ACE ALP APTT ALT ARB AST AUC AUC0-24 Cmax CTCAE DBP ft3 ft4 GOT GPT LLN LVEF MUGA NYHA PS PT PT-INR QTc SBP TSH ULN 24 Common Terminology Criteria for Adverse Events New York Heart Association QT 1
3 4 5 5 9 13 15 17 20 20 21 27 31 QT 33 35 41 41 41 41 41 41 41 41 41 42 42 42 44 44 44 44 44 44 44 44 45 Q&A 48 54 1 55 2 60 3 QT 69 4 WHOPS 70 5 NYHA 70 6 71 73 2
/2012 9 2014 3 http://votrient.jp 3
4 Q&A 5 5 71 13 9 17 20 15
6 7 1 2 1 2 9 3 4 5 QT QT 6 7 8 9 Q&A52 5
WHO 2002 / / MFH MFH MFH PNET / PEComa GIST MPNST / Q&A
WHO classification of soft tissue sarcoma 2002 TUMOUR TYPE SUBTYPE Adipocytic liposarcoma Dedifferentiated Myxoid/Round cell Pleomorphic Mixed-type Well differentiated Fibroblastic Adult fibrosarcoma Myxofibrosarcoma Sclerosing epithelioid fibrosarcoma Solitary fibrous tumour Desmoid type fibromatosis Low grade fibro myxoid sarcoma/hyalinizing spindle cell tumour Inflammatory myofibroblastic sarcoma So-called fibrohistiocytic tumours Undifferentiated pleomorphic sarcoma pleomorphic MFH Undifferentiated pleomorphic sarcoma with giant cells Giant cell MFH Undifferentiated pleomorphic sarcoma with prominent inflammation Inflammatory MFH Smooth muscle tumours Leiomyosarcoma excluding skin Pericytic perivascular Malignant glomus tumour tumours Skeletal muscle tumours Embryonal incl. spindle cell, botryoid, anaplstic rhabdomyosarcoma Alveolar rhabdomyosarcoma incl solid anaplastic Pleomorphic rhabdomyosarcoma Vascular tumours Epithelioid haemangioendothelioma Angiosarcoma Chondro-osseous tumours Mesenchymal chondrosarcoma Extraskeletal osteosarcoma Tumors of uncertain differentiation Synovial sarcoma Epithelioid sarcoma Alveolar soft part sarcoma Clear cell sarcoma Extraskeletal myxoid chondrosarcoma PNET/Extraskeletal Ewing tumour Desmoplastic small round cell tumour Extra-renal rhabdoid tumour Malignant mesenchymoma Neoplasms with perivascular epithelioid cell differentiation PEComa Intimal sarcoma GIST MPNST Dermatofibrosarcoma protuberans Undifferentiated sarcoma NOS OTHER specify / 7
8 2-5 NYHA70-6 71 WHOPS 1 0 1 SBP 140mmHg DBP 90mmHg 1.5 10 9 /L 100 10 9 /L 9g/dL PT 1.2 ULN INR PT INR APTT APTT 1.5 ULN 200mg 200mg AST GOT 2.5 ULN ALT GPT 1.5mg/dL 0.15g/24hr TSH ft4 ft3 12 LLN MUGA 50 LVEF 18 18 6 NYHA 2 ULN LLN 1-4 WHOPS 70 Q&A
1 1 800mg 200mg 412 1.5 ULN 1 1 800mg12 200mg 200mg 1 800mg 200mg 200mg 200mg 200mg 1 200mg 200mg 9
800mgAUC Cmax AUC 2.3 1.9 Cmax2.1 4 3 2 1 2 3 4 1 2 1 1 68 91 5 6 7 8 9 10 11 1 2 2 2 18 19122 17 18 19 20 21 22 23 1 2 10 1 2 Q&A
200mg 200mg 1 800mg 800mg ALT 8.0 ULN ALT 3.0 ULN 2400mg -24 11
QT -24 28 32QT 34 Grade 1 Grade 2/3 Grade 4 Grade 1 Grade 1 Grade 1 1 Grade 2/3 14 200mg 1 800mg Q&A
ヴォトリエントを 服用する 患者さんへ 監修独立行政法人国立がん研究センター中央病院骨軟部腫瘍科 リハビリテーション科医長川井章先生 13
14 Q&A
/ WHO PS PT AST ALT ALP TSH ft4 ft3 12 MUGA CT MRI QT Torsade de pointes LVEF QT Torsade de pointes QT QT 15
12 1 2 4 6 8 10 12 2 4 8 4 4 4 4 4 4 4 4 4 4 4 4 1 2 4 4 4 4 12 3 MUGA 1 PT 2 AST ALT ALP 3 TSH ft4 ft3 4 Q&A
in vitro P450 CYP 3A4CYP1A2 2C8 CYP3A4 CYP 2B6 2C8 2E1 3A4UGT1A1 OATP1B1 P- PgpBCRP breast cancer resistance protein CYP3A4CYP3A4 AUC Cmax4042 1 CYP3A4 CYP3A4 CYP3A4AUC Cmax 6645 CYP3A4 CYP3A4 HIV 17
18 Q&ACYP3A4 CYP3A4 AUC Cmax 5435 CYP3A4 50mg40mg 10mg8mg 1.5mg HIV AUC26Cmax31 CYP3A4 CYP2C8 AUC Cmax 5951 ALT GPT
19
20 Q&A QTTorsade de pointes
AST ALT 16 24 http://www.mhlw.go.jp/topics/2006/11/dl/tp1122-1i01.pdf 2 28.4308/1084 1 4.611/240 Grade 3 4.210/240 235.1296/844 1-1 55 n n=240 n=31 Grade Grade 3 Grade Grade 3 ALT 8 3.3 6 2.5 1 3.2 1 3.2 AST 5 2.1 5 2.1 0 0 -GTP 4 1.7 3 1.3 0 0 2 0.8 0 0 0 AST 1 0.4 1 0.4 0 0 1 0.4 2 0 0 0 ALP 1 0.4 0 0 0 2 Grade CTCAE ver.3.0 2ALT 3 518 ALT 8135 ALT 20 5 21
1 8 11 5 100 4 80 3 60 2 40 1 20 0 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 1 3 0 4 2 0 1 1 4 4 8 10 10 11 9.1 36.4 36.4 72.7 90.9 90.9 100 ALT 3ALT 1818565292.9 ALT 3 Q&A
190 210 220 9 2 92080 ALT 3 4082042 3 55 88 2020 ALT 45402929 ALT 381%9 91%18 ALT 3 ALT 20 15 10 5 0 ALL ALT 3 ULN ALL ALT 3-8 ULN ALL ALT 8 ULN 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 200 230 92080 ALT 3 ULN 95 CI p vs 1.3 1.01-1.67 0.0456 60 vs 60 0.61 0.49-0.77 0.001 ALTULN vs ULN 0.53 0.36-0.77 0.001 vs 1.88 1.45-2.43 0.001 PS WHO/ECOG 0 KPS 100-90 vs WHO/ECOG 1-2 KPS 90 ALT 5 ULN 1.56 1.22-2.00 0.001 60 vs 60 0.61 0.45-0.84 0.0024 ALTULN vs ULN 0.6 0.36-0.99 0.0476 vs 1.45 1.06-1.98 0.0188 ALT 8 ULN 60 vs 60 0.56 0.37-0.85 0.0072 n=2080 n=1149 n=382n=549n=2080alt 23
ALT3 ALT 3.0 ULN 3.0 ULN ALT 8.0 ULN ALT>8.0 ULN ALT>3.0 ULN 2.0 ULN 2.0 ULN >2.0 ULN >35 1 1 1 ALT 3.0 ULN ALT 3.0 ULN 1 1 2 2 1 8 1 ALT 3.0 ULN ALT>3.0 ULN 1 1 ALT>3.0 ULN >2.0 ULNALT>5.0 ULN 21800mg 400mg1600mg 200mg2 Grade CTCAE ver.4.0 3 Grade 1 Grade 2 Grade 3 Grade 4 ULN 3.0 ULN 3.0 5.0 ULN 5.0 20.0 ULN 20.0 ULN ULN 1.5 ULN 1.5 3.0 ULN 3.0 10.0 ULN 10.0 ULN ULN Q&A
1 1 70 800mg 33 PS 0 800mg 14 20 CT 26 34 CHDF 4 16 20 3 AST IU/L 51 22 42 2141 2324 915 ALT IU/L 21 14 12 642 622 253 mg/dl 0.9 1.1 1.2 4.8 5 4.4 PT 64 - - 10 10 23 IU/L 2500 2000 AST ALT T-Bil mg/dl 10 8 ALT AST 1500 1000 6 4 500 2 0 0 20 10 0 10 20 30 40 50 800mg/ 25
1 800mg 800mg 60 19 19 600mg 20 600mg 6 26 50 400mg 51 400mg 31 81 23 12 19 26 29 33 43 51 58 68 2 4 8 LDH IU/L 131 116 123 146 181 177 222 427 352 315 182 141 299 141 GTP IU/L 39 30 32 34 32 39 36 56 66 95 149 119 116 115 AST IU/L 20 18 18 21 21 23 83 391 355 311 105 37 328 51 ALP IU/L 396 323 329 379 346 392 388 459 508 492 451 428 493 395 mg/dl 0.7 0.6 0.7 1 0.9 0.9 0.8 1.2 0.8 0.7 0.6 0.6 0.9 0.9 ALT IU/L 16 17 18 18 19 22 85 532 577 521 243 80 554 115 IU/L mg/dl 700 2.0 AST 600 ALT 1.8 T-Bil 1.6 500 1.4 1.2 400 1.0 300 0.8 200 0.6 0.4 100 0.2 0 0.0 30 20 10 0 10 20 30 40 50 60 70 800mg/ 400mg/ 600mg/ ALT AST 2 Q&A
16 28 4 2 42.0455/10840.66/1084 39.294/240 Grade 3 6.616/240 2 42.8361/844 7.16/844 n n=240 n=31 Grade Grade 3 Grade Grade 3 94 39.2 16 6.6 16 51.6 5 16.1 CTCAE ver.3.0 40 9 9018 27
SBP 140mmHg SBP 160mmHg 140<SBP<160mmHg90<DBP<100mmHg DBP 90mmHg DBP 100mmHg 20mmHg DBP 2 1 1 2 2 1 1 1 1 1 2 1 SBP 140mmHgDBP 90mmHg 2-11 SBP DBP <> Grade CTCAE ver.4.0 3 Grade 1 Grade 2 Grade 3 Grade 4 1 2 120-139mmHg 140-159mmHg 160mmHg 80-89mmHg 90-99mmHg 100mmHg 2 24 2 0 m m H g 140/90mmHg Q&A
1 1 1 2014 5 ARB ACE 4 ARB ACE ACE Step 1 Step 2 Step 3 5mg 1 150mg 1 1 10mg 1 15mg 1 150mg 1 1 80 80 10mg 20mg25mg 1 1 29
Q&A30
LVEF 38220.5 LVEF 13 LVEF LVEF ( ) 16 32 http://www.mhlw.go.jp/topics/2006/11/dl/tp1122-1k05.pdf 2 2.830/1084 5.413/240 Grade 3 1.33/240 n n=240 n=31 Grade Grade 3 Grade Grade 3 13 5.4 3 1.3 2 6.5 0 CTCAE ver.3.0 31
LVEF LVEF LVEF 15 LVEF LLN 5 LVEF LLN LVEF 2 4 LVEF LVEF LLN LVEF LLN 2 4 50 Grade CTCAE ver.4.0 3 Grade 1 Grade 2 Grade 3 Grade 4 BNP E F 5 0 - EF 40- EF20 4010-2 0 20 20 Q&A
QT QTTorsade de pointes QT 16 34 QT -3 QT69 2 0.67/1084 QT0.11/1084 QT 0.82/240 Grade 3 0.41/240 Torsade de pointes 11/554 Torsade de pointes QT n n=240 n=31 Grade Grade 3 Grade Grade 3 QT 2 0.8 1 0.4 0 0 CTCAE ver.3.0 33
QT QT 12 QT QTc 0.48 QTc>0.48 0.48 <QTc 0.50 QTc 0.50 BazettECG Grade CTCAE ver.4.0 3 Grade 1 Grade 2 Grade 3 Grade 4 QT QTc 0.45 0.48 QTc 0.481 0.50 2 QTc 0.501 QTc 0.501 0.60 Torsade de pointes / ; Q&A
http://www.mhlw.go.jp/topics/2006/11/dl/tp1122-1b01.pdf 0.4% 1/240 2 12 Grade CTCAE ver.4.0 3 Grade 1 Grade 2 Grade 3 Grade 4 / 35
SpO2 XCT CCRPLDH KL-6 SP-D 60 36 Q&A
1 1 70 800mg 72 200mg 4 / 71 - CT 7 1g/ 5 6g 10 15 20mg 16 17 1g/ 18 32 60mg 550mg 340mg 7 20 32 27 51 59 71 1 7 WBC10 3 / L 13.9 9.7 7.8 7.0 % 94.9 80.2 81.2 83.7 LDH IU/L 458 311 303 349 CRP mg/dl 1.36 2.59 1.90 16.31 KL-6 U/mL 240.0 478.4 1821.6 SP-D ng/ml 240.9 37
38 Q&A CT X
2 1 70 800mg 48 600mg 28 400mg 29 200mg 4 / 48 600mg 62 CT 76 400mg 104 1 4 100mg/ 35mg/ 18 30mg/ 56 5 600mg 400mg 2 13 14 20 WBC10 3 / L 5.2 5.2 8.2 8.8 9.1 LDH IU/L 309 233 204 327 212 276 CRP mg/dl 0.17 0.26 0.49 5.61 0.26 0.19 PCO2 mmhg 27.7 32.6 PO2 mmhg 71.7 77.8 KL-6 U/mL 859 1011 SP-A ng/ml 119.0 SP-D ng/ml 151.8 39
40 Q&A CT X
3 n=1,084 1.8 1.1 13.2 0.5 12.6 0. 1 12.5 n=240 1 0.4 10.4 7 2.9 1 0. 4 1 0. 4 1 6 6.7 10.410.4 166.7 10.4 177.1 10.4 20.8 /3 3 8.6 229.2 0.4 0.1 10.4% 10.4 41
42 Q&A 3 n=1,084 n=240 RPLS RPLS RPLS 3.8 7 13162 0.4 10.2 428 10.2 0.1% 1 2014 11 303
43
44 Q&A 3 n=1,084 n=240 53.6 13054.2 http://www.mhlw.go.jp/topics/ 2006/11/dl/tp1122-1g17.pdf 41.5% 6.1% 12652.5 10.4 37.1 22.3 11648.36125.4 12 34.2 11.0 7.6 218.866 27.5 2510.4 16.1 3.5 3515 10.0% 12 7.6% 8.9% 12
2 0.55/1084 2.15/240 2 n n=240 n=31 Grade Grade 3 Grade Grade 3 5 2.1 1 0.4 0 0 CTCAE ver.3.0 12 <> Grade CTCAE ver.4.0 3 Grade 1 Grade 2 Grade 3 Grade 4 / 45
46 Q&A 1 60 (MFH) 7cm MFH 600mg 4 600mg 3 600mg 3 4 2 3 49 6 8 92-94% CT 133 161 173 20 26 :MFH CT
47
1. Q1 Q2 Q3 Q4 48 2. Q5 Q6 Q7 Q8 Q9 3. 1 1 2 1 800mg Q10 Q11 Q12 Q13 Q&AQ&A
1. Q1 A 2 Q2 A 1 19 12PF12 RECIST ver.1.0 CR PR SD 265/19 5 SD -1 55 49
Q4 A 200mg 200mg (mg) 100 1/6 Grade 4 200 1/12 1/11 Grade 3 Grade 3 1/6 2/4 AST Grade 4 AST Grade 4 400 AST Grade 4 ALT Grade 4 Grade 3 800 0/18 1/13 Grade 5 27 ALTALT 1.5 ALT 1.5 3 ALT 3 A 18 9 2130mg/kg/ 21 62 10mg/kg/ Q3 Q&A
2. Q5 A Cmax AUC Q6 A 1 2-10 Q7 A 12 1 Q8 1 1 2 A 50mg 100mg 350mg 2000mg1 1300mg 400mg1 2 800mg1 1 1 1 1 Q9 1 800mg A 1 800mg 1 800mg 50mg 2000mg 800mg 51
Q10 A A A 800mg2237.8 400/800mg n=3 800mg n=7 1000mg n=3 1 22 1 22 1 22 Cmax 25.1 55.8 22.9 40.6 21.3 53.9 g/ml 34.0 35.2 69.5 47.7 118.1 55.4 tmax 4.00 2.50 2.98 2.52 3.00 4.00 hr 3.00 23.722.00 3.001.97 5.951.92 3.972.97 3.003.00 4.05 AUC0-24 402 962 325 677 305 759 g hr/ml 17.7 46.3 76.7 45.5 128.6 63.8 t1/2 28.4 40.1 42.5 37.8 33.0 21.4 hr 35.9 67.2 31.6 47.2 23.8 60.7 C24 14.8 34.6 9.1 22.0 8.5 21.1 g/ml 12.7 47.2 90.1 48.4 139.6 80.5 CVtmax 400/800mg 1 400mg 2 800mg Q11 Q12 3. Q&A
Q13 A 28 53
54 Q&A 1 2 3 QT 4 WHOPS 5 NYHA 6
2 11 6 PALETTE PAzopanib explored in soft-tissue sarcoma - A phase Study 13 369 47 0/1 2 WHO PS 0 1 n=246 n=31 n=123 n=16 36947 / 6 7 WHOPS2 1 800mg1 1 PFS20.07.0 PFS 0.35 p 0.001 55
1.0 =123n=246 PFS95 CI 7.04.4 8.1 20.017.9 21.3 0.8 95 CI 1 0.35 0.26 0.48 p 1 2 0.001 PS1 p WHO 0.6 0.4 0.2 0.0 0 20 40 60 80 100 2 OS12.6 10.7 0.87 p=0.256 OS Kaplan-Meier 1.0 =123n=246 OS95 CI 10.7 9.0 13.1 12.6 10.9 14.9 0.8 95.57 CI 1 0.87 0.67 1.13 p 1 2 0.256 0.6 0.4 0.2 0.0 0 5 10 15 20 25 30 35 1 pwho PS 2 260 68 PFS Kaplan-Meier Q&A
WHO PS n=123 51.0 18-78 n=246 56.0 20-83 n=369 55.0 18-83 n=16 49.0 24-76 n- n=31 60.0 21-82 n=47 59.0 21-82 69 56 147 60 216 59 9 56 13 42 22 47 54 44 99 40 153 41 7 44 18 58 25 53 0 60 49 118 48 178 48 10 63 19 61 29 62 1 63 51 128 52 191 52 6 38 12 39 18 38 n n=123 n=246 n=16 n=31 49 40 109 44 5 31 8 26 13 11 25 10 3 19 2 6 5 4 7 3 1 6 2 6 4 3 6 2 2 13 3 10 11 3 1 0 1 3 2 2 11 2 13 0 0 11 0 1 3 PEComa 0 11 0 0 PNET / 2 2 0 0 0 6 5 8 3 2 13 0 4 3 8 3 0 3 10 0 3 1 0 0 0 21 0 0 / 0 11 0 0 MFH 11 9 20 8 0 4 13 MFH 0 11 0 0 5 4 15 6 0 4 13 MPNST 4 3 8 3 1 6 0 3 2 3 1 0 0 0 11 0 0 11 0 0 0 11 0 0 0 0 11 0 0 11 0 0 0 11 0 0 0 10 8 22 9 0 3 10 MFH WHO 20022008 6 ITT 57
n n=123 n=246 n=16 n=31 5 4 7 3 0 3 10 11 3 1 0 0 6 5 9 4 2 13 1 3 23 19 29 12 2 13 2 6 20 16 44 18 2 13 5 16 31 25 65 26 9 56 15 48 10 8 19 8 1 6 4 13 5 4 8 3 0 0 6 5 10 4 0 0 12 10 40 16 0 0 2 2 0 0 0 11 11 0 0 0 9 4 0 1 3 11 21 0 0 Connective Tissue Oncology Society / n n=123 n=246 n=369 n=16 n=31 n=47 123 100 246 100 369 100 16 100 31 100 47 100 19 15 31 13 50 14 7 44 10 32 17 36 26 21 43 17 69 19 6 38 7 23 13 28 4 3 10 4 14 4 0 0 0 1 110 89 232 94 342 93 12 75 25 81 37 79 2 67 54 132 54 199 54 5 31 7 23 12 26 3 28 23 51 21 79 21 1 6 1 3 2 4 4 9 7 16 7 25 7 0 0 0 1 121 98 242 98 363 98 93 76 164 67 257 70 2 35 28 69 28 104 28 2 42 34 85 35 127 34 trabectedin 2 22 18 38 15 60 16 mtor 2 3 2 11 4 14 4 53 43 105 43 158 43 114 93 224 91 338 92 14 88 27 87 41 87 75 61 128 52 203 55 7 44 16 52 23 49 3 15 12 11 4 26 7 6 38 3 10 9 19 1 2 trabectedin 3 Q&A
7 142 WHO4 800mg 1 1 17 800mg 1 1 12 CR PR SD 174 142 / 6 7 800mg 1 1 12progression-free rate PFCR PR SD 1 12PF 12 2 3 n 19 3 n 41 3 n 37 3 n 41 CR 0 0 0 0 PR 0 1 2 4 11 1 2 SD 5 26 4 16 39 14 38 16 39 PF CR+PR+SD 26 41 49 41 90%CI 11 0 47 6 28 4 55 5 34 3 63 2 28 4 55 5 1 12CR PR SD 2 1212 3 4 1 172SD2 CR PR SD 174 112 SD 2SD 142127895841 5337 5237 5136 4431 3525 59
24031 21991.3 13054.2 12652.5 11648.39439.2 9338.8 82 34.2 7330.4 6527.1 6125.4 1 844 29 79594.2 45153.436142.8 32438.429635.1 286 33.9 27832.9 24428.9 18421.8 181 21.4 17520.7 2 28.4 42.0 0.6 2.8 QT 0.6Torsade de pointes 0.1 1.8 1.113.20.5 12.60.1 12.5 8.60.4 0.10.13.80.1% 1 2 n n=240 31 SOC Grade PT 1 2 3 4 5 32 13 85 35 84 35 17 7 11 0 219 91 88 37 71 30 27 11 11 0 0 187 78 73 30 46 19 11 5 0 0 0 130 54 84 35 25 10 7 3 0 0 0 116 48 42 18 12 5 7 3 0 0 0 61 25 24 10 7 3 3 1 0 0 0 34 14 17 7 8 3 11 0 0 0 26 11 10 4 4 2 0 0 0 0 14 6 11 5 21 0 0 0 0 13 5 13 5 0 0 0 0 0 13 5 11 5 11 0 0 0 0 12 5 5 2 0 0 0 0 0 5 2 11 4 2 0 0 0 0 5 2 5 2 0 0 0 0 0 5 2 4 2 0 0 0 0 0 4 2 11 0 11 0 0 0 21 21 0 0 0 0 0 21 11 0 11 0 0 0 21 11 11 0 0 0 0 21 0 0 11 0 0 0 11 0 11 0 0 0 0 11 2 Q&A
n n=240 31 SOC Grade PT 1 2 3 4 5 0 0 11 0 0 0 11 11 0 0 0 0 0 11 0 11 0 0 0 0 11 11 0 0 0 0 0 11 0 11 0 0 0 0 11 0 0 11 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 0 0 11 0 0 11 0 11 0 0 0 0 11 11 0 0 0 0 0 11 0 11 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 0 11 0 0 0 11 68 28 42 18 25 10 11 11 0 137 57 63 26 39 16 23 10 11 0 0 126 53 8 3 21 11 0 0 0 11 5 6 3 21 0 0 0 0 8 3 5 2 21 0 0 0 0 7 3 4 2 0 21 0 0 0 6 3 21 0 0 0 0 0 21 0 11 0 0 0 0 11 0 11 0 0 0 0 11 0 11 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 0 0 0 11 0 11 81 34 41 17 8 3 11 0 0 131 55 66 28 27 11 0 0 0 0 93 39 27 11 6 3 21 0 0 0 35 15 21 9 6 3 0 0 0 0 27 11 10 4 12 5 4 2 0 0 0 26 11 25 10 0 0 0 0 0 25 10 10 4 4 2 0 0 0 0 14 6 10 4 0 0 0 0 0 10 4 10 4 0 0 0 0 0 10 4 3 1 0 0 0 0 0 3 1 3 1 0 0 0 0 0 3 1 0 21 11 0 0 0 3 1 11 11 0 0 0 0 21 21 0 0 0 0 0 21 11 0 0 0 0 0 11 0 0 0 11 0 0 11 61
n=240 31 SOC Grade PT 1 2 3 4 5 11 0 0 0 0 0 11 0 0 11 0 0 0 11 11 0 0 0 0 0 11 71 30 23 10 21 3 1 0 0 99 41 48 20 17 7 0 0 0 0 65 27 33 14 4 2 11 0 0 0 38 16 12 5 11 0 0 0 0 13 5 12 5 0 0 0 0 0 12 5 11 11 0 0 0 0 21 11 0 0 0 0 0 11 0 0 0 11 0 0 11 11 0 0 0 0 0 11 0 11 0 0 0 0 11 11 0 0 0 0 0 11 0 0 0 11 0 0 11 11 0 0 0 0 0 11 0 0 11 0 0 0 11 0 11 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 11 0 0 0 0 11 0 0 0 11 0 0 11 0 0 11 0 0 0 11 28 12 53 22 20 8 21 0 0 103 43 27 11 51 21 16 7 0 0 0 94 39 0 3 1 3 1 11 0 0 7 3 5 2 0 0 0 0 0 5 2 21 0 0 0 0 0 21 11 0 0 0 0 0 11 0 0 11 0 0 0 11 0 0 0 11 0 0 11 40 17 29 12 16 7 8 3 0 11 94 39 39 16 29 12 5 2 0 0 0 73 30 19 8 5 2 4 2 0 0 0 28 12 0 21 4 2 21 0 0 8 3 0 0 21 3 1 0 0 5 2 0 11 0 3 1 0 0 4 2 0 0 11 21 0 0 3 1 11 11 0 0 0 0 21 11 0 0 0 0 11 21 11 0 11 0 0 0 21 0 11 11 0 0 0 21 0 0 0 11 0 0 11 0 0 0 0 0 11 11 n Q&A
SOC PT n=240 31 Grade 1 2 3 4 5 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 0 11 0 0 0 11 11 0 0 0 0 0 11 / 0 0 0 0 0 11 11 0 0 0 0 0 11 11 47 20 25 10 13 5 0 0 0 85 35 46 19 25 10 11 5 0 0 0 82 34 21 0 21 0 0 0 4 2 11 0 0 0 0 0 11 0 0 11 0 0 0 11 48 20 13 5 3 1 11 0 11 66 28 16 7 21 0 0 0 0 18 8 14 6 21 0 0 0 0 16 7 7 3 4 2 0 0 0 0 11 5 6 3 21 21 0 0 11 11 5 0 4 2 0 11 0 0 5 2 3 1 0 0 0 0 0 3 1 3 1 0 0 0 0 0 3 1 21 0 0 0 0 0 21 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 0 11 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 44 18 6 3 5 2 0 0 0 55 23 21 9 4 2 21 0 0 0 27 11 20 8 21 11 0 0 0 23 10 6 3 0 0 0 0 0 6 3 21 0 11 0 0 0 3 1 21 0 0 0 0 0 21 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 0 11 0 0 0 11 0 11 0 0 0 0 11 0 0 11 0 0 0 11 11 0 0 0 0 0 11 3 1 15 6 4 2 0 0 0 22 9 21 21 0 0 0 0 4 2 0 21 0 0 0 0 21 0 21 0 0 0 0 21 n 63
n=240 31 SOC Grade PT 1 2 3 4 5 0 0 11 0 0 0 11 0 11 0 0 0 0 11 11 0 0 0 0 0 11 0 11 0 0 0 0 11 0 0 11 0 0 0 11 0 11 0 0 0 0 11 0 11 0 0 0 0 11 0 11 0 0 0 0 11 0 11 0 0 0 0 11 0 0 11 0 0 0 11 0 11 0 0 0 0 11 0 11 0 0 0 0 11 0 11 0 0 0 0 11 0 0 11 0 0 0 11 0 11 0 0 0 0 11 0 11 0 0 0 0 11 0 11 0 0 0 0 11 15 6 4 2 0 0 0 0 19 8 6 3 3 1 0 0 0 0 9 4 21 0 0 0 0 0 21 21 0 0 0 0 0 21 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 11 0 0 0 0 11 11 0 0 0 0 0 11 3 1 9 4 3 1 0 0 0 15 6 21 8 3 3 1 0 0 0 13 5 0 11 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 8 3 9 4 0 0 0 0 17 7 8 3 9 4 0 0 0 0 17 7 4 2 6 3 21 0 0 0 12 5 21 6 3 11 0 0 0 9 4 21 0 0 0 0 0 21 0 0 11 0 0 0 11 6 3 21 11 0 0 0 9 4 4 2 0 11 0 0 0 5 2 11 11 0 0 0 0 21 0 21 0 0 0 0 21 11 0 0 0 0 0 11 11 0 0 0 0 0 11 n Q&A
n n=240 31 SOC Grade PT 1 2 3 4 5 3 1 11 11 11 0 0 6 3 11 11 0 0 0 0 21 0 0 11 0 0 0 11 0 0 0 11 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 21 11 11 0 0 0 4 2 0 11 0 0 0 0 11 0 0 11 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 21 0 11 11 0 0 4 2 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 0 11 0 0 0 11 0 0 0 11 0 0 11 3 1 11 0 0 0 0 4 2 11 0 0 0 0 0 11 11 0 0 0 0 0 11 11 0 0 0 0 0 11 0 11 0 0 0 0 11 0 11 11 0 0 0 21 0 11 0 0 0 0 11 0 0 11 0 0 0 11 11 0 11 0 0 0 21 11 0 11 0 0 0 21 65
312993.5 ) 1858.1 1858.1 1651.6 1651.61651.6 1548.4 1445.2 1341.9 929.0 825.88 25.8722.6 n=31 SOC Grade PT 1 2 3 4 5 7 23 10 32 12 39 0 0 0 29 94 13 42 8 26 3 10 0 0 0 24 77 9 29 5 16 2 6 0 0 0 16 52 11 35 4 13 0 0 0 0 15 48 6 19 2 6 0 0 0 0 8 26 5 16 0 0 0 0 0 5 16 4 13 1 3 0 0 0 0 5 16 3 10 1 3 0 0 0 0 4 13 2 6 0 0 0 0 0 2 6 1 3 0 0 0 0 0 1 3 0 0 1 3 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 18 58 6 19 2 6 0 0 0 26 84 17 55 1 3 0 0 0 0 18 58 4 13 4 13 1 3 0 0 0 9 29 6 19 2 6 0 0 0 0 8 26 7 23 0 0 0 0 0 7 23 5 16 0 0 0 0 0 5 16 5 16 0 0 0 0 0 5 16 3 10 0 0 0 0 0 3 10 2 6 0 0 0 0 0 2 6 0 0 1 3 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 0 1 3 0 0 0 0 1 3 8 26 9 29 1 3 0 0 0 18 58 8 26 9 29 1 3 0 0 0 18 58 12 39 4 13 1 3 0 0 0 17 55 11 35 5 16 0 0 0 0 16 52 1 3 1 3 0 0 0 0 2 6 0 0 1 3 0 0 0 1 3 1 3 0 0 0 0 0 1 3 11 35 5 16 0 0 0 0 16 52 10 32 3 10 0 0 0 0 13 42 3 10 0 0 0 0 0 3 10 2 6 0 0 0 0 0 2 6 0 1 3 0 0 0 0 1 3 n Q&A
n n=31 SOC Grade PT 1 2 3 4 5 0 1 3 0 0 0 0 1 3 0 1 3 0 0 0 0 1 3 2 6 9 29 5 16 0 0 0 16 52 2 6 9 29 5 16 0 0 0 16 52 9 29 5 16 1 3 0 0 0 15 48 9 29 5 16 0 0 0 0 14 45 3 10 0 0 0 0 0 3 10 0 0 1 3 0 0 0 1 3 1 3 0 0 0 0 0 1 3 9 29 0 1 3 0 0 0 10 32 4 13 0 1 3 0 0 0 5 16 4 13 0 0 0 0 0 4 13 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 6 19 0 0 0 0 0 6 19 3 10 0 0 0 0 0 3 10 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 3 10 3 10 0 0 0 0 6 19 2 6 0 0 0 0 0 2 6 0 1 3 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 0 1 3 0 0 0 0 1 3 0 1 3 0 0 0 0 1 3 1 3 1 3 0 0 0 0 2 6 0 1 3 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 0 2 6 0 0 0 0 2 6 0 2 6 0 0 0 0 2 6 1 3 0 0 0 0 0 1 3 1 3 1 3 0 0 0 0 2 6 1 3 0 0 0 0 0 1 3 0 1 3 0 0 0 0 1 3 2 6 0 0 0 0 0 2 6 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 0 0 1 3 0 0 0 1 3 0 0 1 3 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 67
n=31 SOC Grade PT 1 2 3 4 5 0 1 3 0 0 0 0 1 3 0 1 3 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 1 3 0 0 0 0 0 1 3 n Q&A
3 QT 8 K Mg Ia Ic Ca torsades de pointes K 5-HT Ca PDE5 H2 OAB 69
0 1 2 50 3 50 4 class 1 class 2 class 3 class 4 70 5 NYHA 10 4 WHOPS 9 Q&A
6 / 6 7 1 55 59 200mg QT QT QT 71
WHOPS 0 1 4 WHOPS70 SBP140mmHg DBP 90mmHg 1.5 10 9 /L 100 10 9 /L 9g/dL PTINR1.2 ULN PT APTT1.2 ULN INR APTT 1.5 ULN 200mg AST GOTALT GPT) 2.5 ULN 200mg 1.5mg/dL 0.15g/24hr TSH ft4 ft3 12 MUGA LVEFLLN 50 18 18 6 NYHA 5 NYHA70 Q&A
1 2012., 2012 2 Powles T., et al.:eur J Cancer 51,1293-1302 2015 3 JCOG Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 http://www.jcog.jp/doctor/tool/ctcaev4j_20130409.pdf 4 http://merckmanual.jp/mmpej/print/sec07/ch071/ch071c.html 5 2014., 2014 6 VEG110727 7VEG20002 8 9., 2010 9 Cancer Research UK cancers in general-cancer questions and answers-performance status http://cancerhelp.cancerresearchuk.org/about-cancer/cancer-questions/performance-status 10 Criteria Committee of the New York Heart Association Disease of the heart and blood vessels. In:Nomenclature and Criteria for Diagnosis. 6th ed. Little Brown & Co., Boston 1964 73
Q&A74