (irAEs) were the first divergence variable, and prolonged survival was observed in 100% of patients with irAEs (profile 1). However, long survival was observed in 38% of patients with no irAEs. Among these patients, IMAT was identified as the second divergence variable, and long survival was observed in 63% of patients with high IMAT (profile 2). In patients with low IMAT, only 21% showed prolonged survival (profile 3). Median OS was 717 days (95% confidence interval [CI], 223 to not reached) in profile 1, 245 days (95% CI, 126 to 252) in profile 2, and 132 days (95% CI, 69 to 163) in profile 3. CONCLUSION: Immune-related adverse events and high IMAT were favorable factors for OS in patients with AGC treated with nivolumab. Thus, along with irAEs, skeletal muscle quality is important in managing patients with AGC treated with nivolumab.
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Nivolumabe , Neoplasias Gástricas , Masculino , Humanos , Feminino , Idoso , Nivolumabe/efeitos adversos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/induzido quimicamente , Prognóstico , Estudos Retrospectivos , Tecido Adiposo/diagnóstico por imagemRESUMO
Bevacizumab (BEV) requires an adequate withdrawal period to avoid BEV-related complications during major surgery. However, the safety of BEV administration immediately after surgical placement of the central venous (CV) port, a minor surgery, is still unclear. This study aimed to investigate whether BEV is safe when administered early after CV port placement. We retrospectively evaluated 184 patients with advanced colorectal cancer (CRC) treated with a BEV-containing regimen and divided them into two groups according to the interval between CV port implantation and chemotherapy initiation, with the early administration group being ≤7 days and late administration group being >7 days. Complications were then compared between the two groups. The early-administration group was significantly older and had a higher rate of colon cancer than the late-administration group. Overall, 24 (13%) patients developed CV port-related complications. Male sex was a risk factor for complications (odds ratio [OR], 3.154; 95% CI, 1.19-8.36). The two groups showed no significant difference in the frequency of complications (p = 0.84) or patient characteristics (after the inverse probability of treatment weighting, p = 0.537). In conclusion, the frequency of complications is not affected by the timing of BEV initiation after CV port implantation. Thus, early BEV administration after CV port placement is safe.
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Importance: For patients with RAS wild-type metastatic colorectal cancer, adding anti-epidermal growth factor receptor (anti-EGFR) or anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies to first-line doublet chemotherapy is routine, but the optimal targeted therapy has not been defined. Objective: To evaluate the effect of adding panitumumab (an anti-EGFR monoclonal antibody) vs bevacizumab (an anti-VEGF monoclonal antibody) to standard first-line chemotherapy for treatment of RAS wild-type, left-sided, metastatic colorectal cancer. Design, Setting, and Participants: Randomized, open-label, phase 3 clinical trial at 197 sites in Japan in May 2015-January 2022 among 823 patients with chemotherapy-naive RAS wild-type, unresectable metastatic colorectal cancer (final follow-up, January 14, 2022). Interventions: Panitumumab (n = 411) or bevacizumab (n = 412) plus modified fluorouracil, l-leucovorin, and oxaliplatin (mFOLFOX6) every 14 days. Main Outcomes and Measures: The primary end point, overall survival, was tested first in participants with left-sided tumors, then in the overall population. Secondary end points were progression-free survival, response rate, duration of response, and curative (defined as R0 status) resection rate. Results: In the as-treated population (n = 802; median age, 66 years; 282 [35.2%] women), 604 (75.3%) had left-sided tumors. Median follow-up was 61 months. Median overall survival was 37.9 months with panitumumab vs 34.3 months with bevacizumab in participants with left-sided tumors (hazard ratio [HR] for death, 0.82; 95.798% CI, 0.68-0.99; P = .03) and 36.2 vs 31.3 months, respectively, in the overall population (HR, 0.84; 95% CI, 0.72-0.98; P = .03). Median progression-free survival for panitumumab vs bevacizumab was 13.1 vs 11.9 months, respectively, for those with left-sided tumors (HR, 1.00; 95% CI, 0.83-1.20) and 12.2 vs 11.4 months overall (HR, 1.05; 95% CI, 0.90-1.24). Response rates with panitumumab vs bevacizumab were 80.2% vs 68.6%, respectively, for left-sided tumors (difference, 11.2%; 95% CI, 4.4%-17.9%) and 74.9% vs 67.3% overall (difference, 7.7%; 95% CI, 1.5%-13.8%). Median duration of response with panitumumab vs bevacizumab was 13.1 vs 11.2 months for left-sided tumors (HR, 0.86; 95% CI, 0.70-1.10) and 11.9 vs 10.7 months overall (HR, 0.89; 95% CI, 0.74-1.06). Curative resection rates with panitumumab vs bevacizumab were 18.3% vs 11.6% for left-sided tumors; (difference, 6.6%; 95% CI, 1.0%-12.3%) and 16.5% vs 10.9% overall (difference, 5.6%; 95% CI, 1.0%-10.3%). Common treatment-emergent adverse events were acneiform rash (panitumumab: 74.8%; bevacizumab: 3.2%), peripheral sensory neuropathy (panitumumab: 70.8%; bevacizumab: 73.7%), and stomatitis (panitumumab: 61.6%; bevacizumab: 40.5%). Conclusions and Relevance: Among patients with RAS wild-type metastatic colorectal cancer, adding panitumumab, compared with bevacizumab, to standard first-line chemotherapy significantly improved overall survival in those with left-sided tumors and in the overall population. Trial Registration: ClinicalTrials.gov Identifier: NCT02394795.
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Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Neoplasias Colorretais , Panitumumabe , Idoso , Feminino , Humanos , Masculino , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab/administração & dosagem , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila/administração & dosagem , Leucovorina/administração & dosagem , Panitumumabe/administração & dosagem , Panitumumabe/efeitos adversos , Panitumumabe/uso terapêutico , Oxaliplatina/administração & dosagem , Receptores ErbB/antagonistas & inibidores , Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidoresRESUMO
The occurrence of fulminant type 1 diabetes mellitus as an adverse event during cancer immunotherapy has been previously reported. However, little is known about the causal relationship between the coronavirus disease 2019 (COVID-19) vaccination and fulminant type 1 diabetes mellitus. A 60-year-old man with advanced gastric cancer, receiving S-1 + oxaliplatin and nivolumab therapy, followed by nab-paclitaxel + ramucirumab as a second-line treatment, with steroid supplementation for complications of hypopituitarism-induced hypoadrenocorticism, was administered a COVID-19 vaccine after three cycles of nab-paclitaxel + ramucirumab. Two days later, he developed severe malaise and anorexia, which required emergency admission to our hospital for suspected adrenal insufficiency. Despite increasing steroids, his general condition changed suddenly after 12 hours leading to his death. Histopathological analysis of autopsy samples revealed loss of the islets of Langerhans, indicating fulminant type 1 diabetes mellitus. We failed to recognize the onset of fulminant type 1 diabetes mellitus because its symptoms were similar to those of adrenal insufficiency. The number of reports on the onset of fulminant type 1 diabetes mellitus after COVID-19 vaccination has been increasing, and in this case, the onset occurred on the second day after COVID-19 vaccination, suggesting an association between vaccination and fulminant type 1 diabetes mellitus. Clinicians should be aware of the risk of fulminant type 1 diabetes mellitus, although rare, after COVID-19 vaccination.
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The global incidence of colorectal cancer (CRC) in patients receiving hemodialysis is steadily rising. However, current information on the clinical use of chemotherapy for patients undergoing hemodialysis with CRC is limited. Herein, we describe a clinical course of a 74-year-old patient undergoing hemodialysis with unresectable CRC treated with folinic acid, 5-fluorouracil (5FU), and irinotecan (FOLFIRI) plus bevacizumab whose changes in serum bevacizumab concentration were analyzed. Treatment was initiated with a standard dosage of 5-FU and 80% of the standard dose of irinotecan to avoid any adverse events. However, neutropenia (grade 4) was observed after five treatment cycles, which prompted a dose reduction of 5-FU and irinotecan, after which treatment was safely completed. Progression-free survival of the patient was 7.5 months. Changes in serum bevacizumab concentration were similar to those documented in patients with normal renal function. In addition, no bevacizumab-related adverse events occurred. It was inferred that FOLFIRI plus bevacizumab therapy could be implemented as a safe and efficient treatment for patients undergoing hemodialysis with unresectable CRC. To the best of our knowledge, this is the first report of the analysis of serum bevacizumab concentrations in a patient undergoing hemodialysis with unresectable CRC.
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Trousseau syndrome-related cerebral infarction rarely occurs during chemotherapy in patients with gastrointestinal (GI) cancer, and its clinical features remain unclear. The present study aimed to examine the clinical features of Trousseau syndrome-related cerebral infarction developed during chemotherapy for GI cancer. The present retrospective cohort study consecutively enrolled 878 patients with unresectable GI cancer who received chemotherapy at the Multidisciplinary Treatment Cancer Center, Kurume University Hospital (Kurume, Japan) between April 2014 and March 2020. Patients with colorectal cancer (n=308) were the most common, followed by those with pancreatic (n=242), gastric (n=222) and biliary tract (n=59) cancer, neuroendocrine tumors (n=34) and duodenal cancer (n=11). Among the 878 patients, Trousseau syndrome-related cerebral infarction occurred in 8 (0.9%) patients with a median age of 70.5 years (range, 58-75 years), and 50% of the patients were male (4/8). In total, 3 patients had gastric cancer, 3 had pancreatic cancer and 2 had biliary tract cancer. A greater percentage of patients with Trousseau syndrome-related cerebral infarction had hyperlipidemia (38.0%) than those without (8.2%; P=0.005). Hyperlipidemia was a risk factor for occurrence of Trousseau syndrome-related cerebral infarction with an odds ratio of 7.009 (95% confidence interval, 1.785-27.513). Trousseau syndrome-related cerebral infarction developed during GI chemotherapy was rare and hyperlipidemia may predict its onset.
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ABSTRACT: Gemcitabine plus nab-paclitaxel (GnP) is widely used in clinical practice, despite a lack of prospective data to validate its efficacy in locally advanced pancreatic cancer (LAPC). We conducted a phase II study of GnP for LAPC to assess its efficacy and safety.We performed a single-arm, single-institution study with GnP in 24 patients with LAPC. The treatment protocol included successive administration of gemcitabine (1000âmg/m2) and nab-paclitaxel (125âmg/m2). The primary endpoint was the tumor overall response rate (ORR), and secondary endpoints were overall survival (OS), progression-free survival (PFS), and adverse events (AEs).The median PFS was 11.0 months, median OS was 21.2 months, ORR was 62.5%, and 37.5% of the patients had stable disease. Four (16.7%) of the patients were converted to surgical resection; 3 of these achieved R0 resection. Grade 3 to 4 AEs included hematological (neutropenia, 64%; thrombocytopenia, 12%), nonhematological (cholangitis, 16%), and sensory neuropathy (4%). These AEs were manageable and tolerable.The GnP treatment in patients with LAPC showed favorable tumor shrinkage, good toxicity profile, and enabled conversion to surgical resection in a subset of patients; therefore, GnP is an option for first-line chemotherapy in patients with LAPC.
Assuntos
Albuminas/uso terapêutico , Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Ductal Pancreático/tratamento farmacológico , Desoxicitidina/análogos & derivados , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Desoxicitidina/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Intervalo Livre de Progressão , Estudos Prospectivos , Taxa de Sobrevida , Resultado do Tratamento , GencitabinaRESUMO
BACKGROUND: Apart from Kasai's procedure, liver transplantation (LTx) has dramatically improved the outcome of children with biliary atresia (BA). However, de novo malignancy has been reported to be one of the major causes of late mortality after LTx among adults. We report a rare case of de novo gastric cancer developing after LTx for BA received during childhood. CASE PRESENTATION: A 21-year-old male patient who had undergone LTx for BA at age 2 years occasionally visited our outpatient clinic due to symptoms of epigastric pain and dysphagia. Endoscopic examination and computed tomography revealed advanced gastric cancer at the gastroesophageal junction with multiple liver metastases. Despite systemic chemotherapy, the disease progressed, resulting in patient's death 2 years after the diagnosis. CONCLUSIONS: De novo malignancy in the absence of post-transplant lymphoproliferative disease is rare in pediatric patients who received LTx. To the best of our knowledge, no report has been available on the development of gastric cancer after LTx for BA during childhood. Primary physicians should therefore establish a follow-up plan for patients receiving LTx for BA considering the potential for the development of de novo malignancy, including gastric cancer, despite its rarity.
RESUMO
BACKGROUND: The efficacy of balloon pulmonary angioplasty (BPA) in patients with inoperable chronic thromboembolic pulmonary hypertension would be promising. However, some patients showed residual dyspnea or symptoms, despite normalized hemodynamics. We aimed to clarify the clinical impact of oxygenation parameters on BPA outcome. METHOD: Ninety-nine consecutive patients who underwent BPA from September 2011 to December 2019 were enrolled. We evaluated hemodynamics with right heart catheterization, arterial blood gas examination, New York Heart Association functional class (NYHA-FC), respiratory function tests, nocturnal oximetry, and exercise capacity (6-min walk test and cardiopulmonary exercise testing) at baseline and after BPA. RESULT: Nearly normal hemodynamics was achieved after BPA (mean pulmonary artery pressure (PAP): 37.5 ± 10.0 to 20.6 ± 4.9 mmHg, p < 0.01). Oxygenation slightly improved (partial pressure of arterial oxygen; 61.5 ± 12.3 to 67.7 ± 12.7 mmHg, p < 0.01). Exertional desaturation remained unchanged (-8.1 ± 4.8 to -7.8 ± 5.1, p = 0.59), and this was associated with residual symptom (NYHA-FC ≥ 2) after BPA (OR 0.591, 95% CI 0.416-0.840, p = 0.003) in multivariate regression analyses. Lower vital capacity (r2 = 0.03, p = 0.01), higher mean PAP (r2 = 0.08, p = 0.02), and higher minute ventilation/carbon dioxide production (VE/VCO2) slope (r2 = 0.18, p < 0.01), the marker of ventilatory inefficiency, were correlated with exertional desaturation after BPA in multivariate linear analyses. CONCLUSION: Although hemodynamics nearly normalized, oxygenation did not. Moreover, exertional desaturation remained unchanged. This might cause residual symptom after BPA. Residual pulmonary hypertension suggesting incurable arteriopathy, and higher VE/VCO2 slope suggesting ventilation-perfusion mismatch might be related to exertional desaturation. Domiciliary oxygen therapy should be continued, if necessary.