Ribociclib-induced hepatotoxicity Er, Muhammed Muhiddin; Araz, Murat; Hendem, Engin ...
Journal of oncology pharmacy practice,
07/2023, Letnik:
29, Številka:
5
Journal Article
Recenzirano
Introduction
Cyclin-dependent kinase (CDK) 4/6 inhibitors have shown a different adverse effect. In this case, persistent grade 3 hepatoxicity was observed after ribociclib. Therefore, ribociclib ...therapy was stopped, and then palbociclib was introduced. Transaminase levels returned to normal by switching to palbociclib therapy.
Case report
71-year-old postmenopausal female patient with luminal subtypes of metastatic breast cancer treated with ribociclib.
Management & outcome
Grade 3 hepatotoxicity secondary to ribociclib developed. She was successfully treated with palbociclib 125 mg.
Discussion
In our case, palbociclib was started with a full dose, to increase treatment success. Starting with a 125 mg dose was not cause any toxicity. Nevertheless, laboratory follow-up is required in terms of neutropenia and increased transaminases.
Background
Atezolizumab (ATZ) has demonstrated antitumor activity in previous studies in patients with metastatic platinum-resistant urothelial carcinoma. However, the response rate of ATZ was ...modest. Therefore, finding biologic or clinical biomarkers that could help to select patients who respond to the immune checkpoint blockade remains important.
Patients and methods
In this study, we present the retrospective analysis of 105 patients with urothelial cancer treated with ATZ after progression on first-line chemotherapy. Data of patients were obtained from patient files and hospital records. The association between response to first-line chemotherapy and ATZ was using Fisher’s exact test. Median follow-up was calculated using the reverse Kaplan–Meier method. OS was estimated by using the Kaplan–Meier method.
Results
The median follow-up time was 23.5 months. Forty (74.1%) of patients who experienced clinical benefit after firs-line chemotherapy also had clinical benefit after atezolizumab, while only 14 (25.9%) of patients with initial PD after first-line chemotherapy subsequently experienced clinical benefit with ATZ (
p
= 0.001). The median OS on ATZ of 14.8 and 3.4 months for patients with clinical benefit and progressive disease in response to first-line chemotherapy, respectively (
p
= 0.001). Three of the adverse prognostic factors according to the Bellmunt criteria were independent factors of short survival: liver metastases {Hazard ratio HR = 1.9;
p
= 0.04}, ECOG PS ≥ 1 (HR = 2.7;
p
= 0.001), and Hemoglobin level below 10 mg/dl (HR = 2.8;
p
< 0.001). In addition, patients with clinical benefit from first-line chemotherapy (HR = 0.39;
p
< 0.001) maintained a significant association with OS in multivariate analysis.
Conclusions
Our study demonstrated that clinical benefit from first-line chemotherapy was independent prognostic factors on OS in patients’ use of ATZ as second-line treatment in metastatic bladder cancer. Furthermore, these findings are important for stratification factors for future immunotherapy study design in patients with bladder cancer who have progressed after first-line chemotherapy.
Background
The prognostic value of perineural invasion (PNI) in head and neck squamous cell carcinoma (HNSCC) remains controversial. This study investigated the impact of PNI on prognosis in HNSCC. A ...total of 49 patients with HNSCC who underwent primary surgical treatment were selected for the study. Univariate analysis of the survival curve was performed using the Kaplan-Meier method. Multivariate analysis was carried out by Cox regression.
Results
PNI was present in 17 of 49 (34.7%) patients. The median follow-up was 18.7 months. The median DFS and OS were 16.6 months and 41.9 months, respectively. Univariate analyses showed that PNI was associated with OS (
p
: 0.02), but not with DFS (
p
: 0.50). ENE was associated only with DFS in univariate analysis (
p
: 0.04), but not OS (yes vs. no; 24.1 vs. 44.6 months,
p
: 0.21), and in multivariate analysis, ENE lost its significance for DFS (
p
: 0.12). Also, PNI was the only significant independent adverse prognostic factor for OS in multivariate analysis (
p
: 0.02). The median OS for patients with and without PNI was 17.1 months and 92.1 months, respectively.
Conclusion
PNI was an independent factor for poor prognosis in patients with HNSCC. The presence of PNI compared to ENE was associated with a greater risk of death in HNSCC. Therefore, it would be appropriate to consider adjuvant therapy in the presence of PNI alone without other adverse risk features.
Introduction
Leukocytoclastic vasculitis is a histopathological term describing vasculitis in which the inflammatory infiltrate in small vessels consists of neutrophils. Although FLOT is given ...perioperatively in locally advanced, resectable gastric or gastroesophageal junction adenocarcinoma, it has recently become a popular treatment option for metastatic cancers. In this case report, we present a case of FLOT-induced LCV.
Case Report
We present a 52-year-old patient with metastatic gastric adenocarcinoma treated with FLOT. The patient developed necrotizing vasculitis in the lower extremity after 5 cycles of FLOT.
Management & Outcome
After discontinuation of the FLOT regimen, the necrotizing morbid LCV gradually regressed with steroid therapy.
Discussion
To the best of our knowledge, our case is the first case of LCV that developed after FLOT chemotherapy. The clinical appearance of the patient, occurrence after chemotherapy, erythematous rash developing on bilateral lower extremities, and palpable purpuric vasculitis made us suspect. We found a potential relationship between FLOT and vasculitis according to the Naranjo scale (score 4 + ).
Introduction
Cetuximab, an anti-EGFR monoclonal antibody, often cause skin toxicity, most commonly acneiform rash. We present a rare case of glomerulonephritis associated with cetuximab therapy.
Case ...Report
A 58-year-old male patient recently completed cetuximab-based chemotherapy for metastatic colorectal adenocarcinoma. He presented with acute renal failure, anasarca edema and nephrotic proteinuria. The amount of protein in the 24-h urine test was over 15.6 grams.
Management & Outcome
The patient showed a dramatic improvement in renal function shortly after terminated of cetuximab therapy without immunosuppressive therapy.
Discussion
Therefore, drugs targeting epidermal growth factor receptor (EGFR) monoclonal antibody were thought to trigger nephrotic syndrome by causing glomerular damage. As a result, physicians using EGFR monoclonal inhibitors should be very careful about renal functions and proteinuria in patients.
Purpose
Febrile neutropenia resulting from chemotherapy is a significant cause of morbidity and mortality in cancer patients. We had previously published the associates of the risk of febrile ...neutropenia, and this study now extends and modifies the previous model as well as tests its external validity.
Methods
We have recruited documented febrile neutropenia cases with solid tumors, in addition to a selected control group of cancer patients from one institution treated between 2015 and 2019. We then united our sample with our previously published original derivation group, to modify and update our previous model by logistic regression analysis. Additionally, consecutive cancer patients from 5 institutions were recruited in 2020 to test external validity of the resultant algorithm.
Results
A total of 4075 cycles of chemotherapy in 1282 cases were recruited in the updated, new model derivation group, and a total of 8 variables were selected for the updated algorithm. In the new external validation group, 653 cycles of chemotherapy in 624 patients were analyzed, to indicate that after cycles without prophylactic granulocyte colony-stimulating factor (GCSF) usage, the algorithm yielded a sensitivity value of 91%, specificity of 40%, and an area under curve (AUC) figure of 0.78, when a risk cutoff threshold value of ≥ 0.20 is chosen. This algorithm is now embedded in a web application for free clinical use.
Conclusion
Our algorithm identifies and quantifies the risk of febrile neutropenia in cancer patients. Further studies are required to improve this model with additional predictors.
Purpose
In this study, we looked for whether treatment-induced rash predicts treatment efficacy in patients with recurrent/metastatic HNSCC treated with Cetuximab and chemotherapy.
Methods
Patients ...who were treated with platinum-based chemotherapy and cetuximab for the first line treatment of recurrent/metastatic HNSCC were recruited. Presence of rash, hypomagnesemia, hypopotassemia, anemia, neutropenia, thrombocytopenia during treatment and treatment response, date of progression, date of last visit and death were recorded.
Results
A total of 138 patients’ data were available for analysis. Any grade of rash was detected in 57 (44.5%) of the patients. The incidence of rash was significantly higher in patients with objective response than in patients with disease progression (%56.8 vs %14.3,
p
< 0.001). Progression free survival was 7.06 months (4.98–9.15) in patients treated with cetuximab and chemotherapy as first line treatment. In the multivariate analysis; rash was significantly correlated with longer PFS (HR 2.136; 95% CI 1.067–4.278;
p
= 0.032). Progression free survival was 9.65 months in patients who experienced rash, and 6.02 months in patients without rash, (
p
= 0.019, log-rank test). Overall survival was 11.24 months (9.65–12.82). In multivariate analysis, the survival of patients with rash was significantly longer than patients without rash (HR 1.954; 95% CI 1.162–3.285;
p
= 0.012). Overall survival was 15.08 months in patients who experienced rash, and 8.61 months in patients without rash (
p
= 0.05, log-rank test).
Conclusion
Cetuximab-induced rash is associated with better ORR and longer PFS and OS in patients with recurrent/metastatic HNSCC treated with Cetuximab and platinum-based chemotherapy.
Introduction
Regorafenib, a receptor tyrosine kinase inhibitor, is a routinely used targeted agent in the current treatment of patients with refractory metastatic colorectal carcinoma (mCRC). The ...aims of this study were to detect the presence of bowel wall edema during regorafenib treatment via computed tomography (CT) and to assess the relationship between survival and regorafenib-induced bowel wall edema in patients with mCRC receiving regorafenib.
Patients and methods
We retrospectively evaluated the presence of bowel wall edema on CT of 25 mCRC patients who received regorafenib and analyzed its relationship with progression free survival (PFS) and overall survival (OS).
Results
Among the 25 patients, 25 had small bowel wall edema (SBWE) and 14 had large bowel wall edema (LBWE) on at least one CT examination. The median SBWE value was 4.85 milimeters (mm). Of the 25 patients, 14 had SBWE ≤4.85 mm and 11 had SBWE >4.85 mm. Regorafenib intolerance was significantly higher at SBWE >4.85 mm patients (p = 0.03). The median PFS was 4.6 months (95% CI: 2.4–6.8) and median OS was 9.3 months (95% CI: 3.1–15.4). Median PFS and OS were shorter in patients with SBWE > 4.85 mm than in those with ≤4.85 mm, but not statistically significant (median PFS: 3.9 vs 4.6 months, p: 0.523; median OS: 5.6 vs 9.3 months, p: 0.977).
Conclusions
Regorafenib caused SBWE in patients with mCRC. Patients who developed more SBWE had a higher regorafenib intolerance and a shorter survival. Further studies are needed to confirm the predictor value of SBWE on the survival outcomes of patients with mCRC receiving regorafenib.
Introduction
Pazopanib is an agent that is being successfully used in soft tissue sarcomas. Some endocrine side effects may develop during pazopanib treatment. Here, we presented a case diagnosed ...with secondary adrenal insufficiency while being investigated for etiology of hypoglycemia which developed after pazopanib.
Case report
A 69-year-old male patient was operated in June 2019 due to a lung mass 26 × 18 × 10 cm in size. Pathological diagnosis revealed a solitary fibrous tumor with malignant behavior. The patient received three lines of chemotherapy. After pazopanib treatment, a hypoglycemic attack was reported.
Management and outcome: Blood cortisol and ACTH (Adrenocorticotropic hormone) levels were not increased at the time of the hypoglycemic attack, and levels of other pituitary hormones were found to be normal. Electrolyte levels were in normal range. Since the counteracting hormone did not reach a sufficient level, it was considered secondary adrenal insufficiency. Hypoglycemic attacks did not occur during follow-up while taking steroid therapy and pazopanib.
Discussion
A single case of primary adrenal insufficiency has been reported in the literature. We here present a case who developed hypoglycemia after pazopanib and was diagnosed with drug-associated secondary adrenal insufficiency. When hypoglycemia develops during pazopanib treatment, we must be aware of adrenal insufficiency.
Background
We aimed to investigate the effect of radiological complete response on survival outcomes in patients with non-metastatic nasopharyngeal cancer. This study is conducted as a retrospective ...cohort. Of the 185 patients screened, 60 were metastatic, 25 patients’ data was not available, and as a result, 92 patients were included in the study. Among the complete response (CR) and incomplete response (IR) groups, overall survival (OS), distant metastasis-free survival (DMFS), and locoregional failure-free survival (LRFFS) were evaluated.
Results
Of the 92 patients, 54 (58.6%) were CR and 38 (41.4%) were IR patients. Of the whole study group, the 5-year OS, DMFS, and LRFFS rates were 75%, 78%, and 95%, respectively. A significant difference was found between the 5-year OS (90% vs. 60%,
p
= 0.001) and DMFS (87% vs. 65%,
p
= 0.02) rates. However, there was no significant difference in the 5-year LRFFS rate (97% vs. 92%,
p
= 0.16). Complete response were determined as an independent predictor for OS (HR: 0.13, 95% Cl: 0.045–0.36,
p
< 0.001) and DMFS (HR: 0.26, 95% CI: 0.095–0.744,
p
= 0.012).
Conclusion
As a result, the survival benefit in patients with CR after primary treatment is evident as shown in the above studies. Therefore, the aim of primary treatment should be to increase the CR rates. It is important to evaluate early tumor response to determine poor tumor regression.
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