PA30326 Workshop Colorectal

Question 1

Mr CC, a 63 yr old male, presented to his GP with a 1 month history of episodes of alternating diarrhoea & constipation and intermittent episodes of blood in his stool. He is overweight, smokes 20 cigarettes a day and works in an office. When questioned on his diet, he admits that since his wife died 3 years ago, he mainly eats ready meals and takeaways. He has no history of bowel problems and no significant family history.

What risk factors does Mr CC have for developing colorectal cancer?

Answer 1

• Overweight
• Smoker
• Inactive lifestyle
• High fat diet, high calorie intake
• Low intake of fruit & veg

Question 2

Mr CC’s GP has a high suspicion that he may have bowel cancer, and sends him for an urgent colonoscopy at the hospital gastroenterology outpatients.

The colonoscopy confirmed the presence of a mass in the left side of Mr CC’s colon (sigmoid colon). A biopsy was taken which showed that this was an adenocarcinoma. A CT scan of his chest, abdomen & pelvis showed no metastatic spread. He was admitted to hospital 1 week later and underwent a sigmoid colectomy. Histology of the tumour showed that it was a Duke’s C cancer, had penetrated into the bowel wall and 4 out of 16 lymph nodes were affected. Postoperatively he made a good recovery and was discharged from hospital 10 days later.

Is Mr CC a candidate for adjuvant chemotherapy?

Answer 2

Yes, Duke’s C

- has spread to lymph nodes therefore good benefit from chemo

Question 3

Mr CC was referred by the surgical team to the oncologists, and he attended an outpatient oncology appointment where adjuvant chemotherapy was discussed. He was offered 3 choices:
FOLFOX chemotherapy
XELOX chemotherapy
Capecitabine chemotherapy

Mr CC opts for FOLFOX chemotherapy (12 cycles at 2-weekly intervals). A PICC (peripherally inserted central catheter) line is inserted 2 weeks later in preparation for him to receive this chemotherapy.

Why is folinic acid administered in this regimen?

Answer 3

• Increases & prolongs inhibition of thymidylate synthase which improves clinical outcome
• Fluorouracil inhibits thymidylate synthase to prevent synthesis of thymidine, which is a nucleoside required for DNA replication

Question 4

If Mr CC had moderately impaired renal function (GFR 40ml/min) would you need to make any modifications to drug dosages? If so, what?

Answer 4

Reduce oxaliplatin dose by 50%

Question 5

What side effects of this chemotherapy regimen should Mr CC be counselled on?

Answer 5

• Peripheral neuropathy
• Laryngo-pharyngeal dysaesthesia
• N & V
• Stomatitis
• Consipation/diarrhoea
• Mild alopecia
• Hand-foot syndorme
• Bone marrow suppression
• Line thrombus

Question 6

After the 1st cycle of FOLFOX, Mr CC suffers Grade I diarrhoea (an increase of 2-3 stools per day compared to pre-treatment).

What action should be taken by the prescribe for cycle 2?

Answer 6

Prescribe Loperamide or Codeine phosphate

Question 7

Mr CC completes 12 cycles of treatment and is discharged from oncology. He has surgical follow-up which involves a yearly colonoscopy to check for recurrent disease. Sadly, 2 years after his initial diagnosis, he presents to his GP with weight loss and fatigue, and a CT scan shows multiple liver metastases. He is referred back to oncology for consideration for further treatment.
The oncologist discusses capecitabine chemotherapy with Mr CC and it is decided to give 6 cycles of this to try to shrink the metastases. He is referred to the pharmacist prescribing clinic.

You are the pharmacist prescriber. Prescribe the first cycle of capecitabine for Mr CC, given the following information:

Answer 7

• Capecitabine dose 2300mg bd

BSA = (weight(kg) x height (cm)) / 3600 and square route it

Question 8

What are the main side effects of capecitabine?

Answer 8

• Nausea & vomitting
• Diarrhoea
• Hand-foot syndrome
• Stomatitis
• Bone marrow suppression (anaemia, neutropenia, thrombocytopenia)

Question 9

After the 3rd cycle of capecitabine, Mr CC is suffering from hand-foot syndrome (also known as palmar plantar erythrodysaesthesia – PPE). He has sore skin on his hands and blisters on his feet, and is finding it difficult to perform “fiddly” tasks such as doing up buttons as it is painful. He describes numbness in his fingertips.

What dose modification should be made (if any) by the pharmacist prescriber?

Answer 9

• Delay next cycle until toxicity resolved to grade 0-1

( skin changes without pain) then give 75% dose for next cycle

Question 10

Are there any drug interactions which may be important with capecitabine?

Answer 10

Folinates

• Avoid concomitant use of folinic acid and folic acid
• enhanced toxicity of fluroruracil

Co-trimoxazole/trimethoprim

• avoid if possible
• enhances antifolate effect

Warfarin/coumarin anticoag
- avoid use due to elevations in INR

Antacids
- produce an increase in plasma conc of capecitabine

Question 11

Why is folinic acid not needed with capecitabine?

Answer 11

Folinic acid is given with bolus fluorouracil doses to help prolong the inhibition
of thymidylate synthase, as fluorouracil has a short half life of 10 mins.  With
prolonged exposure (e.g. by giving fluorouracil by continuous infusion or by
giving capecitabine) we don’t need the folinic acid because there is enough
drug constantly present to inhibit thymidylate synthase for a long enough time to
have a therapeutic effect.