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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 אוקטובר 2005 המצגת אינה מעודכנת כתובת לשאלות והערות: n_haim@rambam.health.gov.il. CTCAE [formerly known as CTC (CommonToxicity 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 אוקטובר 2005 המצגת אינה מעודכנת כתובת לשאלות והערות: n_haim@rambam.health.gov.il

  2. CTCAE [formerly known as CTC (CommonToxicity Criteria)]…..

  3. CTCAE [formerly known as CTC (Common Toxicity Criteria Common Toxicity Criteria)] • http://ctep.cancer.gov …..CTCAE (formerly known as CTC) v2.0 and v3.0 (v3.0 – publish date: December 12, 2003)

  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. Brain Tumors • Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma….

  28. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma • Stupp R et al. N Engl J Med 352: 987-96, 2005: The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in clinically meaningful and statistically significant survival benefit with minimal additional toxicity.

  29. Breast cancer • Dose-dense vs. conventional AC/taxol as adjuvant in node-positive breast cancer…. • ATAC…. • adjuvant hormone therapy beyond tamoxifen: - Exemestane after 2 to 3 years of tamoxifen in post menopausal women…. - Anastrazole after 2-3 yrs of tamoxifen…. • - Letrozole after 5 years of tamoxifen…. • Herceptin with chemotherpy and as single agent ….. • Herceptin every 3 weeks…. • Herceptin as adjuvant…. • ASCO technology assessment of the use of aromatase inhibitors….

  30. 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.

  31. ATAC study • Atac Trialists’ Group. Results of the ATAC (arimidex, tamoxifen, alone or in combination) trial after completion of 5 years’ adjuvant treatment for breast cancer. Lancet December 8, 2004

  32. 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. • Boccardo F et al. J Clin Oncol 22: 5138-47, 2005 Anastrazole after 2 to 3 years of tamoxifen significantly improved DFS as compared with the standard 5 yrs of tamoxifen (see also editorial: Pritchard KI. J Clin Oncol 22: 4850-2, 2005)

  33. 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).

  34. 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

  35. Herceptin as adjuvant therapy • Piccart-Gebhart M et al. N Engl J Med 353: 1659-72, 2005 (HERA): (Herceptin every 3 wks was given for one or two years after locoregional therapy). • Romond EH et al. N Engl J Med 353: 1673-84, 2005 (NSABP& NCCTG): (Herceptin weekly for one year initiated after AC+ paclitaxel adjuvant therapy or concomitantly with paclitaxel).

  36. ASCO technology assessment of the use of aromatase inhibitors…. • Winer EP, Hudis C, Burstein HJ et al. American Society of Clinical Oncology technology assessment of the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol 23: 619-29, 2005

  37. 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…. • Capecitabine as adjuvant in stage III (X-ACT)….

  38. 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. • Kabbinavar FF et al. J Clin Oncol 23: June 1, 2005: The addition of bevacituzumab to FU/LV provides a statistically significant and clinically relevant benefit in pts with previously untreated CRC.

  39. 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.

  40. 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.

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

  42. Capecitabine as adjuvant in stage III (X-ACT) • Twelves C et al. N Engl J Med 352: 2696-2704, 2005 Capecitabine is at least equivalent to the Mayo Clinic regimen (better DFS & less toxicity.

  43. Germ cell tumors • Radiotherapy vs single-dose carboplatin in adjuvant treatment of stage I seminoma….

  44. Radiotherapy vs single-dose carboplatin in adjuvant treatment of stage I seminoma • Oliver RT et al. Lancet 366: 293-300, 2005 A randomized study that showed non-inferiority of carboplatin to radiotherapy in the treatment of stage I seminoma.

  45. Imatinib (Glivec) in GISTs • ….

  46. 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.

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

  48. 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

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

  50. 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.

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