Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) is an autosomal dominant syndrome associated with fumarate hydratase (FH) gene mutation leading to defective DNA double-strand break repair ...mechanism. Although these tumours have an aggressive presentation, they respond well to targeted therapy with fewer adverse effects. Here we present a case of a 42-year-old female having isolated renal cell carcinoma, papillary type 2, carrying a mutation in the FH gene without cutaneous and uterine involvement. Her tumour responded well to erlotinib and bevacizumab combination and she was on treatment for 23 months. This report adds to the current literature and can help to define treatment protocols for HLRCC.
Sinonasal mucosal melanoma is a rare malignancy with limited treatment options and a poor prognosis. They are usually diagnosed at an advanced stage owing to their late and nonspecific clinical ...presentation. Here we present a case of relapsed refractory unresectable malignant melanoma involving the right nasal cavity managed with Oral Metronomic Chemotherapy (OMCT). A 75-year-old male patient was diagnosed with unresectable malignant melanoma involving the right nasal cavity and showed radiological progression after initial management with four cycles of Dacarbazine. He was then shifted to OMCT (Cyclophosphamide, Celecoxib and Tamoxifen), as immunotherapy could not be given due to financial constraints, on which he showed approximately 40% reduction in tumour size after 6 months. This result can have important clinical implications in resource constrained settings, where the use of immunotherapy is limited by great financial burden.
BackgroundSalivary gland tumours are rare cancers with variable course and prognosis. There is a paucity of data, especially for the advanced stages.Materials and methodsThis is a retrospective ...analysis carried out in our institute. All patients seeking treatment for incurable advanced salivary gland tumours from October 2018 to September 2022 were included. Relevant clinical data were collected and appropriate statistical analysis was applied.Results30 patients were included in the analysis. The parotid gland was the most common site of origin (73%). Adenoid cystic carcinoma (ACC) and salivary duct carcinoma (SDC) were equally (37%) the most common pathological subtypes. The majority of patients were males (73%) and lungs (57%) were the most common site of metastases. On molecular analysis, SDC had high rates of androgen receptor (AR) (90%) and human epidermal growth factor receptor 2 (HER2) (55%) positivity. Mucoepidermoid carcinoma (MEC) had AR and HER2 positivity rates of 17% and 20%, respectively, while for ACC it was even lower. A variety of treatment regimens including hormonal therapy, anti-HER2 targeted therapy and chemotherapy were used in first-line treatment. With an overall response rate (ORR) of 10/21 (48%), only 9/21 (43%) went on to receive second-line treatment with an ORR of 4/9 (44%). The progression-free survival (PFS) with first-line treatment (PFS1) was a median of 5 months. The median PFS1 was worst for MEC. The median overall survival (OS) was 10 months. Median OS for ACC, SDC and MEC were 11, 10 and 7 months, respectively. At 24 months, ACC had much higher survival (50%) than others (10%) indicating a proportion of ACC with an indolent course.ConclusionOur analysis highlights the variable disease biology of advanced salivary gland tumours and throws light on the various possible treatment targets and strategies. Molecular profiling and advancement in targeted therapies are expected to increase survival in this group of rare cancers.
Radical cystectomy with bilateral pelvic lymph node dissection is the standard of care for muscle invasive bladder cancer (MIBC). The role of neoadjuvant and adjuvant therapy has evolved over the ...last 3-4 decades, and neoadjuvant chemotherapy (NACT) has now become the standard recommended treatment. However, there are many nuances to this and the utilization of chemotherapy has not been universal. The optimum chemotherapy regimen is still debated. Adjuvant radiation has a role in high-risk patients although not established and immunotherapy has shown promising results. We reviewed the evidence on NACT and adjuvant chemotherapy (ACT) regimens, NACT versus ACT, and the role of adjuvant radiotherapy and immunotherapy in MIBC.
The plasma concentration of 5-Fluorouracil (5-FU) is affected by numerous factors, thereby limiting its efficacy. The current therapeutic regimen's doses based on body surface area (BSA) are linked ...to increased toxicity and sometimes inadequate drug exposure.
The study aims to develop an in-vitro assay to monitor 5-Fluorouracil's therapeutic efficacy in cancer patients' blood samples, focusing on pharmacokinetics to improve therapy precision.
Drug levels were determined from standards, quality controls, and experimental samples using protein precipitation, liquid-liquid extraction, and separation using a C18 analytical column with an isocratic program.
In EXP-1A, the mean concentration of 5-Fluorouracil was 1.15 μg/ml; in EXP-1B, it was 1.16 μg/ml, while in EXP-1C, the mean concentration was 0.9 μg/ml. The percentage difference in mean 5-Fluorouracil concentration between the experiment sample containing a DPD inactivator and EXP-1C (without a DPD inactivator) was 21.5 % higher for EXP-1A and 0.68 % higher for EXP-1B. In the second phase of the experiment, the overall stability of 5-Fluorouracil in samples containing a DPD inactivator was 24.5 % superior compared to samples without a DPD inactivator.
A modified extraction technique has been developed to accurately measure 5-Flourouracil concentration in blood, preserving its stability and concentration by adding a DPD inactivator.
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•Highly sensitive UHPLC method to determine the stability and concentration of 5-FU in plasma.•Extraction technique to determine the concentration of 5-Flourouracil in blood.•Stability is crucial for understanding the drug's performance in Therapeutic Drug Monitoring practices during clinical use and is invaluable for both clinical and pre-clinical studies.•The accurate measurements of 5-FU in the blood are highly influenced in the pre-analytical stage of the samples with presence of DPD enzyme that can be effectively suppressed with the help of specific DPD inactivator like gimeracil.
Novelty. This study represents the initial in-vitro trial assessing the impact of Gimeracil, a specific DPD inactivator, on the stability of the 5-FU drug. It investigates how varying concentrations of the DPD inactivator and different volumes of whole blood affect the stability of the 5-FU drug. Additionally, it aims to elucidate the degradation pattern over time. This data on stability is crucial for understanding the drug's performance in Therapeutic Drug Monitoring practices during clinical use and is invaluable for both clinical and pre-clinical studies.
Background Immunotherapy has improved outcomes in many advanced solid tumors. In resource-constrained settings, less than 2% of patients can afford standard dose immunotherapy. A recent phase II ...study showed the efficacy of low-dose immunotherapy in this setting. We used low-dose immunotherapy on a compassionate basis in patients who had progressed on available standard treatment options and standard dose immunotherapy was not feasible. Patients and Methods We retrospectively collected data from the medical oncology department for consecutive patients who had initially received standard lines of therapy followed by low-dose immunotherapy (nivolumab 40 mg) on a compassionate basis. The demographic details, histology, prior treatment, clinical and radiological response, date of disease progression, date of death, and toxicity data were collected. Results A total of 54 consecutive patients, who received low-dose immunotherapy with nivolumab from January 1, 2018 to February 14, 2020, were included in this analysis; 4 patients were not radiologically evaluable. The median age was 50.4 years (range 35–74 years), male:female ratio was 6:1. The most common comorbidities were hypertension and diabetes seen in 12 (22.2%) and 6 (11.1%) patients, respectively. The majority of the patients (70.4%) were of head and neck cancer. The median follow-up was 4.5 months (range 0.5–11.7). Clinical benefit was observed in 18 (33.3%) patients. Partial response and stable disease were achieved in 9 (16.7%) and 5 (9.3%) patients, respectively. Median survival was not reached for these patients. Six months progression-free survival and overall survival were 100 versus 8.7% (hazard ratio HR 0.05, 95% confidence interval CI: 0.01–0.36; p = 0.003) and 100 versus 29.7% (HR 0.03, 95% CI: 0.00–0.95; p = 0.047), respectively, for responders and nonresponders. The side effects were manageable. Conclusion In resource-constrained settings, low-dose immunotherapy with nivolumab seems to be an effective treatment option. Further studies are warranted to evaluate this approach.
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