Robbie_plenary lecture 6- managing toxicities of new therapi
Fluorouracil 400mg/m2 bolus then 600mg/m2over 22 Hours d1, d2
– Study (Mayo Regimen x 6 Cycles vs Xeloda)
• Oxaliplatin infusion begun. 90 minutes
breathing sensation, tingling in throat.
• Increase Infusion Duration (2-6 Hours)
– Delayed Cumulative Sensory Neuropathy
• Comparable to Cisplatin• Impaired Sensation
• Related to Cumulative Dose (800mg/m2)• Usually Reversible (75% Patients)
– Worsening Neuropathy existing between
– Pharyngolaryngeal Dysesthesias with Cold
Clin Cancer Res 2004; 10: 4055-4061J Clin Oncol 2002; 16: 3478-83J Clin Oncol 2002; 15: 3359-61
• Similar Reaction, Less Intense• Cycle 11 Premedication ?
J Invest Allergol Clin Immunol 2005; 15: 75-7
• Three Cycles of Irinotecan Single Agent
– Desensitisation Protocols in Literature
Gamelin et al. Semin Oncol 2002; 29: 21-33
• Follicular Mixed Small and Large Cell
• Course 2 – 12 Months Later - (375mg/m2 x 4)
• Treated with additional 100mg Hydrocortisone
• 100mg Hydrocortisone IV, Salbutamol 5mg,
• Infusion recommenced 45 minutes later
• Recommenced 45 minutes later with no
• Dexamethasone 20mg the night before treatment
• Hydrocortisone 200mg
– “Flushed, coughing, shortness of breath”
• 100mg Hydrocortisone IV, Salbutamol 5mg,
• Recommenced 1 hour later with no further
• 67 Patients Involved (Total of 163 Infusions)
• Dexamethasone 20mg the night before and
morning of treatment
• Paracetamol 1 gram• Promethazine 12.5mg
• 4 Patients Reacted During First Cycle, but
• 5 Patients, Treated Without Steroids,
– No Problems Encountered During Infusion!
Sehn et al. Blood 2004; 104: 1407 (ASH Meeting Abstract)
– Given According to Product Information
• Reduces Microvascular Growth• Inhibits Metastasis
Sehn et al. Blood 2004; 104: 1407 (ASH Meeting Abstract)
Kabbinavar et al. J Clin Oncol 2003; 21: 60-65
• Commences Tx with Avastin® / Placebo
• Shortness of breath, Flushed, Febrile
administered, Promethazine 12.5mgLorazepam 1mg sublingual
– Lorazepam 1mg s/l plus Cetirizine 10mg o
• No Further Problems• Develops HFS on Capecitabine• Pyridoxine Disallowed on Study
Gilbar P J Oncol Pharm Pract 2003; 9: 137-150
Mortimor et al. J Oncol Pharm Pract 2003; 9: 161-166
• Udderly Smooth® Udder Cream• Aloe Vera Gel• Hydrocortisone Cream• Prednisolone Tablets• Eucerin ® Moisturising Lotion• Corn Huskers ® Lotion
• CT confirmed diagnosis in August 2001
– Married with 4 Children– Heavy Alcohol and Tobacco Use
– 2-3 Month Hx Epigastric Pain– HP Eradication Followed by Ultrasound– Multiple Liver Lesions– No Dysphagia, No Change in Bowel Habits– No Cough, No Haemoptysis
• Immediately Before Starting Cetuximab
– Able to do small jobs around the house
2 IRN 18/2/02 3 OXL 22/7/02 4 FU 3/2/03 5 MMC 12/5/03 6 SAL 14/10/03
– Wife Felt his Condition was Worsening
– 400mg/m2 Loading, then 250mg/m2 Weekly
– Vesicular, Covers 50% of the Body, Grade 3
– Rash Resolves to Grade 2– Patient Concerned About Appearance– Depressed, Not Leaving the Home
2 IRN 18/2/02 3 OXL 22/7/02 4 FU 3/2/03 5 MMC 12/5/03
– Rash Improving, Attributed to Antibiotic
6 SAL 14/10/03
– Persistent During Course of Treatment
– Appeared to “Improve” when CEA Began
Secretary U.S. Securities and Exchange Commission 100 F Street, NE Washington, D.C. 20549-9303 Comments on Proposed Acceptance from Foreign Private Issuers of Financial Statements Prepared in accordance with International Financial Reporting Standards without Reconciliation to U.S. GAAP; File No. S7-13-07 We are submitting this letter in support of the comments of several European organizatio
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