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הוראה בנושאי טיפול תרופתי בסרטן

הוראה בנושאי טיפול תרופתי בסרטן. מאמרי מפתח, קווים מנחים וסקירות נבחרות החל משנת 2000 ערך: פרופ’ נ. חיים , מאי 2004 , עודכן-ינואר 2005 (עריכת המצגת לא הסתיימה., ראה גם רשימת מאמרים נבחרים לשלב א' באתר האיגוד) כתובת לשאלות והערות: n_haim@rambam.health.gov.il. Common Toxicity Criteria.

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הוראה בנושאי טיפול תרופתי בסרטן

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  1. הוראה בנושאי טיפול תרופתי בסרטן מאמרי מפתח, קווים מנחים וסקירות נבחרות החל משנת 2000 ערך: פרופ’ נ. חיים , מאי2004 , עודכן-ינואר 2005 (עריכת המצגת לא הסתיימה., ראה גם רשימת מאמרים נבחרים לשלב א' באתר האיגוד) כתובת לשאלות והערות: n_haim@rambam.health.gov.il

  2. Common Toxicity Criteria

  3. Common Toxicity Criteria See updated criteria (Nov. 2004): http://ctep.cancer.gov/forms/CTCAEv3.pdf

  4. Chemotherapy-induced nausea and vomiting • ESMO guidelines…. • Perugia International Conference VII, 2004…. • NK1 receptor antagonists…. • ראה מצגת "מנגנוני פעולה ועמידות של תרופות ציטוטוקסיות ו”תרופות מגינות” לגבי מנגנון פעולה של התרופות השונות.

  5. Chemotherapy-induced nausea and vomiting: ESMO & Perugia Guidelines • ESMO Minimum Clinical Recommendations , ESMO Recommendations for prophylaxis of chemotherapy-induced nausea and vomiting (NV), April 2002 • Perugia International Conference VII, 2004. see: www.mascc.org -- education & resources

  6. NK1 receptor antagonists • de Wit R et al. Addition of the oral NK1 antagonist Aprepitant to standard antiemetics provided protection against nausea and vomiting during multiple cycles of cispltin-based chemotherapy. J Clin Oncol 21: 4105-11, 2003 • Hesketh PJ et al. The oral neurokinin-1 antagonist Aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational , randomized , double-blind, placebo-controlled trial in patients receiving high-dose cisplatin-the Aprepitant Protocol 052 Study Group. J Clin Oncol 21: 4112-19, 2003 • Kris MG. Why do we need another antiemetic? Just ask. J Clin Oncol 21: 4077-80, 2003 (editorial)

  7. chemotherapy and radiotherapy protectants • ASCO guidelines for the use of mesna, dexrazoxane,and amifostine …. • ראה מצגת "מנגנוני פעולה ועמידות של תרופות ציטוטוקסיות ו”תרופות מגינות” לגבי מנגנון פעולה של התרופות השונות.... • ראה מצגת "פרמקוקינטיקה ומטבוליזם..." לגבי צורות מתן של mesna.

  8. Chemotherapy and radiotherapy protectants-ASCO Guidelines Schuchter LM et al. 2002 update of recommendations for the use of chemotherapy and radiotherapy protectants: clinical practice guidelines of the American Society of Clinical Oncology. J Clin Oncol 20: 2895-2903, 2002 : Guidelines for the use of mesna, dexrazoxane, and amifostine….

  9. GCSF & Feblile neutropenia • ASCO Guidelines (GCSF)…. • ESMO Guidelines (GCSF)…. • 2002 guidelines of the Infectious Diseases Society of America (IDSA) & Fever and Neutropenia Guidelines Panel…. • ראה גם מצגת "מנגנוני פעולה של תרופות ציטוטוקסיות ותרופות מגינות"

  10. GCSF-ASCO & ESMO Guidelines • 2000 Update of recommendations for the use of hematopoietic colony-stimulating factors: evidence-based, clinical practice guidelines. Ozer H et al. for the American Society of Clinical Oncology Growth Factor Expert Panel. J Clin Oncol 18: 3558-3585, 2000. • ESMO Minimum Clinical Recommendations: ESMO Recommendations for the application of hematopoietic growth factors (hGFs)- April 2002

  11. 2002 guidelines of the Infectious Diseases Society of America (IDSA) & Fever and Neutropenia Guidelines Panel • Hughes WT et al. Clin Infect Dis 34: 730-51, 2002

  12. Epoeitin • ASCO/ASH Guidelines…. • EORTC Guidelins….

  13. Epoeitin-ASCO & EORTC Guidelines • Rizzo JD et al. Use of Epoeitin in patients with cancer: evidence-based clinical practice guidelines of the American Society of Clinical Oncology and the American Society of Hematology. J Clin Oncol 20: 4083-4107, 2002: Guidelines for the use of epoietin in patients with chemotherapy induced anemia…. • Bokemeyer C et al. EORTC guidelines for the use of erythropoietic proteins in anemic patients with cancer. Eur J Cancer 40: 2201-16, 2004 Guidelines for the use of epoietin in anemic cancer patients….

  14. Recommended guidelines for the treatment of cancer chemotherapy-induced diarrhea • Independent panel (mortality associated with IFL… • Panel recommendations….

  15. Independent panel-mortality associated with IFL • Rothenberg ML et al. Mortality associated with irinotecan plus bolus fluorouracil/leucovorin: summary findings of an independent panel. J Clin Oncol 19: 3801-7, 2001: Guidelines suggested after a report of high mortality rate associated with the “Saltz regimen”.

  16. Recommended guidelines for the treatment of cancer chemotherapy-induced diarrhea • Benson III Al B et al. Recommended guidelines for the treatment of cancer treatment-induced diarrhea. J Clin Oncol 22: 2918-26, 2004: Guidelines of an independent panel of experts. Includes also guidelines for radiotherapy-induced diarrhea). See also previous panel recommendations(Wadler S et al. Recommended guidelines for the treatment of chemotherapy-induced diarrhea. J Clin Oncol 16: 3169-3178, 1998)

  17. Extravasation of cytotoxic agents

  18. Extravasation of cytotoxic agents • Ener RA et al. Extravasation of systemic hemato-oncological therapies. Ann Oncol 15: 858-62, 2004: …includes background and suggested guidelines.

  19. Chemotherapy sensitivity and resistance assays • ASCO assessment….

  20. Chemotherapy sensitivity and resistance assays: ASCO assessment • Schrag D et al. American Society of Clinical Oncology technology assessment: chemotherapy sensitivity and resistance assays. J Clin Oncol 22: 3631-8, 2004: “The use of chemotherapy sensitivity and resistance assays to select chemotherapeutic agents for individual patients is not recommended outside the clinical trial setting.” See also a systematic review: Samson DJ et al. J Clin Oncol 22: 3618-30, 2004: “ ….These results do not establish the relative effectiveness of assay-guided treatment and empiric treatment”.

  21. Thalidomide • Mechanism of action, side effects, current role in solid tumors….

  22. Thalidomide: Mechanism of action, side effects, current role in solid tumors • Kumar S et al. J Clin Oncol 22: 2477-88, 2004 (review) and/or: Eleutherakis-Papaiakovou V et al. Ann Oncol 15: 1151-60, 2004 (review)

  23. Somatostatin analogs • Consensus report of the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system….

  24. Somatostatin analogs • Oberg K et al. Consensus report of the use of somatostatin analogs for the management of neuroendocrine tumors of the gastroenteropancreatic system. Ann Oncol 15: 966-73, 2004 A consensus report on the use of somatostatin analogs in the management of neuroendocrine tumors of the gastroenteropancreatic system.

  25. Bisphosphonates • ASCO Guidelines….

  26. Bisphosphonates-ASCO Guidelines • Hillner BE et al. American Society of Clinical Oncology 2003 Update on the Role of Bisphosphonates and Bone Health Issues in Women With Breast Cancer. J Clin Oncol 21: 4042-57, 2003 Schedule of administration of pamidronate, and zoledronic acid; guidelines for administration in patients with renal dysfunction…. see also previous version:J Clin Oncol 18: 1378-91, 2000.

  27. Breast cancer • Dose-dense vs. conventional AC/taxol as adjuvant in node-positive breast cancer…. • ATAC…. • Extending adjuvant hormone therapy beyond tamoxifen: - Exemestane after 2 to 3 years of tamoxifen in post menopausal women…. • - Letrozole after 5 years of tamoxifen…. • Herceptin with chemotherpy and as single agent ….. • Herceptin every 3 weeks….

  28. Dose-dense vs. conventional AC/taxol as adjuvant in node-positive breast cancer • Citron ML et al. J Clin Oncol 21: 1431-39, 2003 • See also editorial: Piccart-Gebhart MJ, Mathematics and oncology: a mach for life? J Clin Oncol 21: 1425-8, 2003 (editorial) • The dose-dense arms improved DFS; severe neutropenia was less frequent in pts treated with the dose-dense regimens.

  29. ATAC study • Baum M et al. Cancer 98: 1802-10, 2003 Anastrazole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer. Results of the ATAC trial efficacy and safety update analyses.

  30. Breast cancer-Extending adjuvant hormone therapy beyond tamoxifen • Goss PE et al. N Engl J Med 349: 1793-802, 2003 As compared with placebo, letrozole after the completion of standard tamoxifen significantly improves DFS. • Coombes RC et al. N Engl J Med 350: 1081-92, 2004 Exemestane therapy after 2 to 3 years of tamoxifen significantly improved DFS as compared with the standard 5 yrs of tamoxifen.

  31. Herceptin chemotherpy and as single agent • Slamon DJ et al. N Engl J Med 344: 783-792, 2001 Herceptin increases the clinical benefit of first-line chemotherapy in MBC that overexpress HER 2. • Vogel CL et al. J Clin Oncol 20: 719-26, 2002 Single agent herceptin is active and well tolerated (objective response rate 26%; 34% in FISH positive).

  32. Herceptin every 3 weeks • Leyland-Jones B et al. J Clin Oncol 21: 3965-71, 2003 Herceptin every 3 weeks in combination with paclitaxel is generally well tolerated. Additional investigation of this schedule is warranted. See also editorial: • Cobleigh M and Frame D. J Clin Oncol 21: 3900-1, 2003

  33. Colorectal cancer • Bevacizumab (avastin) in metastatic colorectal cancer…. • Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer…. • Cetuximab & Cetuximab plus irinotecan in irinotecan-refractory MCRC…. • ASCO recommendations on adjuvant chemotherapy for stage II colon cancer….

  34. Bevacizumab (avastin) in metastatic colorectal cancer • Kabbinavar F et al. J Clin Oncol 21: 60-5, 2003 A phase II randomized study that compared 5FU/LCV to 5FU/LCV+ avastin as first-line in MCRC. “...encouraging results…” • Hurwitz H et al. N Engl J Med 350: 2335-42, 2004): Addition of avastin to standard IFL (irinotecan, 5FU, leucovorin) in MCRC improved response rate, progression free survival, and survival.

  35. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer • Andre T et al. N Engl J Med 350: 2343-51, 2004 (Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer=MOSAIC) Adding oxaliplatin to a regimen of 5FU/LCV improves the adjuvant treatment of colon cancer.

  36. Cetuximab & Cetuximab plus irinotecan in irinotecan-refractory MCRC • Cunnigham D et al. N Engl J Med 351:337-45, 2004 Cetuximab has clinically significant activity when given alone or in combination with irinotecan in pts with irinotecan-refractory CRC.

  37. ASCO recommendations on adjuvant chemotherapy for stage II colon cancer • Benson III AlB et al. J Clin Oncol 22: 3408-19, 2004

  38. Imatinib (Glivec) in GISTs • ….

  39. Imatinib (Glivec) in GISTs • Demetri GD et al. N Engl J Med 347: 472-80, 2002 54% had PR and 28% had stable disease…..no significant differences in response rate between 400 mg/day and 600 mg/day. • Verweij J et al. Lancet 25: 1127-34, 2004 5% CR, 47% PR, 32% Stable disease. 400 mg/day was similar to 800 mg/day in terms of response rate, but the higher dose produced significantly longer progression-free survival.

  40. Gynecological tumors • Randomized Intergroup trial of cisplatin-paclitaxel vs. cisplatin-cyclophosphamide in advanced epithelial ovarian cancer….

  41. Randomized Intergroup trial of cisplatin-paclitaxel vs. cisplatin-cyclophosphamide in advanced epithelial ovarian cancer • Piccart MJ et al. Randomized trial of cisplatin-paclitaxel versus cisplatin-cyclophosphamide in women with advanced epithelial ovarian cancer: three-year results. J Natl Cancer Inst 92: 699-708, 2000 The paclitaxel-containing combination was associated with better progression free survival and survival. see also GOG study: McGuire WP et al. N Engl J Med 334: 1-6, 1996

  42. Head & Neck carcinoma • Post operative irradiation with or without concomitant cisplatin for locally advanced disease….

  43. Post operative irradiation with or without concomitant cisplatin for locally advanced disease • Cooper JS et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck. N Engl J Med 350: 1937-44, 2004 • Bernier J et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer. N Engl J Med 350: 1952-42, 2004 Post operative irradiation with concomitant cisplatin for locally advanced disease is associated with improved local control and disease-free survival.

  44. Lung • Cisplatin-based adjuvant chemotherapy in pts with completely resected NSCLC…. • Gefetinib (Iressa) plus chemotherapy is not better than chemotherapy alone…. • Meta-analysis of cis-containing vs. carbo-containing in advanced NSCLC….

  45. Cisplatin-based adjuvant chemotherapy in pts with completely resected NSCLC • The International Adjuvant Lung Cancer Trial Collaborative Group. N Engl J Med 350:351-60, 2004 4 cycles of cisplatin-based chemo (+vindesine/vinblastine/vinorelbine/etoposide)-improves survival (stage I-III, who had undergone complete resection).

  46. Gefetinib (Iressa) plus chemotherapy is not better than chemotherapy alone • (Giaccone G et al. J Clin Oncol 22: 777-84, 2004) INTACT 1: addition of gefitinib to cisplatin/gemcitabine did not improve therapeutic outcome in advanced NSCLC • (Herbst RS et al. J Clin Oncol 22: 785-94, 2004) INTACT 2: addition of gefitinib to paclitaxel/carboplatin did not improve therapeutic outcome in advanced NSCLC • Baselga J. J Clin Oncol 22: 759-61, 2004 (editorial)

  47. Meta-analysis of cis-containing vs. carbo-containing in advanced NSCLC…. • Hotta K et al. J Clin Oncol 22: 3852-9, 2004 • 8 trials (2948 pts) were identified. • The combination of chemotherapy consisting of cisplatin + a new agent produced a significant survival advantage compared to that of carboplatin+ the same new agent • There was no advantage to the cisplating-containing chemotherapy in an overall analysis, that included both new agents and new agents.

  48. Lymphomas • CHOP plus rituximab in elderly pts with diffuse large-B-cell lymphoma….

  49. CHOP plus rituximab (Mabthera) in elderly pts with diffuse large-B-cell lymphoma • Coiffier B et al. N Engl J Med 346: 235-242, 2002 R-CHOP is better than CHOP in elderly pts with diffuse large-B-cell lymphoma in terms of CR rate, DFS, and OS, without a clinically significant increase in toxicity.

  50. Urological Tumors • Neoadjuvant chemo plus cystectomy vs. cystectomy alone for locally advanced bladder cancer…. • Randomized trials of docetaxel in hormone refractory prostate cancer….

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