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Phase II Study of Temozolomide      and Thalidomide in   Patients With Metastatic   Neuroendocrine Tumors       J Clin Onc...
Outline   Classification and grading of NET   Introduction to temozolomide   Inclusion and exclusion criteria   Regime...
Pancreas 2010;39: 707 - 712)
Pancreas 2010;39: 707 - 712)
Endocr Relat Cancer. 2004 Mar;11(1):1-18.
Endocr Relat Cancer. 2004 Mar;11(1):1-18.
Outline   Classification and grading of NET   Introduction to temozolomide   Inclusion and exclusion criteria   Regime...
Cancer Chemother Pharmacol(2009) 64:647–655
Cancer Chemother Pharmacol(2009) 64:647–655
J Clin Oncol 25:4127-4136
Temozolomide dosing regimens for       malignant gliomas                        J Clin Oncol                        25:412...
The Oncologist 2007;12:1114–1123
The Oncologist 2007;12:1114–1123
Outline   Classification and grading of NET   Introduction to temozolomide   Inclusion and exclusion criteria   Regime...
Inclusion (1)   Histologically confirmed, locally unresectable or metastatic    neuroendocrine tumors   Prior treatment ...
Inclusion (2)   Adequate hepatic function (total and direct bilirubin < 2 *    the ULN)   ALT and AST < 5 * the ULN, and...
Exclusion   Clinically apparent CNS metastases or carcinomatous    meningitis   History of myocardial infarction 6 month...
Outline   Classification and grading of NET   Introduction to temozolomide   Inclusion and exclusion criteria   Regime...
Treatment Program   Temozolomide       150 mg/m2 days 1 to 7 and days 15 to 21   Thalidomide       daily       starti...
Temozolomide adjustment   Hold if        ANC less than 1,000/mm3        Plt less than 50,000/mm3        all nonhematol...
Thalidomide adjustment   Increased weekly by 100 mg until a maximum dose of 400    mg   Before escalation       Toxicit...
Outline   Classification and grading of NET   Introduction to temozolomide   Inclusion and exclusion criteria   Regime...
Response assessment   Every 8 weeks after initiation of treatment   Computed tomography scan   Pt with complete [CR] or...
Response assessment   PR       decrease of more than 30% in the sum of the largest        perpendicular diameters of all...
Response assessment   Stable disease:       Neither PR, nor progressive disease   Biochemical response       secondary...
Outline   Classification and grading of NET   Introduction to temozolomide   Inclusion and exclusion criteria   Regime...
Duration of Treatment   29 patients received treatment for a median of 7.3 months    (range, 1 to 23 months)   1 patient...
Treatment-related toxicities resulting in discontinuation:neuropathy (11 patients,38%, 6 pts persist > 3 wks), infection(f...
Median time to treatmentdiscontinuation for toxicity :8.4months (range, 1.5 to 7.5 months)
Median duration of response was 13.5months (range, 2 to 31 months)
Progression-free survival  Overall survival  1-year survival rate:  79% 2-year survival  rate: 61%
Outline   Classification and grading of NET   Introduction to temozolomide   Inclusion and exclusion criteria   Regime...
Discussion   Overall objective radiologic response rate of    25%(CR+PR)   Biochemical response rate of 40%   2-year su...
   Carcinoid tumor       Objective response rates of streptozocin-based        regimens: 16% to 33%                     ...
CR+PR   Carcinoid tumor       1/15 (7%)   Pancreatic endocrine tumors       5/11(45%)   Pheochromocytoma       1/3 (...
   high proportion (55%) removed for toxicity        Median time to treatment discontinuation for treatment-        rela...
Outline   Classification and grading of NET   Introduction to temozolomide   Inclusion and exclusion criteria   Regime...
Conclusion   Combination of temozolomide and thalidomide    seems to be an active oral regimen for the    treatment of me...
Phase ii study of temozolomide and thalidomide
Phase ii study of temozolomide and thalidomide
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Phase ii study of temozolomide and thalidomide

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Transcript of "Phase ii study of temozolomide and thalidomide"

  1. 1. Phase II Study of Temozolomide and Thalidomide in Patients With Metastatic Neuroendocrine Tumors J Clin Oncol. 2006 Jan 20;24(3):401-6. Vs 劉俊煌 CR 周益聖
  2. 2. Outline Classification and grading of NET Introduction to temozolomide Inclusion and exclusion criteria Regimen dosage and adjustment Response assessment Result Disscusion Conclusion
  3. 3. Pancreas 2010;39: 707 - 712)
  4. 4. Pancreas 2010;39: 707 - 712)
  5. 5. Endocr Relat Cancer. 2004 Mar;11(1):1-18.
  6. 6. Endocr Relat Cancer. 2004 Mar;11(1):1-18.
  7. 7. Outline Classification and grading of NET Introduction to temozolomide Inclusion and exclusion criteria Regimen dosage and adjustment Response assessment Result Disscusion Conclusion
  8. 8. Cancer Chemother Pharmacol(2009) 64:647–655
  9. 9. Cancer Chemother Pharmacol(2009) 64:647–655
  10. 10. J Clin Oncol 25:4127-4136
  11. 11. Temozolomide dosing regimens for malignant gliomas J Clin Oncol 25:4127-4136
  12. 12. The Oncologist 2007;12:1114–1123
  13. 13. The Oncologist 2007;12:1114–1123
  14. 14. Outline Classification and grading of NET Introduction to temozolomide Inclusion and exclusion criteria Regimen dosage and adjustment Response assessment Result Disscusion Conclusion
  15. 15. Inclusion (1) Histologically confirmed, locally unresectable or metastatic neuroendocrine tumors Prior treatment with chemotherapy, other than DTIC, temozolomide, or thalidomide, was permitted ECOG performance status of 0, 1, or 2 Life expectancy > 12 weeks Adequate renal function (serum creatinine < 1.5 * the upper limit of normal [ULN])
  16. 16. Inclusion (2) Adequate hepatic function (total and direct bilirubin < 2 * the ULN) ALT and AST < 5 * the ULN, and alkaline phosphatase < 2 * the ULN or < 5 * the ULN in the setting of liver metastases Adequate bone marrow function (absolute neutrophil count >1,500/mm3, platelets > 100,000/mm3, hemoglobin >9 g/dL)
  17. 17. Exclusion Clinically apparent CNS metastases or carcinomatous meningitis History of myocardial infarction 6 months before protocol treatment History of major surgery within 2 weeks before treatment initiation HIV infection or AIDS-related illness Other serious medical or psychiatric illness Insufficient recovery from toxicities of prior therapies Pregnant or lactating.
  18. 18. Outline Classification and grading of NET Introduction to temozolomide Inclusion and exclusion criteria Regimen dosage and adjustment Response assessment Result Disscusion Conclusion
  19. 19. Treatment Program Temozolomide  150 mg/m2 days 1 to 7 and days 15 to 21 Thalidomide  daily  starting dose of 200 mg Every 28 days
  20. 20. Temozolomide adjustment Hold if  ANC less than 1,000/mm3  Plt less than 50,000/mm3  all nonhematologic toxicities with National Cancer Institute Common Toxicity Criteria grade 2 or higher Not resumed until full hematologic recovery On recovery, dose reduction of 50 mg/m2 Discontineud if  Unable to resume therapy within 3 weeks  Unacceptable toxicity levels
  21. 21. Thalidomide adjustment Increased weekly by 100 mg until a maximum dose of 400 mg Before escalation  Toxicity >> reduced by 100 mg/d  No improvement within 7days >> further reduced by 50 mg  Not tolerate 50 mg/d >> removed from study After escalation  Toxicity >> decreased by 100 mg  not resolved to grade 1 within 7 days >> further reduced by 100 mg  Pt at a dose of 100 mg >> reduction to 50 mg daily
  22. 22. Outline Classification and grading of NET Introduction to temozolomide Inclusion and exclusion criteria Regimen dosage and adjustment Response assessment Result Disscusion Conclusion
  23. 23. Response assessment Every 8 weeks after initiation of treatment Computed tomography scan Pt with complete [CR] or partial response [PR] or stable disease remained on treatment until progression CR  disappearance of all target lesions  at least 4 weeks
  24. 24. Response assessment PR  decrease of more than 30% in the sum of the largest perpendicular diameters of all measurable lesions  at least 4 weeks  without progression of any nonmeasurable sites  Without new lesions. Progressive disease  increase of 20% or more in the sum of longest diameters of target lesions  one or more new lesions
  25. 25. Response assessment Stable disease:  Neither PR, nor progressive disease Biochemical response  secondary end point  PR:decrease in chromogranin A by 50% or more  Stable: <50 % decrease or <25% increase
  26. 26. Outline Classification and grading of NET Introduction to temozolomide Inclusion and exclusion criteria Regimen dosage and adjustment Response assessment Result Disscusion Conclusion
  27. 27. Duration of Treatment 29 patients received treatment for a median of 7.3 months (range, 1 to 23 months) 1 patient required dose reduction of temozolomide due to thrombocytopenia 16 patients required dose reductions for thalidomide- related toxicities  14 required dose reduction to 100 mg  2 required dose reductions to 50 mg daily 9 patients continued thalidomide at their starting dose of 200 mg 4 patients able to undergo dose escalation to 400 mg Median thalidomide dose 100 mg/d
  28. 28. Treatment-related toxicities resulting in discontinuation:neuropathy (11 patients,38%, 6 pts persist > 3 wks), infection(four patients), thrombocytopenia (four patients), neutropenia(one patient), rash (one patient). Infections included: Pneumocystis carinii pneumonia(one patient), disseminated varicella zoster virus (one patient),staphylococcal sepsis (one patient), cutaneous herpes zoster(one patient)
  29. 29. Median time to treatmentdiscontinuation for toxicity :8.4months (range, 1.5 to 7.5 months)
  30. 30. Median duration of response was 13.5months (range, 2 to 31 months)
  31. 31. Progression-free survival Overall survival 1-year survival rate: 79% 2-year survival rate: 61%
  32. 32. Outline Classification and grading of NET Introduction to temozolomide Inclusion and exclusion criteria Regimen dosage and adjustment Response assessment Result Disscusion Conclusion
  33. 33. Discussion Overall objective radiologic response rate of 25%(CR+PR) Biochemical response rate of 40% 2-year survival rate of 61% Unique toxicities:neuropathy(38%) and selective lymphopenia(69%)
  34. 34.  Carcinoid tumor  Objective response rates of streptozocin-based regimens: 16% to 33% J Clin Oncol 2:1255-1259, 1984 Cancer Clin Trials2:327-334, 1979 J Clin Oncol 23:4897-4904, 2005 Pancreatic endocrine tumors  Combined biochemical and radiologic response rate of . Streptozocin and doxorubicin : 69% N Engl J Med 326:519-523, 1992  Overall response rate of retrospective study of streptozocin, fluorouracil, and doxorubicin:39%  J Clin Oncol 22:4762-4771, 2004  Cancer 86:944-948, 1999  Am JClin Oncol 27:485-488, 2004
  35. 35. CR+PR Carcinoid tumor  1/15 (7%) Pancreatic endocrine tumors  5/11(45%) Pheochromocytoma  1/3 (33%)
  36. 36.  high proportion (55%) removed for toxicity  Median time to treatment discontinuation for treatment- related toxicity:8.4 months 4 patients experienced progressive disease while receiving study therapy Prophylaxis against P carinii pneumonia and herpes simplex virus should be utilized
  37. 37. Outline Classification and grading of NET Introduction to temozolomide Inclusion and exclusion criteria Regimen dosage and adjustment Response assessment Result Disscusion Conclusion
  38. 38. Conclusion Combination of temozolomide and thalidomide seems to be an active oral regimen for the treatment of metastatic neuroendocrine tumors and alternative to intravenous regimens More active in pancreatic endocrine tumors than in carcinoid tumors. Further studies to more precisely assess the relative efficacy of this regimen in pancreatic endocrine and carcinoid tumors Also to assess the relative contributions of temozolomide and thalidomide to the antitumor activity
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