S3534 FOLFOX Causing Fatal Cardiac Adverse Event While Managing Colorectal Cancer

Background: Pre-treated patients with first-line treatment can be offered a second treatment with the aim of improving their poor clinical prognosis. The therapy of metastatic colorectal cancer (CRC) patients who did not respond to first-line therapy has limited treatment options. Recently, many studies have paid much attention to the efficacy of bevacizumab as an adjuvant treatment for metastatic colorectal cancer. Objectives: We aimed to evaluate the efficacy and toxicity of bevacizumab plus chemotherapy compared with bevacizumab-naive based chemotherapy as second-line treatment in people with metastatic CRC. Methods: Electronic databases were searched for eligible studies updated to March 2018. Randomized-controlled trials comparing addition of bevacizumab to chemotherapy without bevacizumab in MCRC patients were included, of which, the main interesting results were the efficacy and safety profiles of the addition of bevacizumab in patients with MCRC as second-line therapy. Result: Five trials were eligible in the meta-analysis. Patients who received the combined bevacizumab and chemotherapy treatment in MCRC as second-line therapy showed a longer overall survival (OS) (OR=0.80,95%CI=0.72-0.89, P<0.0001) and progression-free survival (PFS) (OR=0.69,95%CI=0.61-0.77, P<0.00001). In addition, there was no significant difference in objective response rate (ORR) (RR=1.36,95%CI=0.82-2.24, P=0.23) or severe adverse event (SAE) (RR=1.02,95%CI=0.88-1.19, P=0.78) between bevacizumab-based chemotherapy and bevacizumabnaive based chemotherapy. Conclusion: Our results suggest that the addition of bevacizumab to the chemotherapy therapy could be an efficient and safe treatment option for patients with metastatic colorectal cancer as second-line therapy and without increasing the risk of an adverse event.

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Cytokine release syndrome in a patient with colorectal cancer after vaccination with BNT162b2

Nature Medicine ◽

10.1038/s41591-021-01387-6 ◽

2021 ◽

Author(s):

Lewis Au ◽

◽

Annika Fendler ◽

Scott T. C. Shepherd ◽

Karolina Rzeniewicz ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Checkpoint Inhibitors ◽

Temporal Association ◽

Cytokine Release ◽

Cytokine Release Syndrome ◽

Vaccination Programs ◽

Patients With Cancer ◽

Related Adverse Event ◽

Pd1 Blockade

AbstractPatients with cancer are currently prioritized in coronavirus disease 2019 (COVID-19) vaccination programs globally, which includes administration of mRNA vaccines. Cytokine release syndrome (CRS) has not been reported with mRNA vaccines and is an extremely rare immune-related adverse event of immune checkpoint inhibitors. We present a case of CRS that occurred 5 d after vaccination with BTN162b2 (tozinameran)—the Pfizer-BioNTech mRNA COVID-19 vaccine—in a patient with colorectal cancer on long-standing anti-PD-1 monotherapy. The CRS was evidenced by raised inflammatory markers, thrombocytopenia, elevated cytokine levels (IFN-γ/IL-2R/IL-18/IL-16/IL-10) and steroid responsiveness. The close temporal association of vaccination and diagnosis of CRS in this case suggests that CRS was a vaccine-related adverse event; with anti-PD1 blockade as a potential contributor. Overall, further prospective pharmacovigillence data are needed in patients with cancer, but the benefit–risk profile remains strongly in favor of COVID-19 vaccination in this population.

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Difference in Neutropenia due to Administration Schedule of TAS-102

Case Reports in Oncology ◽

10.1159/000460242 ◽

2017 ◽

Vol 10 (1) ◽

pp. 226-229 ◽

Cited By ~ 3

Author(s):

Yoichiro Yoshida ◽

Naoya Aisu ◽

Ai Mogi ◽

Akira Komono ◽

Ryohei Sakamoto ◽

...

Keyword(s):

Colorectal Cancer ◽

Bone Marrow ◽

Overall Survival ◽

Adverse Event ◽

Metastatic Colorectal Cancer ◽

Common Adverse Event ◽

Bone Marrow Suppression ◽

Effective Prevention ◽

Administration Method ◽

Prevention Method

TAS-102 significantly improves overall survival in patients with metastatic colorectal cancer. The most common adverse event of TAS-102 is bone marrow suppression, which leads to neutropenia. The incidence of neutropenia is high, and there is no known effective prevention method. Furthermore, the administration method of TAS-102 is complicated. We reported that neutropenia could be avoided by changing to a simple administration method of TAS-102.

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Preventive approach to allergic reaction to oxaliplatin

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.14569 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 14569-14569

Author(s):

M. Suenaga ◽

N. Mizunuma ◽

K. Chin ◽

Y. Kuboki ◽

E. Shizozaki ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Allergic Reaction ◽

Cancer Patients ◽

Treatment Time ◽

Significant Delay ◽

Preventive Approach ◽

Group A ◽

Group B ◽

Financial Relationships

14569 Background: Allergic reaction to oxaliplatin is a chronic adverse event in the treatment of cancer. Patients with colorectal cancer were given FOLFOX4, using preventive approaches composed of two steps. Methods: Step I included 40 mg famotidine, 8 mg dexamethasone from the first cycle and 50 mg of diphenhydramine after cycle 4. In step II, for the patients who had a reaction but not a severe one in step I, a 20 mg dose of dexamethasone and four-hour oxaliplatin infusion were administered. Results: Forty-eight patients (15.1%) presented with allergic reaction, divided into group A receiving step I except diphenhydramine and B undergoing all of step I. Significant delay on occurrence was observed in group B. Thirty patients underwent step II. Prevention success (well-prevented) was defined as no reaction in two or more treatments. Allergic reaction appeared again in eleven patients (not well-prevented, 36.7%), but most well-prevented patients got four months longer treatment time with no reaction than not well-prevented patients. Conclusions: In our preventive approach, administration of H-1RA was effective in delaying the occurrence of allergic reaction to oxaliplatin, and increased dose of dexamethasone 20 mg and prolongation of oxaliplatin infusion from 2 to 4 hours was succeeded in continuing the FOLFOX4. No significant financial relationships to disclose.

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Evaluation of reported bone pain in patients (pts) receiving chemotherapy in pegfilgrastim clinical trials

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.9621 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 9621-9621 ◽

Cited By ~ 1

Author(s):

J. Sierra ◽

R. Harms ◽

M. Mo ◽

C. L. Vogel

Keyword(s):

Colorectal Cancer ◽

Clinical Trials ◽

Adverse Event ◽

Growth Factors ◽

Surface Area ◽

Body Surface Area ◽

Body Surface ◽

Bone Pain ◽

The Mean ◽

Grade 3

9621 Background: Bone pain is the most commonly reported treatment-related adverse event (AE) associated with colony-stimulating growth factors. Some authors have suggested that pegfilgrastim-induced bone pain is unpredictable and refractory to analgesics (Kirshner 2007), though that impression may not be uniformly accepted. To better characterize this adverse event we evaluated bone pain across pegfilgrastim clinical trials. Methods: Completed Amgen-sponsored trials that both incorporated pegfilgrastim 6mg administered 24 hours after chemotherapy and utilized MedDRA library coding of AEs were examined. Included were 2 studies comparing pegfilgrastim with placebo (Vogel 2005, Hecht 2007) and 2 studies comparing pegfilgrastim with filgrastim (Sierra 2008, Lopez 2004). The incidence of bone pain was determined by treatment (pegfilgrastim, filgrastim, or placebo), chemotherapy (taxane-containing or not), cycle, severity, age, and body surface area (BSA). Analysis and recoding of studies with preferred AEs coded to nonMedDRA dictionaries is ongoing. Results: 1310 pts (filgrastim=67, pegfilgrastim=665, placebo=578) were analyzed. In studies comparing pegfilgrastim (n=74) and filgrastim (n==7) in pts with AML and NHL, 52% were female, and the mean (SD) age was 50 (15.1) years. Similar proportions (CI) of pts reported bone pain (24.3% [16.1, 35.7] vs 25.4% [15.5, 37.5], respectively), and grade 3/4 bone pain was reported in 3% [0.3, 9] versus 0% [-, -] of pts, respectively. Studies comparing pegfilgrastim (n=591) and placebo (n=578) pts in breast and colorectal cancer are below ( Table ). Conclusions: Bone pain of any grade was commonly reported in all 3 groups (pegfilgrastim, filgrastim, and placebo) and was marginally higher in pts receiving pegfilgrastim compared with placebo. Bone pain was most common in cycle 1. Severe bone pain was infrequently reported. Bone pain was similar in pts receiving pegfilgrastim and filgrastim. Chemotherapy (eg, taxanes) may also contribute to bone pain. [Table: see text] [Table: see text]

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Cost-effectiveness of regorafenib for pretreated metastatic colorectal cancer patients in the United States.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.4_suppl.578 ◽

2013 ◽

Vol 31 (4_suppl) ◽

pp. 578-578 ◽

Cited By ~ 1

Author(s):

Brian S. Seal ◽

Ipek Özer-Stillman ◽

John Whalen ◽

Apoorva Ambavane ◽

Avin Yaldo ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Cost Effectiveness ◽

Metastatic Colorectal Cancer ◽

Unmet Need ◽

Drug Acquisition ◽

Trial Data ◽

Administrative Claims ◽

Heavily Pretreated ◽

The Cost

578 Background: There is an unmet need for treatments that provide a survival benefit for patients with heavily pretreated metastatic colorectal cancer (mCRC). In a randomized, double-blind, placebo-controlled trial, patients treated with regorafenib plus best supportive care (BSC) had significant improvement in overall survival (OS) versus patients in the placebo arm receiving BSC alone. The aim of this study was to estimate the cost-effectiveness of regorafenib for the treatment of patients with mCRC after failure or intolerance to irinotecan-, oxaliplatin-, and fluorouracil-based regimens, from the perspective of a U.S. health care payer. Methods: A cohort-partition model was developed to simulate treatment costs and survival for patients treated with regorafenib or BSC alone. Survival was projected by fitting Weibull distributions to trial data. Mean duration of treatment (3.0 months regorafenib, 2.1 months BSC), utilities (0.71 on treatment, 0.59 post-treatment) and serious adverse event rates were also based on trial data. Monthly drug monitoring and physician fee costs were based on Medicare fee schedules. Routine mCRC care and adverse event unit costs were obtained from an analysis of administrative claims in two large managed care databases. Costs were estimated in 2012 USD. Results: Patients treated with regorafenib had prolonged survival versus BSC alone (0.75 versus 0.60 years) and also had higher lifetime costs ($97,700 versus $59,494). The improvement in quality-adjusted life years (0.47 versus 0.37) was small due to the heavily pretreated nature of the patient population. The increase in costs was attributable to increases in costs for drug acquisition, adverse events , and routine care from increased survival. Conclusions: Regorafenib increases life expectancy for patients with pretreated metastatic colorectal cancer. The cost of this benefit could be considered high; however, it could be justifiable given high unmet need for these patients. The increase in cost is primarily due to drug acquisition costs, similar to other recent treatments for metastatic cancers.

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Effects of the leucovorin shortage: Pilot study investigating cost, efficacy, and toxicity comparison of low fixed-dose versus body surface area-adjusted leucovorin dosing in patients with resectable colon or metastatic colorectal cancer

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155215624262 ◽

2016 ◽

Vol 23 (3) ◽

pp. 163-172 ◽

Cited By ~ 2

Author(s):

Brandon R Shank ◽

Amy H Seung ◽

Katharine Kinsman ◽

Matthew J Newman ◽

Ross C Donehower ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Pilot Study ◽

Metastatic Colorectal Cancer ◽

Small Sample Size ◽

Small Sample ◽

Disease Stage ◽

Fixed Dose ◽

Dosing Strategies ◽

Event Rates

Purpose As a result of the leucovorin shortage, we switched from BSA-adjusted to low fixed-dose leucovorin in patients with colon cancer receiving fluorouracil-containing therapy. Methods A retrospective, pilot study of adults receiving intravenous leucovorin as part of a fluorouracil-containing treatment was conducted including individuals with stage II or III colon or newly diagnosed metastatic colorectal cancer. One low fixed-dose (leucovorin 50 mg) patient was matched by the investigator to one BSA-adjusted (leucovorin 200–500 mg/m2/dose) patient on disease stage and age. The objectives were to compare cost of alternative dosing strategies as well as efficacy and adverse event rates. Only patients being treated in the first-line metastatic colorectal cancer setting were included in the efficacy analysis. Results Fifty-eight patients were included. Leucovorin cost was reduced by 7- to 14-fold, and we were able to conserve a total of 1580–3400 doses of leucovorin by changing to fixed-dose (estimated from 200 mg/m2 or 400 mg/m2 dosing strategies, respectively). No statistically significant differences in progression-free survival ( p = 0.254), overall survival ( p = 0.923), or complications resulted. Conclusion Our decision to reduce the dose of leucovorin allowed us to conserve supply and control cost. The small sample size did not allow us to detect differences in efficacy or adverse event rates, and thus a larger study would be required to confirm our findings that efficacy was not compromised nor adverse effects greater.

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Capecitabine-Associated Terminal Ileitis

Case Reports in Oncology ◽

10.1159/000492781 ◽

2018 ◽

Vol 11 (3) ◽

pp. 654-659 ◽

Cited By ~ 5

Author(s):

Irene E.G. van Hellemond ◽

Annemarie M. Thijs ◽

Geert-Jan Creemers

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Side Effect ◽

Palliative Chemotherapy ◽

Terminal Ileitis ◽

Oral Fluoropyrimidine

Capecitabine is an oral fluoropyrimidine used as adjuvant and palliative chemotherapy in patients with colorectal cancer. Diarrhea is a well-known side effect of capecitabine and 5-fluorouracil agents. We present a case with terminal ileitis as a rare adverse event of capecitabine treatment. Capecitabine-induced terminal ileitis is likely to be underreported. It should be considered more often as a cause of severe and atypical complaints of diarrhea during treatment with capecitabine or other 5-fluorouracil agents.

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Oxaliplatin-Induced Leukocytoclastic Vasculitis under Adjuvant Chemotherapy for Colorectal Cancer: Two Cases of a Rare Adverse Event

Case Reports in Oncology ◽

10.1159/000357166 ◽

2013 ◽

Vol 6 (3) ◽

pp. 609-615 ◽

Cited By ~ 6

Author(s):

Henriette Quack ◽

Luise Erpenbeck ◽

Hendrik A. Wolff ◽

Thilo Sprenger ◽

Cornelia S. Seitz ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Adjuvant Chemotherapy ◽

Leukocytoclastic Vasculitis

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Panitumumab-Associated Drug-Induced Immune Thrombocytopenia in a Patient with Colorectal Cancer

Case Reports in Oncology ◽

10.1159/000512821 ◽

2021 ◽

pp. 85-89

Author(s):

Shigemasa Takamizawa ◽

Hirokazu Shoji ◽

Hidekazu Hirano ◽

Koji Izutsu ◽

Shun Yamamoto ◽

...

Keyword(s):

Colorectal Cancer ◽

Adverse Event ◽

Platelet Count ◽

Drug Treatment ◽

Metastatic Colorectal Cancer ◽

Clinical Diagnosis ◽

Immune Thrombocytopenia ◽

Severe Thrombocytopenia ◽

Suspected Drug ◽

Drug Induced

Severe thrombocytopenia is a rare adverse event of panitumumab. Here, we report the first patient with metastatic colorectal cancer who developed severe thrombocytopenia, diagnosed as panitumumab-associated drug-induced immune thrombocytopenia (DITP). A clinical diagnosis of DITP can be obtained by excluding other causes of thrombocytopenia and is confirmed by the recovery of thrombocytopenia after the discontinuation of the suspected drug. Treatment includes permanent discontinuation of the suspected drug. Re-exposure should be avoided. It should be kept in mind that panitumumab can induce DITP in the case of a new, sudden, unexpected, and isolated drop in platelet count after excluding other causes of thrombocytopenia.

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