1. Infusion Reactions COLORECTAL CANCER

2.  Albert, 83M  Retired fashion designer and entrepreneur  Presented to Cabrini Brighton for C6 chemotherapy  Metastatic CRC with liver met  FOLFOX6 regimen with good effect INTRODUCTION

3.  Nov 2014  U/S and CT-CAP revealed extensive metastatic disease involving entire liver  Suspected to be secondary to a previously resected sigmoid polyps  Initial presentation  Persistent nausea, anorexia and generalised weakness  Bowel symptoms of constipation  Weight loss 5kg  Denied symptoms of liver disease  Deranged LFT HOPC

4.  Hx of colonic polyps  Routine colonoscopy for many years  Dec 2012  Polypectomy with histopathology revealing adenocarcinoma  Follow-up CT showed no evidence of nodal or distant metastasis  Follow-up colonoscopy all clear HOPC

5.  Referral to A/Prof. Gary Richardson  Work-up  PET scan – bowel and liver involvement  Tumour markers – CEA and CA19-9  Liver core biopsy – moderately differentiated adenocarcinoma  Colonoscopy + biopsy – recurrent adenocarcinoma  CRC grade IVA HOPC

6.  FOLFOX6 regimen  Oxaliplatin, Leucovorin, 5FU, Bevacizumab  Serum CEA  LFTs  Side effects  Fatigue – exercise tolerance and sleep  Bowel symptoms  GORD  Infusion reaction  Weight stable  Hypertension well controlled  Nil other significant chemo toxicity CHEMOTHERAPY

7.  Ongoing issues  Hyperlipidaemia – on Lipitor  IHD and hypertension – on Coversyl and Tenormin  Inactive issues  Gout – on prophylactic allopurinol  AF – asymptomatic since 1999  Meningioma – excised in 1997  NKDA PAST MEDICAL HISTORY

8.  Lives at home with wife  Breast cancer  Previously IADL  Golfed twice weekly, walked 18 holes  Cleaner fortnightly  Currently more fatigable  Golf once a week, requires buggy  Still gardens  One daughter  Lives nearby and helps SOCIAL HISTORY

9.  Albert 83M  Currently C6 of FOLFOX6 regimen for metastatic CRC with liver met  Has been progressing well on treatment with decline in serum CEA and improvement in LFTs  Has had relatively minor side effects from chemo  But most recently had an infusion reaction that settled with anti- histamines, and since have had oxaliplatin removed from regimen SUMMARY

10. 1.Metastatic CRC with liver met  Chemotherapy and post-chemo management 2.Medical management of IHD 3.Decline in function and exercise tolerance  EP and OT assessment 4.Social issues  Age  Assistance with ADL ISSUES

11. INFUSION REACTION

12.  Definition  An unexpected reaction that cannot be explained by the known toxicity profile of the drug  Virtually all chemotherapeutic agents have the potential to initiate an infusion reaction INFUSION REACTION

13.  Standard Infusion Reactions (SIRS)  Cutaneous  Flushing, itching, urticaria ± angioedema  Respiratory  Cough, nasal congestion, SOB, chest tightness, wheeze, hypoxia  Cardiovascular  Dizziness or syncope, tachycardia, hypotension, hypertension  Gastrointestinal  N/V, abdo pain and diarrhoea  Neuromuscular  Sense of impending doom, tunnel vision, dizziness, seizures, severe back/chest/pelvic pain  Anaphylaxis if more severe SIGNS AND SYPMTOMS

14.  Usually occurs during or within a few hours of drug infusion  Occasionally one to two days after administration  Infusion reactions found to be more common in these settings  IV administration  After multiple cycles of certain agents  Prior infusion reactions to drug of same chemical class  History of multiple drug allergies TIMING AND RISK FACTORS

15.  Taxanes  Platinum  Doxorubicin  L-asparaginase  Procarbazine  Etoposide  Bleomycin  Cytarabine  Ixabepilone COMMONLY IMPLICATED AGENTS

16. GRADE

17.  Immediate  Symptomatic management ± resuscitation  Rechallenge  Reduced infusion rate  Premedication  Desensitisation techniques MANAGEMENT OF SIR

18.  Classic type 1 IgE-mediated allergic reaction  Characterised by  Pruritus, urticaria, bronchospasm, facial swelling and hypotension  Abdominal pain, nausea, vomiting and diarrhoea are also relatively common in platinum drug-induced anaphylaxis  One study of 272 patients receiving oxaliplatin found 48 (18%)patients who developed infusion reaction despite prevention regimen of famotidine and dexamethasone 3  Another study suggested benefit from higher doses of dexamethasone in conjunction with H1 and H2 receptor blockers (7% vs. 20% reaction rate) OXALIPLATIN AND PLATINUM DRUGS