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1.
Medicine (Baltimore) ; 100(21): e26143, 2021 May 28.
Article in English | MEDLINE | ID: covidwho-2191018

ABSTRACT

INTRODUCTION: Coronavirus disease 2019 (COVID-19) is a rapidly emerging infectious respiratory disease caused by severe acute respiratory syndrome coronavirus 2. Currently, more than 100 million cases of COVID-19 have been confirmed worldwide, with over 2.4 million mortalities. The pandemic affects people of all ages but older individuals and those with severe chronic illnesses, including cancer patients, are at higher risk. PATIENT CONCERNS: The impact of cancer treatment on the progression of COVID-19 is unclear. Therefore, we assessed the effects of chemotherapy on COVID-19 outcomes for 2 cancer patients. On January 24, 2020, a level I response to a major public health emergency was initiated in Hubei Province, China, which includes Enshi Autonomous Prefecture that has a population of 4.026 million people. As of April 30, 2020, 252 confirmed cases of COVID-19 and 11 asymptomatic carriers were identified in Enshi. DIAGNOSIS: Among the confirmed cases and asymptomatic carriers, 2 patients were identified who were previously diagnosed with malignant tumors, including one with hepatocellular carcinoma and the other with cardia carcinoma. INTERVENTIONS: These 2 patients were receiving or just completed chemotherapy at the time of their COVID-19 diagnosis. OUTCOMES: Both patients were followed and presented favorable outcomes. The positive outcomes for these 2 patients could be partially explained by their recent chemotherapy that impacted their immune status. Also, their relatively younger ages and lack of comorbidities were likely factors in their successful recovery from COVID-19. CONCLUSIONS: Anticancer treatment might enhance a patient's ability to respond favorably to COVID-19 infection. However, anticancer treatment is likely to impact immune function differently in different individuals, which can influence disease outcomes.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/immunology , Liver Neoplasms/drug therapy , SARS-CoV-2/immunology , Stomach Neoplasms/drug therapy , Adult , COVID-19/complications , COVID-19/diagnosis , COVID-19/drug therapy , COVID-19 Nucleic Acid Testing , Cyclobutanes/therapeutic use , Docetaxel/therapeutic use , Drug Therapy, Combination/methods , Humans , Liver Neoplasms/complications , Liver Neoplasms/immunology , Lung/diagnostic imaging , Male , Middle Aged , Organoplatinum Compounds/therapeutic use , RNA, Viral/isolation & purification , SARS-CoV-2/genetics , SARS-CoV-2/isolation & purification , Sorafenib/therapeutic use , Stomach Neoplasms/complications , Stomach Neoplasms/immunology , Tomography, X-Ray Computed , Treatment Outcome
2.
Oncol Res Treat ; 45(11): 681-692, 2022.
Article in English | MEDLINE | ID: covidwho-2162084

ABSTRACT

BACKGROUND: Metronomic chemotherapy (MCT), termed sustained low-dose administration with minimal toxicity, is a new modality of conventional chemotherapy, a verified therapy alternative, and has acquired significant recognition and interest in oncology. Numerous clinical trials of MCT in combination with other treatments, including targeted therapies, biologics, and endocrine therapy, are in progress to obtain better results. SUMMARY: We comprehensively described the clinical benefits of MCT in combination with other treatments in different molecular subtypes of breast cancer and assessed the feasibility of its adoption in varying phases of treatment. Due to the promising preclinical and clinical investigations, it is expected that MCT in combination with other treatments will enhance the advantages of this strategy and apply it to clinical practice. KEY MESSAGE: MCT, in combination with other therapeutic interventions, will fully exploit the benefits of this strategy, ushering in a new paradigm in oncology treatment and driving the transformation of cancer into a more manageable chronic disease using newly developed treatment approaches.


Subject(s)
Breast Neoplasms , Humans , Female , Breast Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
3.
Am J Case Rep ; 23: e937500, 2022 Sep 24.
Article in English | MEDLINE | ID: covidwho-2121397

ABSTRACT

BACKGROUND Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL). While bone marrow (BM) involvement is common in lymphoma, primary bone marrow (PBM) DLBCL is extremely rare. We present a case of PBM DLBCL discovered in a patient with COVID-19. CASE REPORT An 80-year-old man presented with generalized abdominal pain, weight loss, fever, fatigue, anorexia, and watery diarrhea over a 3-month period. Physical examination was unremarkable. Laboratory workup revealed anemia, thrombocytopenia, and elevated inflammation markers. SARS-COV-2 PCR was positive, while blood cultures were negative. A rapid decline in the white blood cell count in the following days prompted a BM biopsy, confirming the diagnosis of PBM DLBCL. Computed tomography (CT) did not show thoracic or abdominal lymphadenopathy. The patient received packed red blood cell and platelet transfusions, granulocyte colony-stimulating factor (G-CSF) for pancytopenia, and empirical antibiotics for suspected infection. Due to active COVID-19 and advanced age, cytotoxic chemotherapy was delayed. Rituximab and prednisone were initiated on day 9, followed by an infusion reaction, which led to treatment discontinuation. He died 2 days later. CONCLUSIONS Diagnosing PBM malignancy is challenging, especially with coexisting infection. It is essential to suspect underlying BM malignancy in patients with clinical deterioration and worsening pancytopenia despite adequate treatment. The diagnosis of PBM DLBCL requires the absence of lymphadenopathy, and the presence of histologically confirmed DLBCL. Prompt management with combination chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with/without hematopoietic stem cell transplant can improve the prognosis.


Subject(s)
COVID-19 , Lymphadenopathy , Lymphoma, Large B-Cell, Diffuse , Pancytopenia , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bone Marrow/pathology , COVID-19/complications , Cyclophosphamide/therapeutic use , Doxorubicin/therapeutic use , Granulocyte Colony-Stimulating Factor/therapeutic use , Humans , Lymphadenopathy/pathology , Lymphoma, Large B-Cell, Diffuse/complications , Lymphoma, Large B-Cell, Diffuse/diagnosis , Lymphoma, Large B-Cell, Diffuse/therapy , Male , Pancytopenia/etiology , Prednisone/therapeutic use , Rituximab/therapeutic use , SARS-CoV-2 , Vincristine/therapeutic use
4.
Ter Arkh ; 94(7): 827-835, 2022 Aug 12.
Article in Russian | MEDLINE | ID: covidwho-2044341

ABSTRACT

AIM: The primary objective of the interim analysis of the MULTISPECT study was to evaluate the short-term efficacy of the treatment and long-term outcomes in cohorts of primary and pretreated patients with multiple myeloma (MM) receiving treatment in actual clinical practice in various regions of the Russian Federation. Secondary objectives were a description of the main characteristics of patients; analysis of the most commonly used therapy regimens of the 1st and later lines and the sequence of their changes; evaluation of the response to therapy. Additional objectives included evaluation of the effect of the new COVID-19 coronavirus infection on the course of MM in patients. MATERIALS AND METHODS: The study is an observational retrospective-prospective multicenter cohort study. For its implementation, a structured database of patients with MM was used, provided by hematologists of the centers affiliated for the study. RESULTS: The study included 1,294 patients (cohort 1 806, cohort 2 488). In both cohorts, patients aged 6069 years were in the majority. 3 lines of therapy (L1, L2, L3) were used for cohort 1; in cohort 2, the 4th line of therapy was also used in 2 patients. The therapy regimens were analyzed for 290 (22.41%) of all patients in the study. Responses to therapy were analyzed for 214 patients of cohort 1 and 109 patients of cohort 2. Autologous and allogeneic hematopoietic stem cell transplantations were carried out for a limited proportion of patients in both cohorts. At the end of the study and upon presentation of its results, the status of patients was the following: 96% of patients in cohort 1 and 89% in cohort 2 were alive. The therapy regimens in both cohorts were characterized by variability. The most commonly used regimens in each of the lines of therapy have been identified. The most used therapy regimen in patients with MM of both cohorts was the VCD-regime. Rd-regime in cohort 1 and RD-regime in cohort 2 were the second most frequent used regimens. In patients of both cohorts, the therapy regimens including Bortezomib were most often used. CONCLUSION: The variety of therapy regimens used to treat MM in actual clinical practice may be due to the factors of availability of new medicines and updated recommendations for the treatment of the disease. Further, in the context of this study, a more detailed analysis of the efficacy of certain therapy regimens in the 1st and later lines on progression free survival and overall survival of MM patients should be carried out.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Humans , Multiple Myeloma/diagnosis , Multiple Myeloma/epidemiology , Multiple Myeloma/therapy , Bortezomib/therapeutic use , Retrospective Studies , Cohort Studies , Prospective Studies , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/therapy , Transplantation, Autologous/methods , Hematopoietic Stem Cell Transplantation/methods , Treatment Outcome , Disease-Free Survival
5.
N Engl J Med ; 387(6): 495-505, 2022 08 11.
Article in English | MEDLINE | ID: covidwho-2031919

ABSTRACT

BACKGROUND: Teclistamab is a T-cell-redirecting bispecific antibody that targets both CD3 expressed on the surface of T cells and B-cell maturation antigen expressed on the surface of myeloma cells. In the phase 1 dose-defining portion of the study, teclistamab showed promising efficacy in patients with relapsed or refractory multiple myeloma. METHODS: In this phase 1-2 study, we enrolled patients who had relapsed or refractory myeloma after at least three therapy lines, including triple-class exposure to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. Patients received a weekly subcutaneous injection of teclistamab (at a dose of 1.5 mg per kilogram of body weight) after receiving step-up doses of 0.06 mg and 0.3 mg per kilogram. The primary end point was the overall response (partial response or better). RESULTS: Among 165 patients who received teclistamab, 77.6% had triple-class refractory disease (median, five previous therapy lines). With a median follow-up of 14.1 months, the overall response rate was 63.0%, with 65 patients (39.4%) having a complete response or better. A total of 44 patients (26.7%) were found to have no minimal residual disease (MRD); the MRD-negativity rate among the patients with a complete response or better was 46%. The median duration of response was 18.4 months (95% confidence interval [CI], 14.9 to not estimable). The median duration of progression-free survival was 11.3 months (95% CI, 8.8 to 17.1). Common adverse events included cytokine release syndrome (in 72.1% of the patients; grade 3, 0.6%; no grade 4), neutropenia (in 70.9%; grade 3 or 4, 64.2%), anemia (in 52.1%; grade 3 or 4, 37.0%), and thrombocytopenia (in 40.0%; grade 3 or 4, 21.2%). Infections were frequent (in 76.4%; grade 3 or 4, 44.8%). Neurotoxic events occurred in 24 patients (14.5%), including immune effector cell-associated neurotoxicity syndrome in 5 patients (3.0%; all grade 1 or 2). CONCLUSIONS: Teclistamab resulted in a high rate of deep and durable response in patients with triple-class-exposed relapsed or refractory multiple myeloma. Cytopenias and infections were common; toxic effects that were consistent with T-cell redirection were mostly grade 1 or 2. (Funded by Janssen Research and Development; MajesTEC-1 ClinicalTrials.gov numbers, NCT03145181 and NCT04557098.).


Subject(s)
Antibodies, Bispecific , Antineoplastic Agents, Immunological , B-Cell Maturation Antigen , CD3 Complex , Multiple Myeloma , Antibodies, Bispecific/administration & dosage , Antibodies, Bispecific/adverse effects , Antibodies, Bispecific/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Antineoplastic Agents, Immunological/administration & dosage , Antineoplastic Agents, Immunological/adverse effects , Antineoplastic Agents, Immunological/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , B-Cell Maturation Antigen/antagonists & inhibitors , CD3 Complex/antagonists & inhibitors , Humans , Injections, Subcutaneous , Multiple Myeloma/drug therapy , Multiple Myeloma/immunology , Multiple Myeloma/pathology , Neoplasm Recurrence, Local/drug therapy , Recurrence , T-Lymphocytes/drug effects , T-Lymphocytes/immunology
6.
J Surg Oncol ; 126(8): 1375-1382, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2013659

ABSTRACT

BACKGROUND AND OBJECTIVES: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a complex treatment used in selected patients with peritoneal surface malignancies. HIPEC procedures are time and resource intensive. The primary aim of this analysis was to compare the experience of treating advanced abdominal tumors with CRS-HIPEC before and during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: Patients included in this analysis received CRS-HIPEC at a single center during either a prepandemic (March 18, 2019-March 17, 2020) or pandemic (March 18, 2020-February 5, 2021) interval. A retrospective chart review was performed. RESULTS: Our analysis included 67 patients: 30 (45%) treated prepandemic and 37 (55%) treated during the pandemic. Median age at the time of operation was 58 years (interquartile range: [49-65]); 53% of patients were women. Patients treated during the pandemic presented with higher peritoneal cancer index (PCI) scores with 32% (n = 12) having a PCI > 20 at the time of surgery (p = 0.01). Five patients had delays in surgery due to the pandemic. Rates of overall postoperative morbidity, reoperation, and readmission were not different between the cohorts. CONCLUSIONS: Despite presenting with more extensive disease, patients treated with CRS-HIPEC during the height of the COVID-19 pandemic had comparable perioperative outcomes to patients treated prepandemic.


Subject(s)
COVID-19 , Hyperthermia, Induced , Peritoneal Neoplasms , Humans , Female , Middle Aged , Male , Cytoreduction Surgical Procedures/adverse effects , Peritoneal Neoplasms/pathology , COVID-19/epidemiology , Hyperthermic Intraperitoneal Chemotherapy , Chemotherapy, Cancer, Regional Perfusion/methods , Pandemics , Retrospective Studies , Feasibility Studies , Hyperthermia, Induced/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Survival Rate , Combined Modality Therapy
7.
Am J Case Rep ; 23: e936536, 2022 Aug 11.
Article in English | MEDLINE | ID: covidwho-2010499

ABSTRACT

BACKGROUND Atezolizumab is an immune checkpoint inhibitor used as first-line treatment with carboplatin and etoposide chemotherapy for advanced small cell lung cancer. Immunochemotherapy treatment decisions can be affected by patients' physical ability. Because of the exclusion of patients with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2 from clinical trials, treatment outcome evidence in this group is limited. CASE REPORT We present the case of a 75-year-old woman with an ECOG PS of 2 admitted with respiratory symptoms and diagnosed with advanced small-cell lung cancer. After managing exacerbation of COPD and decompensated heart failure, atezolizumab with carboplatin and etoposide was administered. After 2 cycles of immunochemotherapy, deterioration of health was observed, including anemia and thrombocytopenia. Because of the good response in imaging tests and restored balance of the patient condition, immunochemotherapy was continued. After 4 cycles of combined treatment, complete regression was achieved. No another adverse effects were observed. The patient was qualified for maintenance therapy with atezolizumab. In follow-up CT scan after 2 cycles of atezolizumab, progression was observed and patient was qualified for second-line treatment. CONCLUSIONS This report presents the case of an older patient with advanced small cell lung cancer and an ECOG status of 2 who responded to combined immunochemotherapy with atezolizumab, etoposide, and carboplatin. Adverse effects observed during immunotherapy were not a reason for discontinuation of the therapy. The assessment of the effectiveness of immunotherapy in patients with ECOG PS ³2 is difficult owing to the insufficient representation of this group in clinical trials.


Subject(s)
Lung Neoplasms , Small Cell Lung Carcinoma , Aged , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carboplatin/therapeutic use , Etoposide/therapeutic use , Female , Group Processes , Humans , Immunotherapy , Lung Neoplasms/drug therapy , Small Cell Lung Carcinoma/drug therapy , Smokers
8.
N Engl J Med ; 386(26): 2482-2494, 2022 06 30.
Article in English | MEDLINE | ID: covidwho-1984509

ABSTRACT

BACKGROUND: Ibrutinib, a Bruton's tyrosine kinase inhibitor, may have clinical benefit when administered in combination with bendamustine and rituximab and followed by rituximab maintenance therapy in older patients with untreated mantle-cell lymphoma. METHODS: We randomly assigned patients 65 years of age or older to receive ibrutinib (560 mg, administered orally once daily until disease progression or unacceptable toxic effects) or placebo, plus six cycles of bendamustine (90 mg per square meter of body-surface area) and rituximab (375 mg per square meter). Patients with an objective response (complete or partial response) received rituximab maintenance therapy, administered every 8 weeks for up to 12 additional doses. The primary end point was progression-free survival as assessed by the investigators. Overall survival and safety were also assessed. RESULTS: Among 523 patients, 261 were randomly assigned to receive ibrutinib and 262 to receive placebo. At a median follow-up of 84.7 months, the median progression-free survival was 80.6 months in the ibrutinib group and 52.9 months in the placebo group (hazard ratio for disease progression or death, 0.75; 95% confidence interval, 0.59 to 0.96; P = 0.01). The percentage of patients with a complete response was 65.5% in the ibrutinib group and 57.6% in the placebo group (P = 0.06). Overall survival was similar in the two groups. The incidence of grade 3 or 4 adverse events during treatment was 81.5% in the ibrutinib group and 77.3% in the placebo group. CONCLUSIONS: Ibrutinib treatment in combination with standard chemoimmunotherapy significantly prolonged progression-free survival. The safety profile of the combined therapy was consistent with the known profiles of the individual drugs. (Funded by Janssen Research and Development and Pharmacyclics; SHINE ClinicalTrials.gov number, NCT01776840.).


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Lymphoma, Mantle-Cell , Adenine/administration & dosage , Adenine/analogs & derivatives , Aged , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bendamustine Hydrochloride/administration & dosage , Bendamustine Hydrochloride/adverse effects , Disease Progression , Humans , Lymphoma, Mantle-Cell/drug therapy , Lymphoma, Mantle-Cell/mortality , Maintenance Chemotherapy , Piperidines/administration & dosage , Piperidines/adverse effects , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Pyrazoles/administration & dosage , Pyrazoles/adverse effects , Pyrimidines/administration & dosage , Pyrimidines/adverse effects , Remission Induction , Rituximab/administration & dosage , Rituximab/adverse effects , Survival Analysis
9.
BMJ Open ; 12(8): e051324, 2022 08 01.
Article in English | MEDLINE | ID: covidwho-1973838

ABSTRACT

INTRODUCTION: Up to one-fifth of patients with colorectal cancer will develop peritoneal metastases, frequently without other districts' involvement. Despite the recent unsuccesses of hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal cancer peritoneal metastases treatment, the rationale in the prophylactic setting remains strong. Several clinical and pharmacokinetic data suggest that the efficacy of intraperitoneal chemotherapy is highest when the disease is microscopic. However, robust evidence demonstrating whether the addition of HIPEC for high-risk colorectal cancers offers better control of local recurrence is lacking. METHODS AND ANALYSIS: This is a multicentre randomised phase 3 trial comparing prophylactic surgery plus HIPEC CO2 with mitomycin, over standard surgical excision in patients with colorectal cancer at high risk of peritoneal carcinomatosis; 388 patients will be included in this study. The primary objective is to compare the efficacy of prophylactic surgery (radical colorectal resection, omentectomy, appendectomy, round ligament of the liver resection and bilateral adnexectomy) plus HIPEC CO2 with mitomycin and standard surgery in terms of local recurrence-free survival. The main secondary endpoints are disease-free survival (DFS), overall survival (OS) and safety. The primary endpoint will be described with a cumulative incidence function and will be analysed with Grey test to take account of the competing risks. DFS and OS will be described with the Kaplan-Meier method. ETHICS AND DISSEMINATION: This trial has been evaluated by the Italian Medicines Agency, local ethics committees and will be submitted to the Ministry of Health to notify the start of the trial according to the regulation of trials on devices with CE mark/certification.The results will be submitted for presentation at academic meetings and for publication in a peer-reviewed journal, whatever the findings. TRIAL REGISTRATION NUMBER: NCT03914820.


Subject(s)
Colorectal Neoplasms , Hyperthermia, Induced , Peritoneal Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carbon Dioxide , Clinical Trials, Phase III as Topic , Colorectal Neoplasms/drug therapy , Combined Modality Therapy , Cytoreduction Surgical Procedures/methods , Female , Humans , Hyperthermia, Induced/methods , Hyperthermic Intraperitoneal Chemotherapy , Mitomycins/therapeutic use , Multicenter Studies as Topic , Peritoneal Neoplasms/secondary , Randomized Controlled Trials as Topic
10.
Thorac Cancer ; 13(18): 2654-2658, 2022 09.
Article in English | MEDLINE | ID: covidwho-1968050

ABSTRACT

Cancer patients are considered highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. However, it is not well known when chemotherapy can be safely restarted in cancer patients after coronavirus disease 2019 (COVID-19). Here, we describe the case of an 18-year-old man diagnosed with primary mediastinal nonseminomatous germ cell tumor (PMNSGCT) in which chemotherapy could be safely restarted after COVID-19. On day 11 of the third cycle of bleomycin, etoposide, plus cisplatin (BEP), he was diagnosed with mild COVID-19. On day 16 after the onset of COVID-19 (day 26 of third cycle of BEP), chemotherapy for his PMNSGCT was restarted. He received surgery after the fourth cycle of BEP without recurrence of COVID-19. Chemotherapy could be restarted and followed by surgery in this post-COVID-19 patient who had experienced mild illness after the discharge criteria were met and all symptoms had disappeared. We report this case with a review of the literature on restarting chemotherapy after SARS-CoV2 infection.


Subject(s)
COVID-19 , Adolescent , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/therapeutic use , Cisplatin/therapeutic use , Etoposide/therapeutic use , Humans , Male , Neoplasms, Germ Cell and Embryonal , RNA, Viral , SARS-CoV-2 , Testicular Neoplasms
11.
Medicine (Baltimore) ; 101(30): e29281, 2022 Jul 29.
Article in English | MEDLINE | ID: covidwho-1967934

ABSTRACT

RATIONALE: Germ cell tumors in the head and neck are very rare. In cases of germ cell tumors, it is uncommon for lymph node metastasis to be the only and initial symptom, and this can easily lead to a misdiagnosis. Herein, we report about a 28-year-old woman with lymph node metastasis, in whom a primary tumor appeared in the nasal cavity. PATIENT CONCERNS: A 28-year-old woman presented with enlarged left submandibular lymph nodes. No other mass was found on whole-body screening using positron emission tomography-computed tomography. DIAGNOSIS: After partial submandibular lymphadenectomy was performed, histopathological and immunohistochemical examinations revealed a metastatic germ cell tumor. However, it was difficult to further classify and affirm the origin. INTERVENTIONS: As the patient was receiving four cycles of bleomycin, etoposide, and cisplatin chemotherapy, a primary tumor emerged in the nasal cavity, which was finally confirmed as an immature teratoma of a high World Health Organization histological grade and Norris grade 3. This tumor was found to contain similar components to lymph nodes with respect to histopathological and immunohistochemical characteristics, especially the immature neural tubes or nervous tissue in the nasal cavity. Fortunately, the patient recovered well with no signs of relapse, and the size of residual lymph nodes remained unchanged after she received another four cycles of bleomycin, etoposide, and cisplatin chemotherapy and two cycles of doxorubicin and ifosfamide (AI) chemotherapy. OUTCOMES: Unfortunately, 11 months later, during the coronavirus disease pandemic, the patient died owing to respiratory failure and pulmonary infection. CONCLUSIONS: In cases of malignant tumor in the submandibular lymph nodes of adults, the metastasis of a germ cell tumor should be considered an important differential diagnosis even if a primary tumor does not emerge. In this case, adequate postoperative chemotherapy is necessary.


Subject(s)
Neoplasms, Germ Cell and Embryonal , Testicular Neoplasms , Adult , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Bleomycin/therapeutic use , Cisplatin/therapeutic use , Etoposide/therapeutic use , Female , Humans , Lymph Node Excision , Lymphatic Metastasis , Male , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Germ Cell and Embryonal/drug therapy , Neoplasms, Germ Cell and Embryonal/therapy , Testicular Neoplasms/pathology
12.
Lancet Oncol ; 23(8): 1078-1086, 2022 08.
Article in English | MEDLINE | ID: covidwho-1915191

ABSTRACT

BACKGROUND: Most kidney transplant recipients with cancer stop or reduce immunosuppressive therapy before starting treatment with an immune checkpoint inhibitor, and approximately 40% of such patients will develop allograft rejection. Isolated immunosuppression reduction might be associated with organ rejection. Whether immunosuppression manipulation, immune checkpoint inhibition, or both, induce organ rejection is difficult to ascertain. The aim of this study was to examine the risk of allograft rejection with immune checkpoint inhibitor exposure when baseline immunosuppression was left unchanged. METHODS: We conducted a multicentre, single-arm, phase 1 study in three hospitals in Australia. Kidney transplant recipients aged 18 years or older with incurable, locally advanced cancer or defined metastatic solid tumours were eligible if they had a creatinine concentration of less than 180 mmol/L, no or low concentrations of donor-specific HLA antibodies, and an Eastern Cooperative Oncology Group status of 0-2. Patients received standard doses of nivolumab (3 mg/kg intravenously every 14 days for five cycles, then 480 mg every 28 days for up to 2 years). The primary endpoint was the proportion of patients with irretrievable allograft rejection and no evidence of tumour response. Primary outcome analyses and safety analyses were done in the modified intention-to-treat population. This trial is registered with the Australian and New Zealand Clinical Trials Register, ANZCTR12617000741381, and is completed. FINDINGS: Between May 31, 2017, and Aug 6, 2021, 22 kidney transplant recipients with various solid tumours were screened and enrolled, four of whom chose not to proceed in the study and one of whom had unexpected disease progression. 17 patients (six [35%] women and 11 [65%] men; median age 67 years [IQR 59-71]) were allocated treatment with nivolumab and were included in the analyses. The trial was then stopped due to ongoing difficulties with running clinical trials during COVID-19 health restrictions. Patients were treated with a median of three infusions (IQR 2-10) and median follow-up was 28 months (IQR 16-34). No patients had irretrievable allograft rejection without evidence of tumour response. There were no treatment-related deaths or treatment-related serious adverse events. The most common grade 3 or grade 4 adverse events were decreased lymphocyte count in four (24%) patients, fever or infection in four (24%) patients, decreased haemoglobin in three (18%) patients, and increased creatinine in three (18%) patients. INTERPRETATION: Maintaining baseline immunosuppression before treatment with an immune checkpoint inhibitor in kidney transplant recipients might not affect expected efficacy and might reduce the risk of allograft rejection mediated by immune checkpoint inhibitors. FUNDING: Bristol Myers Squibb.


Subject(s)
COVID-19 , Kidney Transplantation , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Australia , Creatinine , Female , Humans , Immune Checkpoint Inhibitors/adverse effects , Kidney Transplantation/adverse effects , Male , Nivolumab
13.
Comput Math Methods Med ; 2022: 5430720, 2022.
Article in English | MEDLINE | ID: covidwho-1902135

ABSTRACT

Background: Over the last few years, the role of PDL1/PD-1 in pancreatic cancer development has received increasing attention, and this article is aimed at opening up new ideas for the medicine-based treatment of pancreatic cancer. Aims: To investigate the efficacy and safety of PDL1/PD-1 inhibitors versus FOLFIRINOX regimen in the treatment of advanced pancreatic cancer and its impact on patient survival and to provide a reference basis for clinical treatment of pancreatic cancer. Materials and Methods: The 116 pancreatic cancer patients treated in our hospital from September 2019 to September 2021 were selected and divided into 58 cases each in the (instance of watching, noticing, or making a statement) group and the comparison group according to the method based on random number table. The comparison group was treated with FOLFIRINOX, and the group was treated with PDL1/PD-1 stopper. The effectiveness, safety, and hit/effect on survival of the patients in the two groups were compared. Results: The median chemotherapy cycle for all patients was 4 (1-6), and the combined objective remission rate (0RR) was 36% and the disease control rate (DCR) was 80% after no chemotherapy in 116 patients, with 37.5% 0RR and 81.3% DCR in the observation group and 33.3% 0RR and 77.8% DCR in the comparison group. The greatest number of all patients reached SD, 44%; in the observation group, 43.8%; and in the comparison group, 44.5%. The rate of adverse reactions such as hematological toxicity, neutropenia, anemia, thrombocytopenia, nonhematological toxicity, vomiting, fatigue, infection, diarrhea, intestinal obstruction, and peripheral neuropathy was lower in 10.3% of patients in the observation group than in 25.8% of patients in the comparison group, which was significantly different by χ 2 test (P < 0.05). The median progression-free survival curve of the two groups was 19 months in the comparison group and 22 months in the observation group. The progression-free survival in the observation group was significantly higher than that in the comparison group, and there was a statistically significant difference between the two groups (P < 0.05). Conclusion: PDL1/PD-1 inhibitors in combination with FOLFIRINOX regimens have shown longer survival than treatment with FOLFIRINOX regimens for pancreatic cancer patients, with reliable clinical efficacy, tolerable adverse effects, and a high safety profile for patients.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Pancreatic Neoplasms , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Fluorouracil , Humans , Immune Checkpoint Inhibitors , Irinotecan , Leucovorin , Oxaliplatin , Pancreatic Neoplasms/drug therapy , Programmed Cell Death 1 Receptor
14.
Lancet ; 399(10336): 1718-1729, 2022 04 30.
Article in English | MEDLINE | ID: covidwho-1882652

ABSTRACT

BACKGROUND: Pembrolizumab prolongs progression-free and overall survival among patients with advanced melanoma and recurrence-free survival in resected stage III disease. KEYNOTE-716 assessed pembrolizumab as adjuvant therapy in patients with completely resected, high-risk, stage II melanoma. We report results from the planned first and second interim analyses for recurrence-free survival. METHODS: In this double-blind, randomised, placebo-controlled phase 3 study, involving 160 academic medical centres and hospitals in 16 countries (Australia, Belgium, Brazil, Canada, Chile, France, Germany, Israel, Italy, Japan, Poland, South Africa, Spain, Switzerland, the UK, and the USA), patients aged 12 years or older with newly diagnosed, completely resected stage IIB or IIC melanoma (TNM stage T3b or T4 with a negative sentinel lymph node biopsy) were recruited. Eligible patients were randomly assigned (1:1), in blocks of four and stratified by T-category (3b, 4a, and 4b) and paediatric status (age 12-17 years vs ≥18 years), using an interactive response technology system to intravenous pembrolizumab 200 mg (2 mg/kg in paediatric patients) or placebo every 3 weeks for 17 cycles or until disease recurrence or unacceptable toxicity. All patients, clinical investigators, and analysts were masked to treatment assignment. The primary endpoint was investigator-assessed recurrence-free survival (defined as time from randomisation to recurrence or death) in the intention-to-treat (ITT) population (ie, all patients randomly assigned to treatment). The primary endpoint was met if recurrence-free survival was significantly improved for pembrolizumab versus placebo at either the first interim analysis (after approximately 128 patients had events) or second interim analysis (after 179 patients had events) under multiplicity control. Safety was assessed in all patients randomly assigned to treatment who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, NCT03553836, and is closed to accrual. FINDINGS: Between Sept 23, 2018, and Nov 4, 2020, 1182 patients were screened, of whom 976 were randomly assigned to pembrolizumab (n=487) or placebo (n=489; ITT population). The median age was 61 years (IQR 52-69) and 387 (40%) patients were female and 589 (60%) were male. 874 (90%) of 976 patients were White and 799 (82%) were not Hispanic or Latino. 483 (99%) of 487 patients in the pembrolizumab group and 486 (99%) of 489 in the placebo group received assigned treatment. At the first interim analysis (data cutoff on Dec 4, 2020; median follow-up of 14·4 months [IQR 10·2-18·7] in the pembrolizumab group and 14·3 months [10·1-18·7] in the placebo group), 54 (11%) of 487 patients in the pembrolizumab group and 82 (17%) of 489 in the placebo group had a first recurrence of disease or died (hazard ratio [HR] 0·65 [95% CI 0·46-0·92]; p=0·0066). At the second interim analysis (data cutoff on June 21, 2021; median follow-up of 20·9 months [16·7-25·3] in the pembrolizumab group and 20·9 months [16·6-25·3] in the placebo group), 72 (15%) patients in the pembrolizumab group and 115 (24%) in the placebo group had a first recurrence or died (HR 0·61 [95% CI 0·45-0·82]). Median recurrence-free survival was not reached in either group at either assessment timepoint. At the first interim analysis, grade 3-4 treatment-related adverse events occurred in 78 (16%) of 483 patients in the pembrolizumab groups versus 21 (4%) of 486 in the placebo group. At the first interim analysis, four patients died from an adverse event, all in the placebo group (one each due to pneumonia, COVID-19-related pneumonia, suicide, and recurrent cancer), and at the second interim analysis, one additional patient, who was in the pembrolizumab group, died from an adverse event (COVID-19-related pneumonia). No deaths due to study treatment occurred. INTERPRETATION: Pembrolizumab as adjuvant therapy for up to approximately 1 year for stage IIB or IIC melanoma resulted in a significant reduction in the risk of disease recurrence or death versus placebo, with a manageable safety profile. FUNDING: Merck Sharp & Dohme, a subsidiary of Merck & Co, Kenilworth, NJ, USA.


Subject(s)
COVID-19 , Melanoma , Testicular Neoplasms , Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Double-Blind Method , Female , Humans , Male , Melanoma/drug therapy , Melanoma/surgery , Middle Aged , Neoplasm Recurrence, Local/drug therapy
15.
Support Care Cancer ; 30(9): 7469-7479, 2022 Sep.
Article in English | MEDLINE | ID: covidwho-1877840

ABSTRACT

Autologous stem cell transplantation (ASCT) is standard of care in biologically fit, newly diagnosed multiple myeloma (MM) patients, offering better therapeutic outcomes and improved quality of life (QoL). However, with the UK's 1st national lockdown on 23/03/2020, several guidelines recommended deferring ASCT due to risks of infection, with resource limitations forcing some units to suspend ASCT entirely. Such changes to patients' treatment plans inevitably altered their lived experience during these uncertain times with expected impact on QoL. We conducted a qualitative study using semi-structured interviews to gain insight into MM patients' understanding of their disease, initial therapy and ASCT, and their response to therapy changes. A clinical snapshot of how COVID-19 affected the MM ASCT service in a single UK institution is also provided, including changes to chemotherapy treatment plans, timing, and prioritisation of ASCT. Framework analysis identified 6 overarching themes: (1) beliefs about ASCT, (2) perceptions of information provided about MM and ASCT, (3) high levels of fear and anxiety due to COVID-19, (4) feelings about ASCT disruption or delay due to COVID-19, (5) perceptions of care, and (6) importance of social support. Example subthemes were beliefs that ASCT would provide a long-remission/best chance of normality including freedom from chemotherapy and associated side-effects, disappointment, and devastation at COVID-related treatment delays (despite high anxiety about infection) and exceptionally high levels of trust in the transplant team. Such insights will help us adjust our service and counselling approaches to be more in tune with patients' priorities and expectations.


Subject(s)
COVID-19 , Hematopoietic Stem Cell Transplantation , Multiple Myeloma , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Communicable Disease Control , Humans , Multiple Myeloma/drug therapy , Quality of Life , Retrospective Studies , Stem Cell Transplantation , Transplantation, Autologous
16.
Clin Lab ; 67(11)2021 Nov 01.
Article in English | MEDLINE | ID: covidwho-1818667

ABSTRACT

BACKGROUND: Immunoglobulin D multiple myeloma (IgD-MM) is a rare but aggressive disease. The safety and effectiveness of anti-CD38 monoclonal antibody (daratumumab) have not been known in either IgD-MM or MM complicated with secondary neoplasm. METHODS: A fragile IgD-MM patient had an aggressively relapsed disease concurrent with lung cancer and severe thrombocytopenia, which led to a dilemma for management. After a failure of ixazomib-based chemotherapy, a salvage therapy with daratumumab unexpectedly induced complete remission and platelet recovery, and the patient successfully proceeded to lung cancer surgery. CONCLUSIONS: Our case indicates daratumumab is both safe and effective for refractory IgD-MM with severe complications.


Subject(s)
Lung Neoplasms , Multiple Myeloma , Thrombocytopenia , Antibodies, Monoclonal , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Humans , Immunoglobulin D , Lung Neoplasms/complications , Lung Neoplasms/drug therapy , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Thrombocytopenia/chemically induced , Thrombocytopenia/drug therapy
17.
Medicina (Kaunas) ; 58(4)2022 Apr 03.
Article in English | MEDLINE | ID: covidwho-1810018

ABSTRACT

Dabrafenib and trametinib are two available molecules that have been approved for the treatment of metastatic melanoma with BRAF-V600E or V600K mutations. Their combined therapy has led to long-lasting survival benefits and substantially improved outcomes. Until now, only a few cases of severe hypersensitivity reactions to dabrafenib and vemurafenib have been reported, and even fewer desensitization protocols to these molecules have been documented. We report the case of a 71-year-old female patient with metastatic melanoma harboring a BRAF-V600E mutation undergoing targeted therapy with dabrafenib and trametinib. Two weeks after the initiation of the combined treatment, she developed a hypersensitivity reaction. The cause-effect relationship between dabrafenib and the hypersensitivity reaction was demonstrated twice, when symptoms recurred upon dabrafenib reintroduction. We started a rapid 3-day dabrafenib desensitization protocol, which was well tolerated. When the patient discontinued the drug administration, we decided on a longer protocol that included more steps and more days in order to prevent the occurrence of other hypersensitivity reactions. Our patient tolerated both rapid and slow-going schedules, the first one reaching the final dose within 3 days and the second one reaching the total daily dose within 14 days. Depending on the patient's needs, the severity of the hypersensitivity reaction and the hospital's availability, the doctor may choose either the rapid or slow-going desensitization protocol.


Subject(s)
Melanoma , Neoplasms, Second Primary , Skin Neoplasms , Aged , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Female , Humans , Imidazoles , Melanoma/drug therapy , Melanoma/genetics , Mutation , Neoplasm Recurrence, Local/drug therapy , Neoplasms, Second Primary/etiology , Oximes , Proto-Oncogene Proteins B-raf/genetics , Skin Neoplasms/pathology
18.
Pediatr Blood Cancer ; 69(7): e29713, 2022 07.
Article in English | MEDLINE | ID: covidwho-1782662

ABSTRACT

BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Treatment consists of an initial intensive phase of chemotherapy, followed by a prolonged period of maintenance chemotherapy intended to reduce the risk of relapse. During the COVID-19 pandemic, the need arose to identify and reduce non-essential hospital visits. OBJECTIVE: We aimed to determine which proportion of in-person clinic visits during ALL maintenance therapy was associated with a change of management based on the results of the physical examination. PATIENTS AND METHODS: Medical records of children receiving maintenance chemotherapy for B-precursor ALL between September 2019 and February 2020 were reviewed. Visits with a new finding on physical examination were divided into those where an in-person assessment was deemed essential versus not essential. Finally, we determined the proportion of essential in-person visits that resulted in a change of management. RESULTS: A total of 240 maintenance visits by 75 children were analyzed. An abnormal finding on physical examination was noted during 20 visits (8.3%). Of those, 14 (5.8%) uncovered a new finding, six (2.5%) were classified as "in-person visit essential," and among those six visits, three (1.2%) resulted in a change of patient management (one for acute otitis media, one for wheezing, and one for limp). CONCLUSION: Our findings support the evaluation of care delivery models other than in-person visits during ALL maintenance therapy. A prospective study is required to delineate criteria, benefits/risks, and families' perspectives associated with virtual care delivery and the optimal frequency of in-person visits.


Subject(s)
COVID-19 , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Telemedicine , Ambulatory Care , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Child , Humans , Pandemics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/complications , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy
19.
Front Public Health ; 9: 743558, 2021.
Article in English | MEDLINE | ID: covidwho-1775906

ABSTRACT

Background: As the first domestic PD-1 antibody approved for lung cancer in China, camrelizumab has exhibited proven effectiveness for non-small-cell lung cancer (NSCLC) patients. However, the cost-effectiveness of this new regimen remains to be investigated. Objective: To evaluate the cost-effectiveness of camrelizumab combination therapy vs. chemotherapy for previously untreated patients with advanced, non-squamous NSCLC without Alk or Egfr genomic aberrations from the perspective of China's healthcare system. Methods: Based on the CameL trial, the study developed a three-health state Markov model to evaluate the cost-effectiveness of adding camrelizumab to chemotherapy compared to chemotherapy alone in NSCLC patients. The analysis models were conducted for patients unselected by PD-L1 tumor expression (the base case) and the patient subgroup with PD-L1-expressing tumors (≥1%). Primary model outcomes included the costs in US dollars and health outcomes in quality-adjusted life-years (QALYs) as well as the incremental cost-effectiveness ratio (ICER) under a willingness-to-pay threshold of $31,500 per QALY. Additionally, a scenario analysis that adjusted within-trial crossover was employed to evaluate camrelizumab combination therapy compared to chemotherapy without subsequent use of PD1/PD-L1 antibodies. Results: Camrelizumab combination therapy was more costly and provided additional 0.11 QALYs over chemotherapy in the base case analysis (0.86 vs. 0.75 QALYs), 0.12 QALYs over chemotherapy in the subgroup analysis (0.99 vs. 0.88 QALYs), and 0.34 QALYs over chemotherapy in the scenario analysis (0.86 vs. 0.52 QALYs). Correspondingly, the ICER was $63,080 per QALY, $46,311 per QALY, and $30,591 per QALY, in the base case, the subgroup, and the scenario analysis, respectively. One-way sensitivity analyses revealed that ICERs of the base case and the subgroup analysis were most sensitive to the cost of camrelizumab, the cost of pemetrexed. Besides, the base case and subgroup analysis were more sensitive to the risk of neutrophil count decreased in the camrelizumab and the utility of stable disease, respectively. Conclusion: Although camrelizumab combination therapy is not cost-effective as first-line therapy for NSCLC patients in China in the base case, adjusting within-trial crossover would move the treatment regimen toward cost-effectiveness in the scenario analysis.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/pathology , Cost-Benefit Analysis , Humans , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology
20.
Crit Rev Oncol Hematol ; 172: 103623, 2022 Apr.
Article in English | MEDLINE | ID: covidwho-1748099

ABSTRACT

Daratumumab is approved for newly diagnosed or relapsed/refractory multiple myeloma (MM). The use of daratumumab has improved patient outcomes but has changed the frequency and epidemiology of infections. However, the optimal approach to prophylaxis and supportive therapy for daratumumab-emergent infections is unknown and represents an unmet clinical need in MM. Consequently, an expert panel convened to compose recommendations for optimal infection control in patient candidates to or under daratumumab treatment for MM. Scientific evidence on infections secondary to daratumumab was evaluated, and a consensus was developed by group discussion for key questions selected according to the clinical relevance. The following key issues were addressed: infectious risk assessment and risk stratification, infection mitigation strategies, and management of infectious complications in patients with MM treated with daratumumab.


Subject(s)
Multiple Myeloma , Antibodies, Monoclonal/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Consensus , Humans , Multiple Myeloma/complications , Multiple Myeloma/drug therapy
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