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38% 26% A) Response to ifosfamide and mesna: 124 previously treated patients with metastatic or unresectable sarcoma 124 (J Clin Oncol 7: 126-131, 1989) 124 95 29 II 1 2,000mg/m 2 x 4 8g/m 2 21 21% CR 4 PR 22 64 26 60 p=0.03 3 23% 1,2 19 performance status p<0.01 p<0.01 WBC 1,000/ul - 3 -
49 B) An intergroup phase III randomized study of doxorubicin and dacarbazine with or without ifosfamide and mesna in advanced soft tissue and bone sarcomas / / / III (J Clin Oncol 11: 1276-1285, 1993) Southwest Oncology Group(SWOG) 60mg/m 2 1,000mg/m 2 60mg/m 2 1,000mg/m 2 7,500mg/m 2 III 10,000mg/m 2 21 18 85 52 / 170 / / 170 17 32 p<0.002 p<0.02 / / 84 7,500mg/m 2 6,000mg/m 2 / 13 / / 12 50 / European Organization for Research and Treatment of Cancer (EORTC) / CYVADIC / / / III Proc Am Soc Clin Oncol 9: 309, 1990 Eastern Cooperative Oncology Group (ECOG) / III 20% vs. 34%, p<0.03 vs.12 Proc Am Soc Clin Oncol 11: 413, 1992 C) Adjuvant chemotherapy for adult soft tissue sarcomas of the extremities and girdles: Results of the Italian randomized cooperative trial (J Clin Oncol 19: 1238-1247, 2001) 104 III 51 53 / / 1-4 -
60mg/m 2 x 2 120mg/m 2 1 1,800mg/m 2 x 5 g/m 2 3 5 16 48 p=0.04 46 75 p=0.03 / 2 13 4 19 p=0.04 D) Long-term results of the co-operative German-Austrian-Swiss osteosarcoma study group s protocol COSS-86 of intensive multidrug chemotherapy and surgery for osteosarcoma of the limbs - - COSS-86 (Ann Oncol 9: 893-899, 1998) 40 171 COSS-86 171 low-risk 41 high-risk 128 Low-risk 90mg/m 2, 4 12g/m 2, 12 120mg/m 2, 4 3 High-risk 90mg/m 2, 12g/m 2, 14 120mg/m 2, 6g/m 2, 5 4 171 10 72 66 Low-risk High-risk 10 75 66 72 67 high-risk 3 2 E) Phase II/III trial of etoposide and high-dose ifosfamide in newly diagnosed metastatic osteosarcoma: a pediatric oncology group trial II/III (J Clin Oncol 20: 426-433, 2002) Pediatric Oncology Group (POG) 1 100mg/m 2 x 500mg/m 2 1 3,500mg/m 2 x 17.5g/m 2 II/III G-CSF 6 5,000/uL 3 2 39 4 10 CR 19 49 PR 59 80 90 65 2 43 2 55 Grade 4 83 29 10 24 Fanconi 5 2 / - 5 -
2 F) Addition of ifosfamide and etoposide to standard chemotherapy for Ewing s sarcoma and primitive neuroectodermal tumor of bone / (N Engl J Med 348: 694-701, 2003) / Children s Cancer Group (CCG) Pediatric Oncology Group (POG) 4 1 1,800 mg/m 2 x 9g/m 2 1 100mg/m 2 x 500mg/m 2 III 518 3 17 49 120 5 5 62 22% 34% 58 22% 35% 398 5 5 200 54% 61% 198 69% 72% p<0.01 4 / (i) 20 4 1980 5 20 5 60 Cancer 35: 936-945, 1975 Cancer 49: 1221-1230, 1982, J Clin Oncol 10: 5-15, 1992 1985 1 1,800mg/m 2 x 9g/m 2 33 Cancer Treat Rep 69: 115-117, 1985 4 70 5 (Ann Oncol 9: 893-899, 1998) (J Clin Oncol 20: 426-433, - 6 -
2002) 3 (ii) VAC 1987 1 1,800 mg/m 2 x 9g/m 2 1 100mg/m 2 x 500mg/m 2 94% J Clin Oncol 5: 1191-1198, 1987 III 4 p<0.01 (N Engl J Med 348: 694-701, 2003) 1 (iii) 20% 2 II 356 300 26% Hematology and Oncology Clinics of North America 9: 765-785, 1995 16% 12% 13% Hematology and Oncology Clinics of North America 9: 765-785, 1995 Cancer 73: 2506-2511, 1994 2 Eastern Cooperative Oncology Group(ECOG) 80mg/m 2 60mg/m 2 7.5g/m 2 20% 34% p=0.03 J Clin Oncol 11: 1269-1275, 1993 European Organization for the Research and Treatment of Cancer (EORTC) 663 III 75mg/m 2 50mg/m 2 5g/m 2 23% 28% J Clin Oncol 13: 1537-1545, 1995 Southwest Oncology Group(SWOG) 60mg/m 2 1,000mg/m 2 60mg/m 2 1,000mg/m 2 7.5g/m 2 III / - 7 -
/ / 17 4 32 6 p<0.002 p<0.02 (J Clin Oncol 11: 1276-1285, 1993) G-CSF, GM-CSF Ann Oncol 9: 917-919, 1998, Am J Clin Oncol 21: 317-321, 1998 Cancer 80: 1221-1227, 1997 dose intensity 14 1568 Lancet 350: 1647-1654, 1997 1990 III 1 60mg/m 2 x 2 120mg/m 2 1 1,800mg/m 2 x 5 9g/m 2 3 5 p=0.04 (J Clin Oncol 19: 1238-1247, 2001) 1990 2004 4 Web 56 134 ifosfamide, adriamycin 49: 1333-1337, 1998 50: 711-715, 1999 ifosfamide Int J Clin Oncol : 36-40, 1999 Ifosfamide 37: 197-202 2000-8 -
43: 1067-1073, 2000 mesna, adriamycin, ifosfamide, dacarbazine (MAID) 51: 509-513, 2000 CYVADACT MAI(ifosfamide-adriamycin ) 52: 1361-1364, 2001 19: 209-215, 2003 77: 115-119, 2003 Ifosfamide, Doxorubicin and Cyclophosfamide Chemotherapy for Advanced Adult Soft Tissue Sarcoma: a Japanese Musculoskeletal Oncology Group Study. Proceedings Am Soc Clin Oncol 22, 825, 2003 acrolein sodium-2-mercapto-ethanesulfonate / (w/w) 60% J Clin Oncol 11: 1269-1275, 1993, J Clin Oncol 15:2378-2384, 1997, J Clin Oncol 19: 1238-1247, 2001 100% J Clin Oncol 13: 1600-1608, 1995 133% J Clin Oncol 11: 1276-1285, 1993 160%(J Clin Oncol 5: 1191-1198, 1987) 175% Ann Oncol 9: 917-919, 1998 100% 10 50 100g/m 2 J Clin Oncol 11: 173-190, 1993, Lancet 348: 578-580, 1996, Br J Cancer 82: 1636-1645, 2000 J Clin Oncol 9: 1495-1499, 1991, J Clin Oncol 11: 173-190, 1993-9 -
Curr Opin Pediatr 7: 208-213, 1995 Curr Opin Pediatr 7: 208-213, 1995 Med Pediatr Oncol 41: 190-197, 2003 performance status (J Clin Oncol 7: 126-131, 1989, Hematology and Oncology Clinics of North America 9: 767-768, 1995) 40 22 71 46 19 21 12g/m 2 g/m 2 x 147 3,4 76 3,4 10 3,4 11 15 22 39 14 13 19 13 29 J Clin Oncol 13: 1600-1608, 1995 53 18 65 33 20 120mg/m 2 g/m 2 1.8g/m 2 x 5 3,4 58 3,4 11 3,4 20 24 (J Clin Oncol 19: 1238-1247, 2001) 41 22 500mg/m 2 17.5g/m 2 3.5g/m 2 x 3,4 85 3,4 44 3,4 10 10 2 (J Clin Oncol 20: 426-433, 2002) G-CSF - 10 -
(i) EORTC 135 II g/m 2 24 3 18% 1.5g/m 2 Eur J Cancer Clin Oncol 23: 311-321, 1987 Antman 124 95 29 II 2,000mg/m 2 x 4 g/m 2 21 (J Clin Oncol 7: 126-131, 1989) 4 26 24 - J Clin Oncol 8: 170-178, 1990, Cancer Chemother Pharmacol 31: S174-179, 1993, Semin Oncol 23: 22-26, 1996 Le Cesne 40 28 ~10g/m 2 g/m 2 x 12g/m 2 33 PR 22 J Clin Oncol 13: 1600-1608, 1995 MD Shreyaskumar 14g/m 2 J Clin Oncol 15: 2378-2384, 1997 14g/m 2 74 29 40 19 g/m 2 2 12 7 14g/m 2 57 45 ~10g/m 2 12g/m 2 (ii) 40 75mg/m 2 10g/m 2 30 50 Eur J Cancer 26: 558-561, 1990, J Clin Oncol 11: 15-21, 1993, J Clin Oncol 11: 1276-1285, 1993, J Chemother 8: 224-228, 1996 G-CSF dose intensity Ann Oncol 9: 917-919, 1998, Am J Clin Oncol 21: 317-321, 1998-11 -
90mg/m 2 10 12.5g/m 2 Souhami RL, ed. Oxford Textbook of Oncology 2 nd ed. p2516 POG 500mg/m 2 17.5g/m 2 II/III 59 CR 10%, PR 49 2 55 (J Clin Oncol 20: 426-433, 2002) - ~10g/m 2 12g/m 2 14g/m 2 40 75mg/m 2 10g/m 2 G-CSF - 12 -