scholarly journals Severe pancytopenia caused by trifluridine/tipiracil in patients with metastatic colorectal cancer and an impaired renal function: A case report

2021 ◽  
Author(s):  
Masatsune Shibutani ◽  
Yuki Okazaki ◽  
Shinichiro Kashiwagi ◽  
Hisashi Nagahara ◽  
Tatsunari Fukuoka ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Renal Function ◽  
Case Report ◽  
Adverse Events ◽  
Renal Impairment ◽  
Metastatic Colorectal Cancer ◽  
Impaired Renal Function ◽  
Hematological Toxicity ◽  
Severe Adverse Events ◽  
Severe Pancytopenia

Although the incidence of hematological toxicity due to FTD/TPI treatment is high, the incidence of severe adverse events has been reported to be relatively low. However, it should be noted that patients with renal impairment are prone to severe hematological adverse events.

A Phase I Open-Label Trial To Determine the Pharmacokinetics of Glucarpidase in Subjects with Normal and Impaired Renal Function.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4450-4450
Author(s):  
Marc A. Phillips ◽  
Tim R. Auton ◽  
Suzanne B. Ward ◽  
William B. Smith ◽  
Guhan Balan
Keyword(s):  
Renal Function ◽  
Adverse Events ◽  
Renal Impairment ◽  
Creatinine Clearance ◽  
Normal Renal Function ◽  
Impaired Renal Function ◽  
Prolonged Exposure ◽  
The Body ◽  
Calculated Creatinine Clearance ◽  
The Mean

Abstract Methotrexate (MTX) is used in high doses in the treatment of cancers such as NHLs, leukemias and osteosarcoma. In some patients it produces renal damage which delays its elimination from the body. Prolonged exposure to high concentrations of MTX results in serious toxic effects. Glucarpidase (Voraxaze™, formerly carboxypeptidase G2) contains a recombinant enzyme which rapidly and predictably breaks down MTX in the blood within 15 minutes of administration. Multiple studies to date have evaluated glucarpidase as an intervention for patients at risk or experiencing toxicities related to MTX overexposure. Continuing studies seek to evaluate the use of glucarpidase in a planned way to circumvent toxicity and prevent prolonged hospitalization. The current study examined the pharmacokinetics of glucarpidase in subjects who had both normal and severely impaired renal function, similar to that of the intended patient population. Methods: Twelve male and female subjects participated in this study; 8 with normal renal function (calculated creatinine clearance >80 mL/min) and 4 with severely impaired renal function (calculated creatinine clearance <30 mL/min). Each subject received a single intravenous dose of glucarpidase 50 units/kg (equivalent to 114.5 μg/kg), infused over 5 min. Serum glucarpidase profiles were evaluated for all subjects using 7 mL blood samples collected at the following time points: pre-dose (prior to start of glucarpidase IV dose), end of 5-minute infusion, and 0.25, 0.5, 1, 2, 4, 6, 8, 12, 18, 24, 48, 72, and 96 hours following the start of the infusion. The study protocol was approved by the Crescent City Institutional Review Board IRB (New Orleans, LA) and all subjects gave their written informed consent prior to inclusion in the study. Results: The mean (SD) Cmax for glucarpidase in renally impaired subjects was 2.9 μg/mL (0.83), the mean half-life was 10.0 (2.1) h and mean AUC0-∞ was 24.5(9.4) μg.h/mL. Similar values were found in subjects with normal renal function (mean Cmax 3.1 μg/mL, mean t1/2 9.0 h and mean AUC0-∞ 23.4 μg.h/mL). No adverse events were recorded in the study. Conclusions: The results indicated little effect of renal impairment on the serum pharmacokinetics of glucarpidase. Evaluations of adverse events, clinical laboratory assessments, vital signs, ECGs, and physical examinations indicated that a single 50 unit/kg dose of glucarpidase was safe and well-tolerated when administered to subjects with normal renal function and subjects with severe renal impairment. PK parameters found in this study may be relevant to cancer patients treated with 50 units/kg glucarpidase, including those with MTX-induced renal toxicity.

Plasma concentrations of 5-FU and creatinine clearance as predictive markers for severe toxicities of capecitabine in patients with colorectal cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 428-428
Author(s):  
Katsuya Makihara ◽  
Hideyuki Mishima ◽  
Sayaka Azuma ◽  
Kazuyo Miyagi ◽  
Katsuya Komori ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Renal Function ◽  
Plasma Concentration ◽  
Adverse Events ◽  
Creatinine Clearance ◽  
Plasma Concentrations ◽  
Predictive Markers ◽  
Characteristic Analysis ◽  
Severe Adverse Events ◽  
Grade 3

428 Background: Pharmacokinetically guided dose adjustment of 5-fluorouracil (5-FU) are available but management of capecitabine has not been established. Patients with renal impairment often experience severe adverse events. The aim of this study is to assess the relationship between plasma concentration of 5FU, metabolites after administration of capecitabine, renal function and adverse events. Methods: Plasma concentration–time data for capecitabine, 5’-DFUR, 5’-DFCR and 5-FU were analyzed by blood samples within 60–180 min after administration of capecitabine on day 8 in colorectal cancer patients receiving capecitabine based regimen (capecitabine with or without oxaliplatin and bevacizumab). Concentrations of 5-FU were analized by a nanoparticle antibody-based immunoassay for 5-FU(My 5-FUR assay). Correlation between the peak concentration of capecitabine metabolites (Cmax) or creatinine clearance (Ccr) and toxicity (grade 3–4 diarrhea, grade 2-3 hand–foot syndrome and grade 3–4 anorexia) were assessed. When parameter of correlation exists, logistic regression analysis was done. ROC (receiver operating characteristic) analysis was conducted to explore the cut off value of the parameter associated with severe adverse events. Results: A total of 42 patients were analyzed. The Cmax of 5’-DFUR, 5-FU and Ccr were significantly correlated with the incidence of severe adverse events. Cmax of 5-FU (p = 0.015) and Ccr (p = 0.016) were also independent parameters. According to the ROC analysis, severe adverse events were observed in the patients whose Cmax of 5-FU was higher than 295 ng/mL and Ccr was lower than 64.8 mL/min. Conclusions: Plasma concentration of 5-FU and renal function are good predictive markers of adverse events after capecitabine administration. These results would lead to the appropreate indivisual dosage adjustment of capecitabine.

Anti-PD-1 and regorafenib induce severe multisystem adverse events in microsatellite stability metastatic colorectal cancer: a case report

Immunotherapy ◽  
2021 ◽  
Author(s):  
Yuchen Yang ◽  
Lingyan Xu ◽  
Danping Wang ◽  
Bingqing Hui ◽  
Xiaofei Li ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Case Report ◽  
Adverse Events ◽  
Metastatic Colorectal Cancer ◽  
Tumor Shrinkage ◽  
Line Treatment ◽  
Third Line ◽  
Grade 3 ◽  
Microsatellite Stability ◽  
Third Line Treatment

There exists a dilemma in the treatment of microsatellite stability (MSS) metastatic colorectal cancer (mCRC) owing to limited therapeutic options. Based on the promising results of the REGONIVO trial, combination of anti-PD-1 and regorafenib could be applicable for this kind of patients. Here we first report a case of an MSS mCRC patient who received sinitilimab plus regorafenib as third-line treatment and suffered severe multisystem treatment-related adverse events including Grade 3 myocarditis, myositis, myasthenia gravis, dermatitis, hepatitis, etc. Fortunately, all these adverse events have been reversed with administration of corticosteroids. Though evidence of tumor shrinkage was not found, CEA levels markedly decreased. Therefore, anti-PD-1 plus regorafenib might be optional for the MSS mCRC patients which requires special caution in the clinical practice.

scholarly journals The Role of Dynamic ctDNA Monitoring During Combination Therapies of BRAF V600E-Mutated Metastatic Colorectal Cancer: A Case Report

2020 ◽  
Vol Volume 13 ◽  
pp. 11849-11853
Author(s):  
Zhan Wang ◽  
Chen-Yang Ye ◽  
Wen-Li Zhou ◽  
Miao-Miao Wang ◽  
Wei-Ping Dai ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Case Report ◽  
Metastatic Colorectal Cancer ◽  
Braf V600e ◽  
Combination Therapies

The association of renal function with safety and efficacy of cisplatin plus S-1 (CS) therapy and docetaxel plus cisplatin plus S-1 (DCS) therapy in patients with advanced gastric cancer (AGC): An additional analysis of JCOG1013.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16035-e16035
Author(s):  
Shuichi Hironaka ◽  
Ryo Sadachi ◽  
Nozomu Machida ◽  
Satoru Iwasa ◽  
Yasuhide Yamada ◽  
...  
Keyword(s):  
Renal Function ◽  
Adverse Events ◽  
Objective Response ◽  
Exploratory Analysis ◽  
Phase Iii ◽  
Fixed Dose ◽  
Hematological Toxicity ◽  
Significant Difference ◽  
Group A ◽  
Group B

e16035 Background: A phase III study, JCOG1013, did not show the superiority of docetaxel plus cisplatin plus S-1 (DCS) to cisplatin plus S-1 (CS) in overall survival (OS) (Yamada Y, Lancet GH 2019). It is known that cisplatin and gimeracil (an inhibitor of dihydropyrimidine dehydrogenase contained in S-1) are excreted in urine. We previously reported (abstr 197, ASCO-GI 2021) exploratory analysis of JCOG1013 which showed creatinine clearance (CrCl) was associated with safety (Grade [G]4 hematological toxicity for CS, and G3-4 non-hematological toxicity for CS and DCS), but not with efficacy in either group. Here, we report the additional detail results of this exploratory analysis. Methods: Among 741 participants in JCOG1013, patients with serum creatinine level < 1.2 mg/dL were included in this analysis and categorized by CrCl and treatment into A1 (CrCl ≥ 80 mL/min, CS), A2 (60 < CrCl < 80, CS), A3 (CrCl < 60, CS), B1 (CrCl > 80, DCS), B2 (60 < CrCl < 80, DCS), and B3 (CrCl < 60, DCS). The dose (mg/m2) of C/S was 60/80 regardless renal function in group A (A1, A2 and A3), and that of D/C/S was adjusted in group B as follows: 40/60/80 in B1, 40/50/80 in B2, and 40/40/65 in B3. Adverse events, OS, progression-free survival (PFS), and objective response rate (ORR) were compared by CrCl in group A (A1 vs. A2 vs. A3) and group B (B1 vs B2 vs B3), respectively. Results: Of 723 pts (169/136/57 in A1/A2/A3 and 170/138/53 in B1/B2/B3), the median CrCl (mL/min) was 94.1/71.9/53.4 in A1/A2/A3 and 98.2/70.0/55.6 in B1/B2/B3. The relative dose intensity of C/S was 90.4/75.3%, 87.8/74.9% and 85.7/72.8% in A1, A2 and A3, and that of D/C/S was 87.5/77.7/74.9%, 85.8/61.2/72.7% and 87.8/49.4/58.3% in B1, B2 and B3. The incidence of G4 white blood cell decreased, G4 neutrophil count decreased, and G3-4 anorexia were 1.2/4.4/9.3% (P < 0.01), 4.8/11.1/18.5% (P < 0.01), 14.4/28.1/28.6% (P < 0.01) in A1/A2/A3, and 1.8/3.0/4.0% (P = 0.36), 27.3/24.8/20.0% (P = 0.28), 22.4/29.3/32.0% (P = 0.11) in B1/B2/B3, respectively. No significant association between CrCl and other adverse events was observed either in CS or in DCS group. The median OS was 15.4/15.5/15.4 months in A1/A2/A3 (P = 0.89) and 15.3/13.7/13.7 months in B1/B2/B3 (P = 0.72). The median PFS was comparable among A1/A2/A3 (7.1/6.8/6.2 months, P = 0.88) and B1/B2/B3 groups (7.5/7.2/7.8 months, P = 0.85). ORR showed no significant difference in A1/A2/A3 (58.9/57.8/46.9%, P = 0.31) and B1/B2/B3 groups (62.0/61.5/51.5%, P = 0.36). Conclusions: Dose modification according to renal function in the DCS arm could control the increase of severe toxicities, which were observed frequently in patients with low renal function in patients receiving fixed dose of CS. Clinical trial information: 000007652.

scholarly journals BRAF Non-V600E Mutated Metastatic Colorectal Cancer in a Young Patient: Discussion from a Case Report

2019 ◽  
Vol 12 (2) ◽  
pp. 426-429
Author(s):  
Laure Moisset ◽  
Judith Raimbourg ◽  
Sandrine Hiret ◽  
Jonathan Dauve ◽  
Michèle Boisdron-Celle ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Case Report ◽  
Lymph Node ◽  
Metastatic Colorectal Cancer ◽  
Peritoneal Carcinomatosis ◽  
Young Patient ◽  
Clinical Features ◽  
Short Review ◽  
Tumor Control

We report the case of a 32-year-old man with a caecal adenocarcinoma with major lymph node extension and peritoneal carcinomatosis, presenting a BRAF-K601E mutation. A triplet (5FU plus oxaliplatin plus irinotecan) combination with bevacizumab achieved tumor control but the disease progressed immediately after cessation and the patient died 8 months after the diagnosis. A short review of BRAF non-V600E mutations shows that outcome and clinical features depend on the mutation.

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