Patient 1 - Case of acute coronary syndrome associated with continuous intravenous 5-fluorouracil (5-FU) infusion²:
 

Patient Characteristics

• 55 years old 
• Female
• Non-smoker  

Clinical History

• Presented with colonic obstructive symptoms and anaemia – diagnosed with an adenocarcinoma of the sigmoid 
• Urgent left hemicolectomy showed a moderately differentiated adenocarcinoma that perforated the visceral peritoneum, had disseminated to fifteen regional lymph nodes and there were several metastatic hepatic nodules
• No history of previous coronary artery disease, congestive heart failure, diabetes mellitus, hypercholesterolaemia or hypertension
• No family history of heart disease
• ECHO and ECG showed no alterations
• History of limb thrombosis, managed with warfarin* treatment

Chemotherapy Treatment Regimen 

• Palliative chemotherapy with mFOLFOX6 regimen – folinic acid 400mg/m² plus oxaliplatin 85mg/m², IV in 2 hours plus 5-FU 400mg/m² in bolus plus 5-FU 2400 mg/m², IV continuous infusion in 46 hours

Current Presentation 

• Retrosternal burning pain
• Abnormal ECG
• Mild elevations of cardiac enzymes
• Increased INR
• ECHO showed global left hypokinesis

Outcome: Acute coronary syndrome probably secondary to arterial vasospasm associated with continuous intravenous 5-FU infusion
 

Could this CRC patient be a candidate for TOMUDEX? 
 

Note: Leucovorin (folinic acid), folic acid or vitamin preparations containing these agents must not be given immediately prior to or during administration of raltitrexed, since they may interfere with its action.

Patient 2 - Case of 5-FU induced cardiotoxicity in a patient with coronary artery disease³:
 

Patient Characteristics

• 62 years old 
• Male

Clinical History  

• Presented with unresectable liver metastases of a sigmoid adenocarcinoma  
• History of coronary artery disease with two myocardial infractions 14 and 22 years ago, received coronary bypass grafts to the left anterior descending artery (LAD) and the left circumflex artery (LCX) 12 years prior. 
• Taking a long acting nitrate and aspirin**. 
• ECG shows signs of myocardial scar but otherwise normal.

Chemotherapy Treatment Regimen 

• Weekly treatment with folinic acid 500mg/m² given as a 2-hour infusion followed by 5-FU 2600mg/m² as a 24h infusion

Current Presentation 

• Retrosternal chest pain
• ECG showing non-specific ST segment elevation in anterior leads and T-wave inversion in lead III
• Serial serum cardiac enzyme measurements unchanged
• Coronary angiography demonstrates severe stenosis of LAD bypass graft and a moderate stenosis of LCX bypass graft

Outcome: 5-FU induced cardiotoxicity and ischaemic heart disease.

Could this CRC patient be a candidate for TOMUDEX?
 

Note: Leucovorin (folinic acid), folic acid or vitamin preparations containing these agents must not be given immediately prior to or during administration of raltitrexed, since they may interfere with its action.

Abbreviations:
 

5-FU, 5-fluorouracil; CRC, colorectal cancer; ECG, electrocardiogram; ECHO, echocardiogram; LAD, left anterior descending artery; LCX, left circumflex artery; INR, international normalised ratio; IV, intravenous; mFOLFOX6, modified FOLFOX-6 regimen 

Footnotes:

*Raltitrexed is 93% protein bound and while it has the potential to interact with similarly highly protein bound drugs, no displacement interaction with warfarin has been observed in vitro. However, a review of the clinical trial safety database did not reveal evidence of clinically significant interaction in patients treated with raltitrexed who also received concomitant warfarin.

**Data suggest that active tubular secretion may contribute to the renal excretion of raltitrexed, indicating a potential interaction with other actively secreted drugs such as non-steroidal anti-inflammatory drugs (NSAIDS). However, a review of the clinical trial safety database did not reveal evidence of clinically significant interaction in patients treated with raltitrexed who also received concomitant NSAIDS.

References:

1. TOMUDEX^® Summary of Product Characteristics.
2. Paiva CE et al. J Gastrointest Canc 2009; 40:133-137.
3. Kohne C-H, Thuss-Patience P et al. British J Cancer 1998; 77:6:973-977.