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Journal of Pediatric Hematology/oncology Apr 2024Resistant and refractory cytomegalovirus (CMV) viremia can limit the provision of chemotherapy due to myelosuppression and end-organ dysfunction. Few therapies are...
Resistant and refractory cytomegalovirus (CMV) viremia can limit the provision of chemotherapy due to myelosuppression and end-organ dysfunction. Few therapies are available for children with clinically significant CMV viremia. We successfully used maribavir for a 4-year-old patient with lymphoma to complete his chemotherapy course. Resistance to maribavir did result after many months of therapy.
Topics: Child, Preschool; Humans; Antiviral Agents; Benzimidazoles; Cytomegalovirus Infections; Dichlororibofuranosylbenzimidazole; Neoplasms; Ribonucleosides; Viremia
PubMed: 38447094
DOI: 10.1097/MPH.0000000000002841 -
Case Reports in Oncology 2024The introduction of immune checkpoint inhibitors (ICIs) has opened a new chapter in cancer treatment. Nevertheless, their use may result in immune-related adverse events...
INTRODUCTION
The introduction of immune checkpoint inhibitors (ICIs) has opened a new chapter in cancer treatment. Nevertheless, their use may result in immune-related adverse events (irAEs) with multifactorial determinants, complex mechanisms, and varying clinical implications. In specific cancer types, like melanoma, irAEs exhibit a complex relationship with patient outcomes.
CASE PRESENTATION
We present a case of febrile neutropenia following ICI therapy in a patient with metastatic melanoma, underscoring the intricate clinical landscape associated with irAEs in the context of cancer immunotherapy. More specifically, a 68-year-old man was diagnosed with metastatic malignant melanoma and administered a combination of nivolumab and ipilimumab. However, after a single dose, the patient was hospitalized due to febrile neutropenia. The patient eventually recovered, but a diagnosis of myelosuppression related to prior immunotherapy led to treatment discontinuation. Subsequently, the patient transitioned to a second-line therapy.
CONCLUSION
This case contributes to our comprehension of rare yet potentially severe hematological irAEs and their influence on immunotherapy outcomes. Such insights will guide future diagnostic and therapeutic strategies in the field of immunotherapy.
PubMed: 38439907
DOI: 10.1159/000536288 -
Cureus Jan 20245-Fluorouracil (5-FU) and its prodrug, capecitabine, are commonly used chemotherapeutic agents for solid tumor management. While these agents can present with adverse...
5-Fluorouracil (5-FU) and its prodrug, capecitabine, are commonly used chemotherapeutic agents for solid tumor management. While these agents can present with adverse side effects such as nausea, vomiting, diarrhea, and myelosuppression, they can also, less commonly, cause cardiovascular toxicity. This toxicity may manifest as cardiac arrhythmias, myocarditis, heart failure, myocardial infarction, and even death. The management of 5-FU-related cardiotoxicity includes early recognition of symptom manifestation so that medication can be discontinued promptly and symptoms can be addressed appropriately. Here, we describe the case of a 72-year-old male who developed coronary vasospasm and ST-segment elevation myocardial infarction shortly after the initiation of chemotherapy with 5-FU.
PubMed: 38406077
DOI: 10.7759/cureus.52864 -
ESMO Open Apr 2024This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating patients with leptomeningeal metastases (LM) from non-small-cell lung...
BACKGROUND
This study aimed to evaluate the efficacy and safety of intrathecal pemetrexed (IP) for treating patients with leptomeningeal metastases (LM) from non-small-cell lung cancer (NSCLC) who progressed from epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) treatment in an expanded, prospective, single-arm, phase II clinical study (ChiCTR1800016615).
PATIENTS AND METHODS
Patients with confirmed NSCLC-LM who progressed from TKI received IP (50 mg, day 1/day 5 for 1 week, then every 3 weeks for four cycles, and then once monthly) until disease progression or intolerance. Objectives were to assess overall survival (OS), response rate, and safety. Measurable lesions were assessed by investigator according to RECIST version 1.1. LM were assessed according to the Response Assessment in Neuro-Oncology (RANO) criteria.
RESULTS
The study included 132 patients; 68% were female and median age was 52 years (31-74 years). The median OS was 12 months (95% confidence interval 10.4-13.6 months), RANO-assessed response rate was 80.3% (106/132), and the most common adverse event was myelosuppression (n = 42; 31.8%), which reversed after symptomatic treatment. The results of subgroup analysis showed that absence of brain parenchymal metastasis, good Eastern Cooperative Oncology Group score, good response to IP treatment, negative cytology after treatment, and patients without neck/back pain/difficult defecation had longer survival. Gender, age, previous intrathecal methotrexate/cytarabine, and whole-brain radiotherapy had no significant influence on OS.
CONCLUSIONS
This study further showed that IP is an effective and safe treatment method for the EGFR-TKI-failed NSCLC-LM, and should be recommended for these patients in clinical practice and guidelines.
Topics: Humans; Female; Male; Middle Aged; Aged; Carcinoma, Non-Small-Cell Lung; Pemetrexed; Lung Neoplasms; Adult; ErbB Receptors; Injections, Spinal; Prospective Studies; Meningeal Neoplasms; Protein Kinase Inhibitors; Meningeal Carcinomatosis; Treatment Outcome
PubMed: 38377785
DOI: 10.1016/j.esmoop.2024.102384 -
BMC Cancer Feb 2024The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT)...
OBJECTIVE
The aim of this study was to compare the therapeutic value and treatment-related complications of radical hysterectomy with those of concurrent chemoradiotherapy (CCRT) for locally resectable (T1a2-T2a1) stage IIIC1r cervical cancer.
METHODS
A total of 213 patients with locally resectable stage IIIC1r cervical cancer who had been treated at Jiangxi Maternal and Child Health Care Hospital between January 2013 and December 2021 were included in the study and classified into two groups: surgery (148 patients) and CCRT (65 patients). The disease-free survival (DFS) rate, overall survival (OS) rate, side effects, and economic costs associated with the two groups were compared.
RESULTS
43.9% (65/148) patients in the surgical group had no pelvic lymph node metastasis, and 21of them did not require supplementary treatment after surgery due to a low risk of postoperative pathology. The median follow-up time was 46 months (range: 7-108 months). The five-year DFS and OS rates of the surgery group were slightly higher than those of the CCRT group (80.7% vs. 75.1% and 81.6% vs. 80.6%, respectively; p > 0.05). The incidences of grade III-IV gastrointestinal reactions in the surgery and CCRT groups were 5.5% and 9.2%, respectively (p = 0.332). Grade III-IV myelosuppression was identified in 27.6% of the surgery group and 26.2% of the CCRT group (p = 0.836). The per capita treatment cost was higher for the surgery group than for the CCRT group (RMB 123, 918.6 0 vs. RMB 101, 880.90, p = 0.001).
CONCLUSION
The therapeutic effects and treatment-related complications of hysterectomy and CCRT are equivalent in patients with locally resectable stage IIIC1r cervical cancer, but surgery can provide accurate lymph node information and benefit patients with unnecessary radiation.
Topics: Female; Child; Humans; Uterine Cervical Neoplasms; Chemoradiotherapy; Lymph Nodes; Disease-Free Survival; Lymph Node Excision; Retrospective Studies; Neoplasm Staging; Hysterectomy
PubMed: 38360572
DOI: 10.1186/s12885-024-11944-0 -
Cancer Reports (Hoboken, N.J.) Feb 2024Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6-thioguanine nucleosides (6-TGN) are believed...
Assessment on the use of allopurinol to improve safety and efficacy of mercaptopurine in pediatric patients with Acute Lymphoblastic Leukemia and Lymphoma during maintenance therapy.
BACKGROUND
Mercaptopurine is an important component of acute lymphoblastic leukemia (ALL) and lymphoma (LLy) maintenance therapy. The 6-thioguanine nucleosides (6-TGN) are believed to be the primary contributor to myelosuppression and immunosuppressive effects, while 6-methylmercaptopurine (6-MMPN) is believed to be responsible for several toxicities including hepatotoxicity, pancreatitis, and hypoglycemia. Previous reports suggest the addition of allopurinol may reduce these toxicities.
AIMS
To assess the use of allopurinol to improve both safety and efficacy of mercaptopurine in pediatric patients with ALL and LLy during maintenance therapy. Secondary objectives included evaluating patient tolerability and skewed metabolism. In addition, we also analyzed mercaptopurine daily dose reduction upon allopurinol initiation.
METHODS AND RESULTS
The primary endpoint was time within goal ANC prior to and after initiation of allopurinol. Secondary endpoints included; improvement in selective toxicities (hepatotoxicity, pancreatitis, and hypoglycemia) and 6-MMPN to 6-TGN ratio prior to and after allopurinol initiation. In addition, an exploratory endpoint assessing mercaptopurine daily dose reduction prior to and after allopurinol initiation was included. Sixteen patients met inclusion criteria and 15 (94%) of which were included in this study. Median percent of maintenance days within goal ANC prior to and after initiation of allopurinol was 27.8 (IQR 22.6-44.9) and 41.6 (IQR 20.2-58.2) respectively. All patients experienced selective toxicities; 15 (100%) hepatotoxicity, 1 (7%) pancreatitis, and 3 (20%) hypoglycemia. Improvement of toxicities was seen in 13/15 (87%), 1/1 (100%), and 2/3 (67%) respectively. Average 6-MMPN:6-TGN ratio prior to allopurinol initiation was 304:1 and after, allopurinol initiation improved to 15:1, resulting in a 95% reduction. Average mercaptopurine dose prior to and after allopurinol initiation decreased by about 56% (63 to 28 mg/m /day).
CONCLUSION
Results suggest that the use of allopurinol in pediatric patients with ALL and LLy receiving mercaptopurine during maintenance therapy is both safe and effective.
Topics: Humans; Child; Mercaptopurine; Allopurinol; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Hypoglycemia; Drug-Related Side Effects and Adverse Reactions; Chemical and Drug Induced Liver Injury; Lymphoma; Pancreatitis
PubMed: 38351548
DOI: 10.1002/cnr2.1987 -
Oncology Letters Mar 2024Atypical teratoid rhabdoid tumor (ATRT) is a rare type of potentially fatal childhood brain tumor. The present study aimed to examine the overall survival (OS) and...
Atypical teratoid rhabdoid tumor (ATRT) is a rare type of potentially fatal childhood brain tumor. The present study aimed to examine the overall survival (OS) and event-free survival (EFS) outcomes of pediatric patients with ATRT and to analyze the impact of different prognostic factors, including age, sex, tumor site and size, metastatic disease, the extent of resection, radiotherapy, and chemotherapy, on survival. The present study included 47 patients with ATRT treated at the Children's Cancer Hospital of Egypt (Cairo, Egypt) between July 2007 and December 2017. These patients were treated according to the Dana-Farber Cancer Institute protocol 02-294 for 51 weeks. Various prognostic factors, including age, sex, tumor size and initial metastatic status, exhibited no impact on the radiological response measured at 6 weeks and at the end of treatment. The primary tumor site significantly affected the response to treatment at 6 weeks (P=0.008). Toxicity-related mortality occurred in 29.8% of patients. The median duration of the treatment protocol was 66.9 weeks. The duration of treatment was in the present cohort was longer than the actual 51 weeks of the protocol due to prolonged supportive care of the included patients. Patients who encountered toxicity received reduced dose of chemotherapy in the subsequent cycles in the protocol. Age, initial metastatic status, tumor site and resection extent did not significantly affect the patient outcomes. Preoperative tumor size significantly affected the EFS (P=0.03) and OS (P=0.04). Radiotherapy administration significantly affected the OS (P<0.001) and EFS (P<0.001). The median EFS and OS of patients were 9.3 and 10.3 months, respectively. A total of 24 (51.1%) patients exhibited disease progression or recurrence. The progression sites were local (n=6), metastatic (n=9) or both local and metastatic (n=9). The results of the present study demonstrated that the therapeutic regimen should be patient-adjusted to maintain the treatment intensity and avoid toxicity-related mortality. In lower middle-income countries, short and intensified induction followed by consolidation of treatment, either by single or tandem autologous stem cell transplant, is needed to avoid prolonged exposure to myelosuppression and toxicity-related mortality.
PubMed: 38348388
DOI: 10.3892/ol.2024.14263 -
Neuro-oncology Advances 2024Recurrent glioblastoma (rGBM) has limited treatment options. This phase 1 protocol was designed to study the safety and preliminary efficacy of TPI 287, a central...
BACKGROUND
Recurrent glioblastoma (rGBM) has limited treatment options. This phase 1 protocol was designed to study the safety and preliminary efficacy of TPI 287, a central nervous system penetrant microtubule stabilizer, in combination with bevacizumab (BEV) for the treatment of rGBM.
METHODS
GBM patients with up to 2 prior relapses without prior exposure to anti-angiogenic therapy were eligible. A standard 3 + 3 design was utilized to determine the maximum tolerated dose (MTD) of TPI 287. Cohorts received TPI 287 at 140-220 mg/m every 3 weeks and BEV 10 mg/kg every 2 weeks during 6-week cycles. An MRI was performed after each cycle, and treatment continued until progression as determined via response assessment in neuro-oncology criteria.
RESULTS
Twenty-four patients were enrolled at 6 centers. Treatment was generally well tolerated. Fatigue, myelosuppression, and peripheral neuropathy were the most common treatment emergent adverse events. Dose-limiting toxicity was not observed, thus the MTD was not determined. Twenty-three patients were evaluable for median and 6-month progression-free survival, which were 5.5 months (mo) and 40%, respectively. Median and 12-month overall survival were 13.4 mo and 64%, respectively. The optimal phase 2 dose was determined to be 200 mg/m.
CONCLUSIONS
TPI 287 can be safely combined with BEV for the treatment of rGBM and preliminary efficacy supports further investigation of this combination.
PubMed: 38327681
DOI: 10.1093/noajnl/vdae009 -
Cancer Management and Research 2024Therapeutic regimens are relatively scarce among patients with treatment-refractory metastatic colorectal cancer (CRC). This study aimed to determine the feasibility and...
OBJECTIVE
Therapeutic regimens are relatively scarce among patients with treatment-refractory metastatic colorectal cancer (CRC). This study aimed to determine the feasibility and tolerability of anlotinib plus PD-1 blockades in patients with treatment-refractory metastatic CRC retrospectively.
METHODS
A total of 68 patients with previously treated metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in this study retrospectively. Demographic and clinical characteristics of the patients, therapeutic outcomes and safety profile during administration were collected and briefly analyzed. All subjects were followed up regularly. Therapeutic outcomes, including drug response and prognosis, were presented, and a safety profile was depicted to illustrate the adverse reactions.
RESULTS
A total of 68 patients with treatment-refractory metastatic CRC who received anlotinib plus PD-1 blockades in clinical practice were included in the final analysis. Best therapeutic response during treatment indicated that partial response was observed in 11 patients, stable disease was noted in 41 patients, and progressive disease was found in 16 patients, producing an objective response rate of 16.2% (95% CI: 8.4%-27.1%) and a disease control rate of 76.5% (95% CI: 64.6%-85.9%). Prognostic analysis suggested that the median progression-free survival (PFS) of the 68 patients was 5.3 months (95% CI: 3.01-7.59), and the median overall survival (OS) was 12.5 months (95% CI: 9.40-15.60). Of the 11 patients who responded, the median duration of response was 6.7 months (95% CI: 2.89-10.53). Safety profile during treatment showed that patients experienced adverse reactions regardless of grade, and grade ≥3 adverse reactions were found in 61 patients (89.7%) and 41 patients (60.3%), respectively. Common adverse reactions were hypertension, myelosuppression (including leukopenia, neutropenia, thrombocytopenia, and anemia), fatigue, and hand-foot syndrome.
CONCLUSION
Anlotinib plus PD-1 blockades demonstrated encouraging efficacy and acceptable safety profile in patients with treatment-refractory metastatic CRC preliminarily in clinical practice. This conclusion should be confirmed in prospective clinical trials.
PubMed: 38318097
DOI: 10.2147/CMAR.S427680