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Managing side effects of chemotherapy in colorectal cancer

Managing side effects of chemotherapy in colorectal cancer. Dr Ian Chau Consultant Medical Oncologist The Royal Marsden Hospital London & Surrey. Common side effects. Bone marrow – red blood cells, white blood cells and platelets

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Managing side effects of chemotherapy in colorectal cancer

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  1. Managing side effects of chemotherapy in colorectal cancer Dr Ian Chau Consultant Medical Oncologist The Royal Marsden Hospital London & Surrey

  2. Common side effects • Bone marrow – red blood cells, white blood cells and platelets • Gastrointestinal – mouth ulcers, diarrhoea, nausea and vomiting • Nerve toxicity • Blood vessels – blood clots, high blood pressure • Skin rash

  3. Bone marrow • Rapid cell turnover • Short term effect - anaemia, infection, low platelets • Usually no long term sequelae • No good evidence of long term effects on immune system • Immune surveillance in colorectal cancer • Lymph node yield • Stage II vs. stage III disease

  4. Gastrointestinal tract • Usually happens within the first 2-3 cycles of chemotherapy • Female > male for diarrhoea • Again no long term sequelae

  5. p=0.164 p<0.001 p=0.039 p=0.189 Chau et al Eur J Cancer 2005

  6. P<0.001 p=0.014 p=0.034 p=0.062

  7. Nerve toxicity • Relates to oxaliplatin • Cumulative side effect • Could be long term

  8. MOSAIC nerve toxicity(n=2,246) Andre et al J Clin Oncol 2009

  9. Grading of nerve toxicity • Grade 1: mild pins and needles, loss of deep tendon reflexes • Grade 2: mild or objective sensory loss or moderate pins and needles • Grade 3: severe objective sensory loss or paresthesias that interfere with function. • No grade 4 neurosensory toxicity.

  10. MOSAIC nerve toxicity(n=2,246) Andre et al J Clin Oncol 2009

  11. Time to resolution of neurotoxicity (NSABP C-07) Land et al J Clin Oncol 2007

  12. Nerve toxicity (NSABP C-07) • At their first on-treatment assessment, 98 patients (8%) in the FULV group and 836 patients (68%) in the oxaliplatin group had neurotoxicity according to the NCI-Sanofi criteria. • Among those patients, the median time from the start of treatment to resolution of neurotoxicity was 4.8 months for FULV v 9.0 months for FLOX. • At 6 months, 36% of the FULV group versus 70% of the FLOX group had unresolved neurotoxicity. • In the FLOX group, among those whose initial assessment indicated neurotoxicity, 10% of patients still had unresolved neurotoxicity at 27.2 months.

  13. Neurotoxicity substudy (n=400)(NSABP C-07) p=0.009 p<0.0001 Mean total NTX-12 score (change from baseline)

  14. Self reported neurological symptoms at 18 months F/U “somewhat” or more severe Symptoms FULV FLOX Trouble hearing 6.5% 16.7% Ringing in ears 4% 8.6% Weak all over 6.9% 8.7% Foot discomfort 3.8% 14.2% Foot numbness/tingling 4.6% 22.1% Hand discomfort 5.4% 10.7% Hand numbness/tingling 6% 11.9% Hand/foot pain in cold 6.1% 14.9% Trouble feeling shape 1.5% 5.6% Trouble with button 1.5% 2.5% Trouble with walking 3% 6.7%

  15. Blood vessels • Side effects relate to antibody against new blood vessel formation in cancer

  16. Angiogenesis is involved throughout tumour formation, growth and metastasis Premalignant stage Malignant tumour Tumourgrowth Vascularinvasion Dormantmicrometastasis Overtmetastasis (Avascular tumour) (Angiogenicswitch) (Vascularisedtumour) (Tumour cellintravasation) (Seeding indistant organs) (Secondary angiogenesis) Stages at which angiogenesis plays a role in tumour progression Adapted from Poon RT, et al. J Clin Oncol 2001;19:1207–25

  17. VEGF and other signals promote the angiogenic switch in tumours • Larger tumour • Vascular • Metastatic potential • Small tumour (1–2mm) • Avascular • Dormant Angiogenic switch Results in overexpressionof pro-angiogenic signals,such as VEGF Adapted from Bergers G, et al. Nature 2002;3:401–10

  18. Bevacizumab mechanism of action EARLY BENEFIT CONTINUED BENEFIT Regression of existing microvasculature Inhibition of vessel regrowth and neovascularisation Normalisation of surviving microvasculature • Bevacizumab may act against tumours in three ways • regression of existing microvasculature • normalisation of mature vasculature • inhibition of production of new vasculature

  19. C-08: Adjuvant bevacizumab safety All results are non-significant Allegra et al J Clin Oncol 2009

  20. C-08: Adjuvant bevacizumab safety Allegra et al J Clin Oncol 2009

  21. C-08: Adjuvant bevacizumab safety within 12 months of finishing chemotherapy Allegra et al J Clin Oncol 2009

  22. Skin rash • Relates to either 5-FU/capecitabine or antibody against epidermal growth factor receptor (EGFR)

  23. STEPP skin care • Pre-emptive skin treatment regimen was administered beginning day −1 (one day before the administration of the first EGFR antibody dose) and continued through weeks 1 to 6, and • This consisted of • skin moisturizer applied to face, hands, feet, neck, back, and chest daily in the morning on rising; • sunscreen (PABA free, SPF ≥ 15, UVA and UVB protection) applied to exposed skin areas before going outdoors; • topical steroid (1% hydrocortisone cream) applied to face, hands, feet, neck, back, and chest at bedtime; and • doxycycline 100 mg twice per day. Lacouture et al J Clin Oncol 2010

  24. Time to first occurrence of specific grade 2 or higher skin toxicity.

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