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

Source: http://www.asia4safehandling.org/pdf/Managing%20Toxicities%20of%20New%20Therapi.pdf

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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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