<4D F736F F D B160A5CEA4C6BEC7AA76C0F8B342A4E8B6B02E646F63>

Transcription

1 壹 非小細胞肺癌 治療方式 藥物種類 劑量劑量 間隔 *Gemcitabine (Gemzar ) Lung Cancer Chemotherapy Regimen Gemcitabine (Gemzar ) 1000mg/ m2 D1,D8,D15 +Cisplatin(Kemoplat ) 60-75mg/ m2 D1 Gemcitabine (Gemzar )1000mg/ m2 D1,D8,D15 +Carboplatin (Kemocarb ) (AUC=5) D1 Gemcitabine (Gemzar ) 1000mg/ m2 D1,D8,D15 *Vinorelbine (Navelbine ) Vinorelbine (Navelbine ) 20-25mg/ m2 D1,D8,D15 Vinorelbine (Navelbine ) 20-25mg/ m2 D1,D8,or D15+Cisplatin(Kemoplat ) 60-75mg/ m2 D1 Vinorelbine (Navelbine ) 20-25mg/ m2 D1,D8,or D15+Carboplatin (Kemocarb ) (AUC=5) D1 治療時間 Q28days 4-6cycles Q28days 4-6cycles Q28days 4-6cycles Q28days 4-6cycles Q28days 4-6cycles Q28days 4-6cycles 備註 CCr 60 CCr<60 CCr 60 CCr<60 Vinorelbine (Navelbine ) ORAL 20mg Q3W 前三次依體表面積每週給藥 *Paclitaxel (Genataxyl ) Paclitaxel (Genataxyl ) mg/ m2 D1,D8,D15 Paclitaxel (Genataxyl ) mg/ m2 D1,D8,D15 +Cisplatin(Kemoplat ) 60-75mg/ m2 D1 Paclitaxel (Genataxyl ) mg/ m2 D1,D8,D15 +Carboplatin (Kemocarb ) (AUC=5) D1 *Docetaxel (Taxotere ) Docetaxel (Taxotere ) 30-35mg/ m2 D1,D8,D15 Docetaxel (Taxotere ) 30-35mg/ m2 D1,D8,D15 +Cisplatin(Kemoplat ) 60-75mg/ m2 D1 Docetaxel (Taxotere ) 30-35mg/ m2 D1,D8,D15 +Carboplatin (Kemocarb ) (AUC=5) D1 Docetaxel (Taxotere ) 60-75mg/ m 2 D1 Docetaxel (Taxotere ) 60-75mg/ m 2 D1 +Cisplatin(Kemoplat ) 60-75mg/ m2 D1 Docetaxel (Taxotere ) 60-75mg/ m 2 D1 +Carboplatin (Kemocarb ) (AUC=5) D1 Q28days 4-6cycles Q28days 4-6cycles Q28days 4-6cycles Q28days 4-6cycles Q28days 4-6cycles Q28days 4-6cycles Q21days 4-6cycles Q28ays 4-6cycles Q28ays 4-6cycles 60mg/m2 一次, 第四次開始增 加每週 80mg/m2 一次 CCr 60 CCr<60 CCr 60 CCr<60 CCr 60 CCr<60 1

2 *Pemetrexed (Alimta ) Pemetrexed (Alimta ) 500mg/ m2 D1 Q21days 4-6cycles CCr 60 Pemetrexed (Alimta ) 500mg/ m2 D1 Q21days CCr 60 +Cisplatin(Kemoplat ) 60-75mg/ m2 D1 4-6cycles Pemetrexed (Alimta ) 500mg/ m2 D1 Q21days CCr<60 + Carboplatin (Kemocarb ) (AUC=5) D1 4-6cycles Gefitinib (Iressa ) 250 mg QD 需經健保事前審查核准後使用 Erlotinib (Tarceva ) 150 mg QD 需經健保事前審查核准後使用 *UFUR mg QD or 200 mg BID size > 3 cm * 可當 adjuvant chemotherapy Alimta 需經健保事前審查核准後使用 Alimta 需經健保事前審查核准後使用 Alimta 需經健保事前審查核准後使用 Indication: Adeno, pt2 and tumor 2 years 貳 小細胞肺癌 治療方式 藥物種類 劑量劑量 間隔 Etoposide(VP-16) (Eposin ) 100 mg/m2 D1-D3 +Cisplatin(Kemoplat ) 60-75mg/m2 D1 Etoposide(VP-16) (Eposin ) 100 mg/m2 D1-D3 +Carboplatin (Kemocarb ) (AUC=5) D1 Cyclophosphamide (Syklofosfamide ) 500mg/m2 D1 +Epirubicin (Pharmorubicin ) 50mg/m2 D1 +Cisplatin(Kemoplat ) 50mg/m2 D1 Cyclophosphamide (Syklofosfamide ) 500mg/m2 D1 + Epirubicin (Pharmorubicin ) 50mg/m2 D1 +Carboplatin (Kemocarb ) (AUC=5) D1 治療時間 備註 Q21-28 days 6 cycles Ccr 60 Q21-28 days 6 cycles Ccr<60 Q21-28 days 6 cycles Ccr 60 Q21-28 days 6 cycles Ccr<60 2

3 Hepatoma Chemotherapy Regimen 治療方式 Intra-hepatic and Subselective intra-aortic infusion --- Subselective intra-aortic --- Regimen I (A) Continuous infusion of 5FU (50~250mg) a day using a portable pump Regimen I (B) Intermittent one shot of Epirubicin (10~20mg) + Mitomycin C (2~8mg) Regimen I (C) Continuous infusion of 5FU (50~250mg) a day using a portable pump Intermittent one shot of Epirubicin (10~20mg) + Mitomycin C(2~8mg) regimenⅡ Intermittent one shot of Oncovin(2mg) RegimenⅢ Intermittent one shot of Cisplatin(10-30mg) Regimen Ⅳ Day1 VP-16(50mg~mg) 30min + Cisplatin(150mg~mg) 30min + Epirubicin (60mg~mg) 30min Day2 5FU(500mg- mg) 24hr 一天每 15 天為 1 cycle( 每 15 天打一次 ) 處方內容 Regimen I(A): 1 st week 5FU(50-500mg) --Intra-hepatic artery Chemotherapy A -- 2 nd week 5FU(50-500mg)+Epirubcin(10-40mg) 3 rd week 5FU(50-500mg) 4 th week 5FU(50-500mg)+Epirubcin(10-40mg)+Mitomycin-C (2-10mg) Regimen I(B): Cisplatin(2-40mg) in N/S or D5W 150cc keep 150CC/hr 5 days 4weeks 5FU(50-500mg) + Leucovorin ( mg)in N/S or D5W 250cc keep 50CC/hrfor total 5hr 5 days 4weeks Regimen I(C): Cisplatin(2-40mg) in N/S or D5W 150cc keep 150CC/hr 5 days 4weeks Mitomycin-C(2-10mg) in N/S or D5W 150cc keep 150CC/hr 5 days 4weeks 5FU(50-500mg) + Leucovorin ( mg)in N/S or D5W 250cc keep 50CC/hr for total 5hr 5 days 4weeks 3

4 -- Intra-hepatic artery Chemotherapy B-- Regimen I(A): Cisplatin(2-40mg) in N/S or D5W 50CC KEEP 100CC/HR 5 days 5FU(50-500mg) in N/S or D5W 250cc KEEP 10CC/HR 5 days 與 Leucovorin ( mg)+n/s100cc KEEP 5CC/HR 5 days 同步使用 Regimen I(B): Cisplatin(2-40mg) in N/S or D5W 50CC KEEP 100CC/HR 5 days Mitomycin-C (2-10mg) in N/S or D5W 50CC KEEP 100CC/HR 5 days 5FU(50-500mg) in N/S or D5W 250cc KEEP 10CC/HR 5 days 與 Leucovorin ( mg)+n/s100cc KEEP 5CC/HR 5 days 同步使用 處方內容 Systemic Chemotherapy therapy (concesus Date: ) (1)Doxorubicin(or Epirubcin) is current acceptable mono-chemotherapy (2)Encourage patents who are suitable for chemotherapy enter clinical trial (3)All other therapy stated as experiment therapy Systemic oral chemotherapy (1) 5FU 200mg-400mg qd in divided dose Target therapy (1) Nexavar(sorafenib) 2# -4#/day in divided dose 4

5 治療方式 Colon Cancer & Rectum Cancer Chemotherapy Regimen Neoadjuvant or Adjuvant High Risk Stage II or Stage III regimen 1: 5FU:500 mg/ m2, Leucovorin:100 mg/ m2 D Cycle:Weekly for 6 of 8 weeks,3 cycles regimen 2: UFUR(Uracil(224mg)-Tegafur(100mg) Tegafur mg/ m2 /day bid /q28 天 /every 5 weeks,6 cycles High Risk Stage II or Stage III,IV regimen 3: Capecitabine /mg/ m2 bid /q14 /every3 weeks,8 cycles (StageII 需自費 ) StageIII CRC,StageIV MCRC(1) FOLFOX 4 第一天 : (1)Oxaliplatin(85mg/m2) + D5W 250ml ivd (2)Leucovorin(200mg/m2) + D5W 250ml ivd (Oxaliplatin 和 Leucovorin 同時滴 2hrs:keep 125ml/hr) (3)5FU(400mg/m2) + N/S 250ml ivd for 1hr 處方內容 (4)5FU (600mg/m2) + N/S 500ml ivd(keep 23 ml/hr for 22hrs) 第二天 : (1)5FU(400mg/m2) + N/S 250ml ivd for 1hr (2)5FU (600mg/m2) + N/S 500ml ivd(keep 23 ml/hr for 22hrs) (3)Leucovorin(200mg/m2) + D5W 250ml ivd(keep 125ml/hr for 2hrs) (5Fu 與 Leucovorin 一起滴 ) Cycle Q 14 days StageIV MCRC(2) FOLFIRI (1) Irinotecan (180mg/m2) + NS 5000 ml ivd 2 hrs keep 2hrs (2) Leucovorin (400mg/m2) + D5W 250ml ivd keep 2hrs (3) 5-FU (400mg/m2) + D5W 250 ml ivd for 2hr (4) 5-FU (2400mg/m2) + D5W 500 ml ivd (keep 46 hrs, rate:11ml/hr) Cycle Q 14 days 5

6 StageIV MCRC(3) FOLFOXIRI (1)Eloxatin(85 mg.kg/m2) +5%G/W 250ml ivd 2 hrs (2)Campto(130mg.kg/m2) +N/S 500ml ivd 2 hours (3)5FU(400mg.kg/m2) + N/S 250ml ivd for 2 (4)Leucovorin (200mg.kg/m2) + N/S 250ml hrs ivd ( 5FU(3) & Leucovorin (4) 同時滴 2 hrs) (5)5FU(600mg.kg/m2) + N/S 500ml ivd (keep 23 ml/hr for 22 hrs ) StageIV MCRC (with target therapy) FOLFOX 4 or FOLFIRI Cycle:Q 2 wk Cetuximab 1st week 400mg/m 2 Cetuximab 2nd week 250mg/m 2 Q 1 wk Or Cetuximab 1st week 400mg/m 2 Cetuximab 2nd week 500mg/m 2 Q 2 wk (KRAS:Wild type) Or Bevacizumab 5 mg/ kg Q 2 wk CCRT Rectal Cancer regimen 1: 5-FU + RT 處方內 5-FU 1000 mg/m2/d civi x 5 days during the first and fifth weeks of radiotherapy Concurrent radiotherapy 50.4 Gy 容 Surgery in 4-6 weeks 5-FU 500 mg/m2/d civi d1-5 q4w x 4 cycles 6

7 Stomach Cancer Chemotherapy Regimen 治療方式 Neoadjuvant or Adjuvant RESECTABLE ECF Preoperative Epirubicin 50 mg/m 2 iv bolus d1 q3w x 3 cycles Cisplatin (Abiplatin) 60 mg/m 2 iv d1 q3w x 3 cycles 5-FU 200 mg/m 2 /d civi x 24 weeks Adjuvant Epirubicin 50 mg/m 2 iv bolus d1 q3w x 3 cycles Cisplatin (Abiplatin) 60 mg/m 2 iv d1 q3w x 3 cycles 5-FU 200 mg/m 2 /d civi x 24 weeks 處方內容 UNRESECTABLE or METASTATIC DCF Docetaxel (Taxotere) 75 mg/m 2 iv d1 q3w x 8 cycles Cisplatin (Abiplatin) 75 mg/m 2 iv d1 q3w x 8 cycles 5-FU 750 mg/m 2 /d civi d1-5 q3w x 8 cycles ECF Epirubicin 50 mg/m 2 iv bolus d1 q3w x 8 cycles Cisplatin (Abiplatin) 60 mg/m 2 iv d1 q3w x 8 cycles 5-FU 200 mg/m 2 /d civi x 6 months ECX Epirubicin 50 mg/m 2 iv bolus d1 q3w x 8 cycles Cisplatin (Abiplatin) 60 mg/m 2 iv d1 q3w x 8 cycles Capecitabine (Xeloda) 625 mg/m 2 po bid x 6 months EOX Epirubicin 50 mg/m 2 iv bolus d1 q3w x 8 cycles Oxaliplatin (Eloxatin) 130 mg/m 2 iv over 2 hours d1 q3w x 8 cycles Capecitabine (Xeloda) 625 mg/m 2 po bid x 6 months FLO Oxaliplatin (Eloxatin) 85 mg/m 2 iv over 2 hours d1 q2w Leucovorin 200 mg/m 2 iv over 2 hours d1 q2w 5-FU 2600 mg/m 2 civi over 24 hours q2w FOLFOX 4 Leucovorin 200 mg/m 2 iv over 2 hrs before 5-FU, d1 and 2, q2w x 12 cycles 5-FU 400 mg/m 2 iv bolus and then 600 mg/m2 iv over 22 hrs, d1 and d2, q2w x 12 cycles 7

8 Oxaliplatin (Eloxatin) 85 mg/m 2 iv d1, q2w x 12 cycles XELOX&XP Capecitabine (Xeloda) 1000 mg/m 2 po bid x 14 days q3w x 8 cycles Oxaliplatin (Eloxatin) 130 mg/m 2 iv over 2 hrs d1 q3w x 8 cycles Cisplatin 80mg/m2 iv over 4hrs d1 q3w x 8 cycles UFUR 1# po bid CCRT Initial 5-FU 425 mg/m 2 /d iv & Leucovorin 20 mg/m 2 /d iv, d1-5 處方內 容 One month later 5-FU 400 mg/m 2 /d iv & Leucovorin 20 mg/m 2 /d iv, d1-4 and last 3 days of RT Radiotherapy 1.8 Gy/d to 45 Gy One month after completion of RT 5-FU 425 mg/m 2 /d iv, d1-5, q4w x 2 cycles Leucovorin 20 mg/m 2 /d iv, d1-5, q4w x 2 cycles Target therapy 處方內 容 HER2 positive Trastuzumab 8mg/kg iv on Day 1 of cycle 1,then Trastuzumab 6mg/kg iv every 21days Capecitabine 1000mg/m2 po bid on Day 1-14 every 21days or FU 800mg/m2 iv continue infection on Day 1-5 every 21days Cisplatin 80mg/m2 iv on Day1 every 21days 8

9 Breast Cancer Chemotherapy Regimen Neoadjuvant or Adjuvant Regimen 1:FEC:every 3wks for 6 cycles 5-Fluorouracil (5-FU):500 mg/ m2 Epirubicin:75 mg/ m2 Cyclophasphamide:500 mg/ m2 Regimen 2:FEC+ Docetaxel:every 3wks for aa 3 or 4 cycles total 6 or 8 cycles 5-Fluorouracil (5-FU):500mg/ m2 (or no) Epirubicin:75/90mg/ m2 Cyclophasphamide:500mg/ m2 Docetaxel:75/100 mg /m 2 Regimen 3:FLC:every 3wks for 6 cycles 5-Fluorouracil (5-FU):500mg/ m2 Lipo-Dox:30mg/ m2 Cyclophasphamide:500mg/ m2 處方內容 Regimen 4:FLC+ Docetaxel:every 3wks for aa 3 or 4 cycles total 6 or 8 cycles 5-Fluorouracil (5-FU):500mg/ m2 Lipo-Dox:30mg/ m2 Cyclophasphamide:500mg/ m2 Docetaxel 75 mg / m 2 Regimen 5:TEC:every 3wks for 6 cycles Taxotere:75mg/ m2 Epirubicin:75mg/ m2 Cyclophasphamide:500 mg/ m2 Regimen 6:AC:every 3wks Epirubicin:75mg/ m2 Cyclophasphamide:600mg/ m2 Regimen 7:T:every 3wks Taxotere75mg/ m2標靶治療 Herceptin 備註 : loading dose 8mg/kg, 之後才會第二次 : 如下列劑量 處方內容 Herceptin 6MG/KG, Q21d,18cycles 9

10 Bladder Cancer Chemotherapy Regimen 治療方法 Neoadjuvant or Adjuvant Systemic Regimen1:(Ccr >90: 100% dose; 70-90: 70% dose; 50-70:50% dose) Gemcitabine 1000mg/m 2 ; Cisplatin 70mg/m 2 Regimen2: (Ccr<50) Gemcitabine 1000mg/m 2 ; Carboplatin 300mg/m 2 Regimen3: ( C Cr >90: 100% dose; 70-90: 70% dose; 50-70:50% dose) MTX 30mg/m 2 ; Vinblastin 3mg/m 2 ; Epirubicin 30mg/m 2 ; Cisplatin 70mg/m 2 處方內容 Regimen4: (Ccr<50) MTX 30mg/m 2 ; Vinblastin 3mg/m 2 ; Epirubicin 30mg/m 2 ; Carboplatin 300mg/m 2 intravesical Regimen1: Epirubicin 30-50mg qw*8cycles Regimen2: Mitomycin 30mg qw*8cycles 10

11 Prostate Cancer Chemotherapy Regimen CRPC Case 適用 (castration resistance prostate cancer) 處方內容 Systemic Regimen1: Taxotere 70mg/m 2 + Prednisolone 1# bid 5days/ 21~ Q28d,6~8 course 11

12 藥品規格 商品名 學名 劑量 5-Fluorouracil (5-FU) 5-Fluorouracil 500mg/10mL/Vial 1g/20 ml/vial Abiplatin Cisplatin 50mg/ 100ml/Bot Alimta Pemetrexed 500mg/Vial Avastin Bevacizumab 100mg/ 4mL/ Vial Campto Irinotecan 100mg/5ml/Vial Eloxatin Oxaliplatin 50 mg/10ml/vial Emthexate Methotrexate (M.T.X) 50mg/2ml/Vial Eposin Etoposide(VP-16) 100mg/5ml/ Vial Gemzar Gemcitabine 200mg/Vial Genataxyl Paclitaxel 30mg/5ml/Vial Herceptin Trastuzumab 440mg/Vial Kemocarb Carboplatin 150mg/15ml/Vial Lipo-Dox Liposomal Doxorubicin 20mg/10mL/Vial Mitomycin Mitomycin C ( M.M.C.) 2mg/Vial Navelbine Vinorelbine tartrate 50mg/5ml/Vial Pharmorubicin Epirubicin 10mg/Vial Syklofosfamide Cyclophosphamide 500mg/Vial 200mg/Vial Taxotere (20mg) Docetaxel (20mg) 20mg/0.5ml/Vial Taxotere (80mg) Docetaxel (80mg) 80mg/2ml/Vial 12

13 劑量調整 5-Fluorouracil (5-FU) 5-Fluorouracil 老年人 : 參考成人劑量 肝臟功能異常 : 美國食品和藥物管理局核准的劑量不包含特殊的劑量調整指引, 但指出, 必須極其小心使用於肝臟損傷的患者 下面的指引也被作為參考 : Floyd(2006): 膽紅素 >5 mg/dl 避免使用 Koren(1992): 肝臟損傷 ( 程度未明確說明 ): 先給予 <50% 的劑量, 如果毒性未發生可增加劑量 腎臟功能異常 : 美國食品和藥物管理局核准的劑量不包含特殊的劑量調整指導方針, 但指出, 必須極其小心使用於腎臟損傷的患者 血液透析 :Aronoff (2007): 建議 Clcr<50 ml/minute 的成年患者不需要調整劑量, 已接受血液透析的患者僅應該給予 50% 的劑量 Abiplatin Cisplatin 老年人 : 參考成人劑量 肝臟功能異常 : 無相關資料 腎臟功能異常 : 依據廠商建議腎功能不佳者不建議給藥. 直到腎功能回復至 serum creatinine 小於 1.5mg/dl 或 BUN 小於 25mg/dl 才可以再給藥. FDA 並無提供腎功能不佳的建議劑量 下列治療指引為專家的臨床治療建議劑量 :.Aronoff, 2007 Cl cr (ml/min) 劑量 血液透析 : 血液透析會清除部分劑量 75 % < 10 給予正常劑量的 50 % 已接受血液透析患者血液透析後給予正常劑量的 50 % 膜腹透析 (CAPD) 患者給予正常劑量的 50 % 連續性腎替代治療 (CRRT) 患者給予正常劑量的 75 % 血液學異常 : 嗜中性白血球減少症和 / 或血小板減少症 : 1.febrile neutropenia 或長期性嗜中性白血球減少症或是中性白血球減少症引起的感染症且使用 (G-CSF) 治療的病患,cisplatin 合併 docetaxel 治療時需降低 docetaxe 的劑量由 75mg mg/m 2 調降至 60mg/m 2 2. 伴隨有嗜中性白血球降低引起的併發症發生時,cisplatin 合併 docetaxel 治療, 需降低 docetaxe 的劑量由 60mg mg/m 2 調降至 45mg/m 2 3.grade 4 的血小板低下症,cisplatin 合併 docetaxel 治療時, 需降低 docetaxe 的劑量由 75mg mg/m 2 調降至 60mg/m 2 4. 停用 docetaxel, 直到中性粒細胞 >1500 cells/cubic millmeter (mm 3 ) 和血小板 >100000cell/mm 3 5. 若毒性再度發生則須停用 docetaxel 腎功能異常是此藥劑量限制毒性 13

14 Alimta Pemetrexed 肝臟功能異常 : 3 級 ( 倍 ULN) 或 4 級 (>20 倍 ULN) 轉胺酶上升 : 減少 pemetrexed 75% 的劑量 腎臟功能異常 : CCr 45 <80ml/minute 同時有使用 NSAID: 要小心使用 CCr 45 ml/minute: 不需調整劑量 CCr< 45 ml/minute: 無劑量調整之研究證據, 廠商建議停用 毒性劑量的調整 : 血液學毒性 : Nadir ANC <500/mm 3 及 nadir platelet 50000/mm 3 : 減少 pemetrexed 75 % 的劑量 Nadir platelet 50000/mm 3 沒有出血 : 減少 pemetrexed 75% 的劑量 Nadir platelet < 50000/mm 3 有出血 : 減少 pemetrexed 50% 的劑量 非血液學毒性 3 級 ( 不包括神經毒性 ): 停止治療直到恢復正常 ; 再開始治療如下 : 3 或 4 級毒性 ( 不包括黏膜炎 ): 減少 pemetrexed 75% 的劑量 3 或 4 級腹瀉或任何需要住院的腹瀉 : 減少 pemetrexed 75% 的劑量 3 或 4 級黏膜炎 : 減少 pemetrexed 50% 的劑量 ( 維持原 cisplatin 的量 ) 神經毒性 : 0-1 級 : 維持原 pemetrexed 的劑量 ( 及 cisplatin) 2 級 : 維持原 pemetrexed 的劑量, 減少 cisplatin 50% 的劑量 Avastin Bevacizumab 老年人 : 參考成人劑量 肝臟功能異常 : 目前尚無 Avastin 用在肝功能障礙的患者的安全性及療效性 腎臟功能異常 : 目前尚無 Avastin 用在肝功能障礙的患者的安全性及療效性 其他 : 1. 使用 Avastin 治療的病人有較高出血的危險性, 特別是與腫瘤相關的出血 在 Avastin 治療期間出現 3 級或 4 級出血的患者應永久停用 Avastin 2. 患者在使用 Avastin 時, 發生胃腸穿孔的危險性較高 發生胃腸穿孔的患者應永久停用 Avastin 3. 以 Avastin 治療之患者的高血壓發生率較高 臨床安全性數據顯示, 高血壓發生率可能與劑量有關 在開始給予 Avastin 治療前, 應適當控制已存在之高血壓 若發生高血壓危象或高血壓性腦病變, 應永久停用 Avastin 14

15 Campto Irinotecan 老年人 : 參考成人劑量 肝臟功能異常 : 1. 對於轉移性肝腫瘤或正常肝功能患者建議並不須更改劑量 2. 臨床醫師建議 :Bilirubin1.5-3 mg/dl irinotecan 劑量調整 75%(Floyd,2006) 腎臟功能異常 : 腎功能不全患者尚無相關使用評估 ; 不建議用於洗腎患者. 血液學異常 : 1. 若患者顆粒性白血球 1500/mm 3 血小板 100,000/mm 3 且因治療而產生腹瀉完全緩解, 即可進行新療程. 2. 依據患者對於治療的耐受性, 劑量可隨之增加 mg/m 2 3. 療程需延緩 1-2 週以利治療產生的毒性回復 ; 若患者於 2 週的延遲治療並未回復, 則考慮停用 irinotecan Eloxatin Oxaliplatin 老年人 : 老年患者不需調整劑量 肝臟功能異常 : Oxaliplatin 尚未對重度肝力能不良的病人進行研究. 對於肝功能異常的病人使用 Oxaliplatin 後並未觀察到有急性肝毒性加劇的現象, 在臨床試驗時對於肝功能異常的病患並 無調整劑量. 腎臟功能異常 : 血液學異常 : Clcr ( ml/min ) 劑量 輕度至中度腎功能不全 不需調整 重度腎功能不全 < 20 停用 若產生 3 或 4 級胃腸毒性 4 級啫中性白血球減少症 3 或 4 級血小板減少症 : 1. 第三期直腸癌 : 減少 Oxaliplatin 劑量為 75 mg/m 2, 延緩下次投與劑量直至啫中性白血球 1500/mm 3 及血小板 75,000/mm 3 2. 轉移性結腸直腸癌 : 減少 Oxaliplatin 劑量為 65 mg/m 2, 延緩下次投與劑量直至啫中性白血球 1500/mm 3 及血小板 75,000/mm 3 Emthexate Methotrexate/ M.T.X 老年人 : 參考個別之治療計畫 ; 依腎功能調整劑量 肝臟功能異常 : FDA 尚未核准劑量調整指引 一些臨床醫師使用以下方式進行劑量調整 (Floyd, 2006): 1. 膽紅素 mg/dl 或 GPT/GOT > 3 倍正常值上限 : 應調整劑量為原本之 75% 2. 膽紅素 > 5mg/dL: 避免使用 15

16 腎臟功能異常 :Aronoff, 2007: 肌酸酐清除率 (ml/min) 劑量調整 10~50 正常劑量的 50% < 10 正常劑量的 30 % 血液透析 正常劑量的 50 % 連續性腎臟替代療法 (CRRT) 正常劑量的 50 % Eposin Etoposide(VP-16) 肝功能異常及老年人無劑量調整之研究證據, 但肝功能異常使用須小心 腎臟功能異常 : Ccr:10~50ml/min 給予 75% 劑量 Ccr<10ml/min 給予 50% 劑量骨髓抑制是此藥主要劑量限制毒性 Gemzar Gemcitabine 老年人 : 參照成人劑量 肝臟功能異常 : FDA 核準說明中, 並無包含劑量調整準則, 需小心使用 Gemcitabine 目前無使用於肝功能不全患者的相關研究, 因此目前無明確的劑量調整準則 臨床上 (Floyd, 2006) 可遵從的準則建議當 Serum bilirubin >1.6 mg/dl 時, 由 800 mg/m 2 開始使用 腎臟功能異常 : FDA 核準說明並無包含劑量調整準則, 需小心使用使用 Gemcitabine 目前無使用於腎功能不全者的相關研究, 因此目前無明確的劑量調整準則 血液學異常 : 治療時應每隔一週檢查 CBC&DC, 若出現血液毒性, 需要時可依下列準則降低劑量或停藥 ANC(ul) 血小板 (ul) 總劑量之白分比 >1000 且 > % 或 % <500 或 <50000 停藥 骨髓抑制是此藥劑量限制毒性 16

17 Genataxyl Paclitaxel 過敏反應需以 corticosteroid diphenhydramine H2 blocker 於給藥前給予作為預防性給藥 廠商建議 ANC 低於 1500/µL 的病人不要給藥 發生嚴重的嗜中性白血球減少症或神經病變必須 減量 20% 老年人 : 參考成人劑量 肝臟功能異常 : 依據 FDA 建議, 在肝功能正常患者第一次療程中, 給藥劑量為 175 mg/m 2, 輸注大於 3 小時 故肝功能異常患者, 其劑量調整如下 : 輸注 3 小時 GPT/GOT Bilirubin 建議劑量 <10 倍 ULN 和 1.25 倍 ULN 175 mg/m 2 <10 倍 ULN 和 倍 ULN 135 mg/m 2 <10 倍 ULN 和 倍 ULN 90 mg/m 2 10 倍 ULN 或 >5 倍 ULN 避免使用 腎臟功能異常 : 關於腎功能異常的劑量調整,FDA 目前無相關文獻建議 而 2007 年 Arnoff 對於 Cl cr < 50 ml/minute 患者, 也無劑量調整資料 劑量限制毒性包括骨髓抑制骨髓抑制 過敏反應過敏反應 心率不整心率不整 神經病變神經病變 Herceptin Trastuzumab 老年人 : 參考成人劑量肝臟功能異常 : 無劑量調整之需求腎臟功能異常 : 無劑量調整之需求血液學異常 : 依心臟毒性之劑量調整 : LVEF 值降低 16%( 由基礎值至正常值上限間 ) 或 LVEF 值在正常值上限之下或 LVEF 值降低 10%( 基礎值 ) 時, 暫停治療 4 週, 且每 4 週追蹤一次 LVEF 值 若 LVEF 值在 4-8 週後恢復至正常值內且 LVEF 值降低 15%( 由基礎值至正常值上限間 ), 得以繼續治療 若 LVEF 值在停用 8 週以上仍未恢復至正常值或治療期間出現 3 個以上心肌病導致治療中斷情形時, 應繼續停用 Kemocarb Carpoplatin 老年人 : 老年人劑量的調整根據 Calvert 公式老年人建議劑量計算公式以 GFR 的預估值來計算以病人 GFR (in ml/minute) 及 target AUC (in mg/ml per minute) 為基礎計算, 劑量是 mg; 非 mg/m 2 Calvert Formula: total dose (mg) = target AUC (in mg/ml per min) [GFR (in ml/min) + 25]target AUC of 5 (range: 4 6) mg/ml per minute: 為之前已經使用過化療藥物治療病人, 今需使用 carboplatin 單一治療者最常被建議使用的劑量範圍 17

18 肝臟功能異常 : 僅極少部分由肝臟代謝, 因此肝功能不佳病患不須做調整劑量, 且目前無劑量調整準則 腎臟功能異常 : 腎功能異常劑量調整建議以 Calvert 公式之 GFR 的預測值來計算 ; 當病人 Clcr <60 ml/minute 時應降低劑量使用 ;FDA 核准建議劑量調整準則 : Baseline Clcr Initial Dose 60 ml/min 360 mg/m 2 ; 之後劑量依骨髓毒性作調整 ml/min 250 mg/m 2 ; 之後劑量依骨髓毒性作調整 ml/min 200 mg/m 2 ; 之後劑量依骨髓毒性作調整 當病人 Clcr <15 ml/minute, 在劑量調整上有太多限制, 並無準則可使用 特殊病人之劑量調整 : 腎功能異常劑量調整 已接受血液透析病患 給予建議劑量的 50% 腹膜透析病患 (CAPD) 給予建議劑量的 25% 連續性腎替代性治療 (CRRT) 給予 200 mg/m 2 血液學異常 : 血小板 <50,000 cells/mm 3 或絕對嗜中性白血球數 <500 cells/mm 3 : 給予建議劑量的 75% 骨髓抑制是此藥主要劑量限制毒性 Lipo-Dox Liposomal Doxorubicin 老年人 : 參照成人劑量 微脂體藥物包覆劑型與傳統 doxorubicin hydrochloride 劑型不可直接進行 劑量轉換 肝臟功能異常 : 微脂體藥物包覆劑型與傳統 doxorubicin hydrochloride 劑型不可直接進行劑量轉換 肝功能指標 劑量調整 GPT/GOT 其 ULN 的 2-3 倍 建議劑量的 75% GPT/GOT 其 ULN 的 3 倍以上或 Bilirubin:1.2-3mg/dL 建議劑量的 50% Bilirubin 3.1-5mg/dL 建議劑量的 25% Bilirubin >5 mg/dl 不建議使用 腎臟功能異常 :Doxorubicin 為肝臟代謝 膽汁排除, 故不需劑量調整之需求 血液學異常 : 血液學檢查異常劑量調整 等級 嗜中性白血球 血小板 劑量調整 (ANC) 第一級 , ,000 不需調整劑量 第二級 1000 < ,000 <75,000 待 ANC 1500 且血小板 75,000 時, 可繼續治療, 不需調整劑量 18

19 第三級 ,000 50,000 待 ANC 1500 且血小板 75,000 時, 可繼續治療, 不需調整劑量 第四級 <500 <25,000 待 ANC 1500 並且血小板 75,000 時, 降低 25% 劑量或不調整劑量 手足症候群 : 等級 劑量調整 第一級 若病患曾經歷第 3 級或 4 級的毒性, 延遲給藥 2 星期, 並依之前劑量降低 25% 的劑量, 以相同投藥間隔給予 延遲給藥 2 星期或直到症狀緩解成第 0-1 級 若 2 星期之內緩解成第 0-1 級且之前無第 3-4 級的毒性時, 依之前劑量和投 藥間隔給予 第二級 若 2 星期之內緩解成第 0-1 級且之前有第 3-4 級的毒性時, 依之前劑量降低 25% 並以相同投藥間隔給予 若 2 星期後症狀未獲得緩解則應停藥 延遲給藥 2 星期或者直到症狀緩解成第 0-1 級, 依之前劑量降低 25% 並以相同 第三級 投藥間隔給予 若 2 星期後症狀未獲得緩解則應停藥 延遲給藥 2 星期或者直到症狀緩解成第 0-1 級, 依之前劑量降低 25% 並以相同 第四級 投藥間隔給予 若 2 星期後症狀未獲得緩解則應停藥 Mitomycin C M.M.C. 老年人 : 參考成人劑量 因高齡者通常生理機能較低, 骨髓功能更易受抑制, 且抑制期可能延長, 也容易發生腎功能障礙, 所以投藥時必須小心觀察病人情況, 特別注意劑量及投與間隔 肝臟功能異常 : 依據廠商建議須經常做臨床肝功能檢查, 以便隨時監控病情, 如發生有異常時, 須做減量或停藥等適當處理 另長期使用時, 可能增強, 也可能會延長, 因此須慎重投藥 腎臟功能異常 : 依據廠商建議須經常做臨床腎功能檢查, 以便隨時監控病情, 如發生有異常時, 須做減量或停藥等適當處理 另長期使用時, 可能增強, 也可能會延長, 因此須慎重投藥 血液學檢查 : 可能會引起骨髓造血機能抑制, 如全部血球減少 白血球減少 嗜中性白血球減少 血小板減少 出血和貧血, 依據廠商建議須經常做臨床血液檢查, 以便隨時監控病情, 如發生有異常時, 須做減量或停藥等適當處理 另長期使用時, 可能增強, 也可能會延長, 因此須慎重投藥 列出可能發生的, 病人應接受密切的觀察, 如有異狀應做適當處置, 如降低劑量或終止用藥, 如下表 : 19

20 5% 5% > 發生率不明 0.1% 腎臟 蛋白尿 血尿 水腫 高血壓 肝臟腸胃系統 厭食 噁心 / 嘔吐 口炎 腹瀉 過敏 皮疹 泌尿系統 ( 膀胱灌洗 ) 膀胱炎 血尿 膀胱萎縮 其他 身體不適 禿髮 骨髓抑制是此藥主要劑量限制毒性 Navelbine Vinorelbine 老年人 : 參考成人劑量 肝臟功能異常 : FDA 核准之指引如下 : 肝功能不全者給予 Vinorelbine 治療時, 應小心謹慎 若使用 Vinorelbine 治療期間產生高膽紅素血症, 應視其膽紅素血中濃度而調整劑量, 劑量調整方式 如下 : Total Bilirubin (mg/dl) 劑量調整 2.0 正常劑量的 100 % 2.1 to 3.0 正常劑量的 50 % >3.0 正常劑量的 25 % 腎臟功能異常 : 不需調整劑量 血液學檢查 : 治療當天顆粒性白血球計數 (cells/mm 3 ) 劑量調整 1,500 正常劑量的 100 % 1,000 to 1,499 正常劑量的 50 % <1000 暫停給藥治療期間若病人因顆粒性白血球低下 (granulocytopenic) 而發燒 產生敗血症或因顆粒 性白血球低下而連續暫停兩次劑量之治療, 隨後的 vinorelbine 治療劑量調整如下 : 治療當天顆粒性白血球計數 (cells/mm 3 ) 劑量調整 1,500 正常劑量的 75% 1,000 to 1,499 正常劑量的 37.5% <1,000 暫停給藥 白血球低下是此藥主要劑量限制毒性 20

21 Pharmorubicin Epirubicin 老年人 : 老年女性患者其 Epirubicin 的血漿清除率減少 35% 然而對降低起始劑量的方面並沒有 具體的建議, 但特別應注意老年患者的毒性監督和劑量調整 ( 尤其是 70 歲以上女性 ) 肝臟功能異常 : FDA 核准的建議如下列準則 ( 根據臨床試驗資料 ): Bilirubin/GOT 劑量調整 1.2-3mg/dl 或 UNL 的 2-4 倍建議起始劑量的 50% 大於 3mg/dl 或 UNL 的 4 倍建議起始劑量的 25% 嚴重肝損害 腎臟功能異常 禁用 FDA 核准建議 : 重度腎功能損害 ( 血清肌酐酸 >5mg/dl) 的病人, 應考慮較低的劑量 Aronoff( 2007 ) 建議 Cl cr <50 ml/minute. 不作劑量調整需要 血液學異常 : 1. 當病患血小板計數是在 <50,000/ mm 3, ANC <250/ mm 3 或有 neutropenic fever, 應該減少隨後週期的第一天藥量到目前劑量的 75% 下次療程的第 1 天化療, 應等 到病患血小板數大於或等於 100,000/ mm 3 或 ANC 大於或等於 1500/ mm 3, 才執行 2. 在病患接受 Epirubicin 治療的第 1 天及第 8 天中, 假如病患血小板數是在 75,000 to 100,000/ mm 3 及 ANC 在 1000 to 1499/ mm 3, 則第 8 天的劑量只要第一天的 75% 即可 3. 若病患血小板數小於 75,000/ mm 3 或 ANC 小於 1000/ mm 3 時, 則第 8 天劑量可省略不做 骨髓抑制是此藥短期劑量限制毒性 心臟損傷是長期劑量限制毒性, 最高累積劑量為 900mg/ m2 Syklofosfamide Cyclophosphamide 老年人 : 針對個人情況做調整, 建議開始及維持劑量 :1-2mg/kg/day; 依照 renal clearance 調整 肝臟功能異常 : Cyclophosphamide 的藥物動力學在肝功能不良的病人並沒有明顯的改變 FDA 核准的建議劑量並不包括肝功能劑量的調整準則. 下列的準則曾被一些臨床醫師採用 (Floyd, 2006): Serum bilirubin mg/dl 或 GPT/GOT >3 倍 ULN: 使用 75% 的劑量 Serum bilirubin >5 mg/ml: 避免使用 腎臟功能異常 : FDA 所核准的建議劑量沒有足夠的證據去建議在腎功能的劑量調整. 下列的準則曾被一些臨床醫師採用 (Aronoff, 2007): 兒童或成人 :Cl cr <10 ml/minute: 使用正常劑量的 75% 血液透析的作用 : 中度透析 (20% to 50%): 透析後給予 50% 的劑量 連續可活動性腹膜透析 (CAPD) : 給予正常劑量的 75% 連續性腎臟替代療法 (CRRT): 給予正常劑量的 100% 骨髓抑制和出血性膀胱炎是此藥劑量限制毒性, 而骨髓抑制是最主要的 21

22 Taxotere Docetaxel 所有的病人必須於給藥前給予皮質類固醇作為預防性給藥, 以降低過敏反應和體液滯留的嚴重度 老年人 : 參照成人劑量 肝臟功能異常 : 1. 當 Total bilirubin> 正常值上限或 GOT/GPT>1.5 倍且 Alkaline phosphatase(alp >2.5 倍正常值上限時, 不建議使用 docetaxel 2. 其它文獻建議 Floyd, 2006 : GOT/GPT>ULN 的 倍時, 將劑量調整為正常劑量的 75% GOT/GPT>ULN 的 6 倍時, 需依照臨床上的評估 腎臟功能異常 :Docetaxel 只有少部分由腎排除, 不需調整劑量 血液學異常 : 依毒性調整劑量 : 1.Docetaxel 引起的毒性包含 febrile neutropenia,neutrophils 持續一星期以上低於 500 cells/mm 3, 嚴重或蓄積性皮膚反應 2. 乳癌患者, 若起始劑量為 100 mg/m 2, 其血液學檢查異常時, 應將劑量降低為 75 mg/m 2 若持續, 應將劑量降至 55 mg/m 2 或停用 若末稍神經病變大於 3 級時應停用 3. neutrophils 小於 1500 cells/mm 3 的患者不建議使用 docetaxel 劑量限制毒性包括骨髓抑制骨髓抑制 過敏反應過敏反應 肝損傷肝損傷 22

23 Gemzar >10% 常見 Peripheral edema (20%), edema (13%), Pain (10% to 48%), fever (30% to 41%), somnolence (5% to 11%), Rash (24% to 30%), alopecia (15% to 18%), pruritus (13%), Nausea/vomiting (64% to 71%; grades 3/4: 1% to 13%), constipation (10% to 31%), diarrhea (19% to 30%), stomatitis (10% to 14%),Anemia (65% to 73%; grade 4: 1% to 3%), leukopenia (62% to 71%; grade 4: 1%), neutropenia (61% to 63%; grade 4: 6% to 7%), thrombocytopenia (24% to 47%; grade 4: 1%), hemorrhage (4% to 17%; grades 3/4: <1% to 2%); myelosuppression is the dose-limiting toxicity, Transaminases increased (67% to 78%; grades 3/4: 1% to 12%), alkaline phosphatase increased (55% to 77%; grades 3/4: 2% to 16%), bilirubin increased (13% to 26%; grades 3/4: <1% to 6%), Proteinuria (10% to 45%; grades 3/4: <1%), hematuria (13% to 35%; grades 3/4: <1%), BUN increased (8% to 16%; grades 3/4: 0%), Dyspnea (6% to 23%), Flu-like syndrome (19%), infection (8% to 16%; grades 3/4: <1% to 2%) 1% to 10% Injection site reactions (4%), Paresthesia (2% to 10%), Creatinine increased (2% to 8%), Bronchospasm (<2%) <1% Adult respiratory distress syndrome, anaphylactoid reaction, anorexia, arrhythmias, bullous skin eruptions, cellulitis, cerebrovascular accident, CHF, chills, cough, desquamation, diaphoresis, gangrene, GGT increased, headache, hemolytic uremic syndrome (HUS), hepatotoxic reaction (rare), hypertension, insomnia, interstitial pneumonitis, liver failure, malaise, MI, peripheral vasculitis, petechiae, pulmonary edema, pulmonary fibrosis, radiation recall, renal failure, respiratory failure, rhinitis, sepsis, supraventricular arrhythmia, weakness 5-Fluorouracil (5-Fluorouracil (5-FU)) Angina, myocardial ischemia, nail changes,acute cerebellar syndrome, confusion, disorientation, euphoria, headache, nystagmus, Alopecia, dermatitis, dry skin, fissuring, palmar-plantar erythrodysesthesia syndrome, pruritic maculopapular rash, photosensitivity, vein pigmentations, Anorexia, bleeding, diarrhea, esophagopharyngitis, nausea, sloughing, stomatitis, ulceration, vomiting, Agranulocytosis, anemia, leukopenia, pancytopenia, thrombocytopenia Myelosuppression: (Onset: 7-10 days;nadir: 9-14 days;recovery: days), Thrombophlebitis,Lacrimation, lacrimal duct stenosis, photophobia, visual changes, Epistaxis, Anaphylaxis, generalized allergic reactions, nail loss Epirubicin >10% Lethargy (1% to 46%),Alopecia (69% to 96%), Amenorrhea (69% to 72%), hot flashes (5% to 39%), Nausea/vomiting (83% to 92%; grades 3/4: 22% to 25%), mucositis (9% to 59%; grades 3/4: 9%), diarrhea (7% to 25%), Leukopenia (50% to 80%; grades 3/4: 2% to 59%), neutropenia (54% to 80%; grades 3/4: 11% to 67%; nadir: days; recovery: 21 days), anemia (13% to 72%; grades 3/4: 6%), thrombocytopenia (5% to 49%; grades 3/4: 5%), Injection site reactions (3% to 20%; grades 3/4: <1%), Conjunctivitis (1% to 15%), Infection (15% to 22%; grades 3/4: 2%) 23

24 1% to 10% LVEF decreased (asymptomatic; delayed: 1% to 2%), HF (0.4% to 1.5%), Fever (1% to 5%), Rash (1% to 9%), skin changes (1% to 5%), Anorexia (2% to 3%), Neutropenic fever (grades 3/4: 6%) 副作 <1% Abdominal pain, acute lymphoid leukemia (ALL), acute myelogenous leukemia (AML), anaphylaxis, ascites, atrioventricular block, bradycardia, bundle-branch block, cardiomyopathy, chills, dehydration, dyspnea, ECG abnormalities, esophagitis, hepatomegaly, hyperpigmentation (oral mucosa, nails, skin), hypersensitivity, myelodysplastic syndrome, photosensitivity, premature menopause, premature ventricular contractions, pulmonary edema, pulmonary embolism, radiation recall, shock, sinus tachycardia, stomatitis, ST-T wave changes (nonspecific), tachyarrhythmias, thromboembolism, thrombophlebitis, transaminases increased, urticaria, ventricular tachycardia Cyclophosphamide >10% Alopecia (40% to 60%), May cause sterility, Nausea and vomiting, anorexia, diarrhea, mucositis, stomatitis, acute hemorrhagic cystitis (7% to 40%), Thrombocytopenia and anemia are less common than leukopenia (ALL)Onset: 7 days;nadir: days ;Recovery: 21 days 1% to 10% Facial flushing, Headache, Skin rash, Nasal congestion occurs when I.V. doses are administered too rapidly; patients experience runny eyes, rhinorrhea, sinus congestion, and sneezing during or immediately after the infusion. <1% High-dose therapy may cause cardiac dysfunction manifested as CHF; cardiac necrosis or hemorrhagic myocarditis has occurred rarely, but may be fatal. Interstitial pneumonitis and pulmonary fibrosis are occasionally seen with high doses. Cyclophosphamide may also potentiate the cardiac toxicity of anthracyclines. Other adverse reactions include anaphylactic reactions, darkening of skin/fingernails, dizziness, hemorrhagic colitis, hemorrhagic ureteritis, hepatotoxicity, hyperuricemia, hypokalemia, jaundice, malaise, neutrophilic eccrine hidradenitis, radiation recall, renal tubular necrosis, secondary malignancy (eg, bladder carcinoma), SIADH, Stevens-Johnson syndrome, toxic epidermal necrolysis, weakness. Taxotere >10% Fluid retention (13% to 60%; dose dependent),neurosensory events (20% to 58%; including neuropathy), fever (31% to 35%), neuromotor events (16%),Alopecia (56% to 76%), cutaneous events (20% to 48%), nail disorder (11% to 41%),Stomatitis (19% to 53%; severe 1% to 8%), diarrhea (23% to 43%; severe: 5% to 6%), nausea (34% to 42%), vomiting (22% to 23%), Neutropenia (84% to 99%; grade 4: 75% to 86%; onset: 4-7 days, nadir: 5-9 days, recovery: 21 days; dose dependent), leukopenia (84% to 99%; grade 4: 32% to 44%), anemia (65% to 94%; dose dependent; grades 3/4: 8% to 9%), thrombocytopenia (8% to 14%; grade 4: 1%; dose dependent), febrile neutropenia (6% to 12%; dose dependent), Transaminases increased (4% to 19%), Weakness (53% to 66%; severe 13% to 18%), myalgia (3% to 23%), Pulmonary events (41%), Infection (1% to 34%; dose dependent), hypersensitivity (1% to 21%; with premedication 15%) 24

25 1% to 10% Left ventricular ejection fraction decreased (prostate cancer: 10%; metastatic breast cancer: 8%), hypotension (3%), Rash/erythema (2%), Taste perversion (6%), Bilirubin increased (9%), alkaline phosphatase increased (4% to 7%), Infusion-site reactions (4%, including hyperpigmentation, inflammation, redness, dryness, phlebitis, extravasation, swelling of the vein), Arthralgia (3% to 9%), Epiphora associated with canalicular stenosis ( 77% with weekly administration; 1% with every 3-week administration) <1% Acute myeloid leukemia (AML), acute respiratory distress syndrome (ARDS), anaphylactic shock, angina, ascites, atrial fibrillation, atrial flutter, bleeding episodes, bronchospasm, cardiac tamponade, chest pain, chest tightness, colitis, conjunctivitis, constipation, cutaneous lupus erythematosus, deep vein thrombosis, dehydration, disseminated intravascular coagulation (DIC), drug fever, duodenal ulcer, dyspnea, dysrhythmia, ECG abnormalities, erythema multiforme, esophagitis, gastrointestinal hemorrhage, gastrointestinal obstruction, gastrointestinal perforation, hand and foot syndrome, hearing loss, heart failure, hepatitis, hypertension, ileus, interstitial pneumonia, ischemic colitis, lacrimal duct obstruction, loss of consciousness (transient), MI, multiorgan failure, myelodysplastic syndrome, neutropenic enterocolitis, ototoxicity, pleural effusion, pruritus, pulmonary edema, pulmonary embolism, pulmonary fibrosis, radiation pneumonitis, radiation recall, renal insufficiency, seizure, sepsis, sinus tachycardia, Stevens-Johnson syndrome, syncope, toxic epidermal necrolysis, tachycardia, thrombophlebitis, unstable angina, visual disturbances (transient) lipo-dox >10% Peripheral edema ( 11%), Fever (8% to 21%), headache ( 11%), pain ( 21%), Palmar-plantar erythrodysesthesia/hand-foot syndrome ( 51% in ovarian cancer [grades 3/4: 24%]; 3% in Kaposi's sarcoma), rash ( 29% in ovarian cancer, 5% in Kaposi's sarcoma), alopecia (9% to 19%), Nausea (17% to 46%), stomatitis (5% to 41%), vomiting (8% to 33%), constipation ( 30%), diarrhea (5% to 21%), anorexia ( 20%), mucositis ( 14%), dyspepsia ( 12%), intestinal obstruction ( 11%), Myelosuppression (onset: 7 days; nadir: days; recovery: days), thrombocytopenia (13% to 65%; grades 3/4: 1%), neutropenia (12% to 62%; grade 4: 4%), leukopenia (36%), nemia (6% to 74%; grade 4: <1%), Weakness (7% to 40%), back pain ( 12%), Pharyngitis ( 16%), dyspnea ( 15%), Infection ( 12%) 1% to 10% Cardiac arrest, chest pain, deep thrombophlebitis, edema, hypotension, pallor, tachycardia, vasodilation, Agitation, anxiety, chills, confusion, depression, dizziness, emotional lability, insomnia, somnolence, vertigo, Acne, bruising, dry skin (6%), exfoliative dermatitis, fungal dermatitis, furunculosis, maculopapular rash, pruritus, skin discoloration, vesiculobullous rash, Dehydration, hypercalcemia, hyperglycemia, hypokalemia, hyponatremia, Abdomen enlarged, anorexia, ascites, cachexia, dyspepsia, dysphagia, esophagitis, flatulence, gingivitis, glossitis, ileus, mouth ulceration, oral moniliasis, rectal bleeding, taste perversion, weight loss, xerostomia, Cystitis, dysuria, leukorrhea, pelvic pain, polyuria, urinary incontinence, urinary tract infection, urinary urgency, vaginal bleeding, vaginal moniliasis, Hemolysis, prothrombin time increased, ALT increased, alkaline phosphatase increased, hyperbilirubinemia, Thrombophlebitis, Arthralgia, hypertonia, myalgia, neuralgia, neuritis (peripheral), neuropathy, paresthesia ( 10%), pathological fracture, Conjunctivitis, dry eyes, retinitis, Ear pain, Albuminuria, hematuria, Apnea, cough ( 10%), epistaxis, pleural effusion, 25

26 pneumonia, rhinitis, sinusitis, Allergic reaction; infusion-related reactions (7%; includes bronchospasm, chest tightness, chills, dyspnea, facial edema, flushing, headache, herpes simplex/zoster, hypotension, pruritus); moniliasis, diaphoresis <1% Abscess, acute brain syndrome, abnormal vision, acute myeloid leukemia (secondary), alkaline phosphatase increased, anaphylactic or anaphylactoid reaction, asthma, balanitis, blindness, bone pain, bronchitis, BUN increased, bundle branch block, cardiomegaly, cardiomyopathy, cellulitis, CHF, colitis, creatinine increased, cryptococcosis, diabetes mellitus, erythema multiforme, erythema nodosum, eosinophilia, fecal impaction, flu-like syndrome, gastritis, glucosuria, hemiplegia, hemorrhage, hepatic failure, hepatitis, hepatosplenomegaly, hyperkalemia, hypernatremia, hyperuricemia, hyperventilation, hypoglycemia, hypolipidemia, hypomagnesemia, hypophosphatemia, hypoproteinemia, hypothermia, injection site hemorrhage, injection site pain, jaundice, ketosis, lactic dehydrogenase increased, kidney failure, lymphadenopathy, lymphangitis, migraine, myositis, optic neuritis, palpitation, pancreatitis, pericardial effusion, petechia, pneumothorax, pulmonary embolism, radiation injury, sclerosing cholangitis, seizure, sepsis, skin necrosis, skin ulcer, syncope, Stevens-Johnson syndrome, tenesmus, thromboplastin decreased, thrombosis, tinnitus, toxic epidermal necrolysis, urticaria, visual field defect, ventricular arrhythmia Herceptin >10% LVEF decreased (4% to 22%), Pain (47%), fever (6% to 36%), chills (5% to 32%), headache (10% to 26%), insomnia (14%), dizziness (4% to 13%), Rash (4% to 18%), Nausea (6% to 33%), diarrhea (7% to 25%), vomiting (4% to 23%), abdominal pain (2% to 22%), anorexia (14%), Weakness (4% to 42%), back pain (5% to 22%), Cough (5% to 26%), dyspnea (3% to 22%), rhinitis (2% to 14%), pharyngitis (12%), Infusion reaction (21% to 40%, chills and fever most common; severe: 1%), infection (20%) 1% to 10% Peripheral edema (5% to 10%), edema (8%), HF (2% to 7%; severe: <1%), tachycardia (5%), hypertension (4%), arrhythmia (3%), palpitation (3%), Depression (6%), Acne (2%), nail disorder (2%), pruritus (2%), Constipation (2%), dyspepsia (2%), Urinary tract infection (3% to 5%), Anemia (4%), leukopenia (3%), Paresthesia (2% to 9%), bone pain (3% to 7%), arthralgia (6% to 8%), myalgia (4%), muscle spasm (3%), peripheral neuritis (2%), neuropathy (1%), Sinusitis (2% to 9%), nasopharyngitis (8%), upper respiratory infection (3%), epistaxis (2%), pharyngolaryngeal pain (2%), Flu-like syndrome (2% to 10%), accidental injury (6%), influenza (4%), allergic reaction (3%), herpes simplex (2%) <1% Acute respiratory distress syndrome (ARDS), amblyopia, anaphylaxis, anaphylactoid reaction, angioedema, apnea, ascites, asthma, ataxia, bone necrosis, bronchospasm, cardiac arrest, cardiomyopathy, cellulitis, coagulopathy, colitis, confusion, deafness, esophageal ulcer, gastroenteritis, glomerulonephritis (membraneous, focal and fibrillary), glomerulopathy, glomerulosclerosis, hematemesis, hemorrhage, hemorrhagic cystitis, hepatic failure, hepatitis, herpes zoster, hydrocephalus, hydronephrosis, hypercalcemia, hypersensitivity, hypotension, hypothyroidism, hypoxia, ileus, intestinal obstruction, interstitial pneumonitis, laryngitis, leukemia (acute), lymphangitis, mania, mural thrombosis, myopathy, nephrotic syndrome, neutropenia, oligohydramnios, pancreatitis, pancytopenia, paroxysmal nocturnal dyspnea, pathological fracture, pericardial effusion, pleural effusion, pneumonitis, pneumothorax, pulmonary edema (noncardiogenic), pulmonary fibrosis, pulmonary hypertension, pulmonary infiltrate, pyelonephritis, radiation injury, 26

27 renal failure, respiratory distress, respiratory failure, seizure, sepsis, shock, skin ulcers, stroke, syncope, stomatitis, thyroiditis (autoimmune), vascular thrombosis, ventricular dysfunction, volume overload Methotrexate >10% Acute reaction manifested as severe headache, nuchal rigidity, vomiting, and fever; may be alleviated by reducing the dose, Subacute toxicity: 10% of patients treated with mg/m 2 of I.T. methotrexate may develop this in the second or third week of therapy; consists of motor paralysis of extremities, cranial nerve palsy, seizure, or coma. This has also been seen in pediatric cases receiving very high-dose I.V. methotrexate. Demyelinating encephalopathy: Seen months or years after receiving methotrexate; usually in association with cranial irradiation or other systemic chemotherapy. Reddening of skin, Hyperuricemia, defective oogenesis or spermatogenesis, Ulcerative stomatitis, glossitis, gingivitis, nausea, vomiting, diarrhea, anorexia, intestinal perforation, mucositis (dose dependent; appears in 3-7 days after therapy, resolving within 2 weeks), Leukopenia, myelosuppression (nadir: 7-10 days), thrombocytopenia, Renal failure, azotemia, nephropathy, Pharyngitis 1% to 10% Vasculitis, Dizziness, malaise, encephalopathy, seizure, fever, chills, Alopecia, rash, photosensitivity, depigmentation or hyperpigmentation of skin, Diabetes, Cystitis, Hemorrhage, Cirrhosis and portal fibrosis have been associated with chronic methotrexate therapy; acute elevation of liver enzymes are common after high-dose methotrexate, and usually resolve within 10 days. Arthralgia, Blurred vision. Renal dysfunction: Manifested by an abrupt rise in serum creatinine and BUN and a fall in urine output; more common with high-dose methotrexate, and may be due to precipitation of the drug. Pneumonitis: Associated with fever, cough, and interstitial pulmonary infiltrates; treatment is to withhold methotrexate during the acute reaction; interstitial pneumonitis has been reported to occur with an incidence of 1% in patients with RA (dose mg/week) <1% Acute neurologic syndrome (at high dosages - symptoms include confusion, hemiparesis, transient blindness, and coma); anaphylaxis, alveolitis, cognitive dysfunction (has been reported at low dosage), decreased resistance to infection, erythema multiforme, hepatic failure, leukoencephalopathy (especially following craniospinal irradiation or repeated high-dose therapy), lymphoproliferative disorders, osteonecrosis and soft tissue necrosis (with radiotherapy), pericarditis, plaque erosions (psoriasis), seizure (more frequent in pediatric patients with ALL), Stevens-Johnson syndrome, thromboembolism Cisplatin >10% Peripheral neuropathy is dose- and duration-dependent. Mild alopecia, Nausea and vomiting (76% to 100%), Myelosuppression (25% to 30%; mild with moderate doses, mild-to-moderate with high-dose therapy) : WBC: Mild, Platelets: Mild (onset: 10 days; Nadir: days; Recovery: days), Liver enzymes increased, Nephrotoxicity (acute renal failure and chronic renal insufficiency) Ototoxicity (10% to 30%; manifested as high frequency hearing loss; ototoxicity is especially pronounced in children) 1% to 10% Diarrhea, Tissue irritation 27

28 <1% Anaphylactic reaction, arrhythmias, blurred vision, bradycardia, cerebral blindness, hemolytic anemia, liver enzymes increased, mild alopecia, mouth sores, optic neuritis, papilledema Carboplatin >10% Pain (23%), Hyponatremia (29% to 47%), hypomagnesemia (29% to 43%), hypocalcemia(22% to 31%), hypokalemia (20% to 28%), Vomiting (65% to 81%), abdominal pain (17%), nausea (without vomiting: 10% to 15%), Myelosuppression (dose related and dose limiting; nadir at ~21 days; recovery by ~28 days), anemia (71% to 90%; grades 3/4: 21%), leukopenia (85%; grades 3/4: 15% to 26%), neutropenia (67%; grades 3/4: 16% to 21%), thrombocytopenia (62%; grades 3/4: 25% to 35%), Alkaline phosphatase increased (24% to 37%), AST increased (15% to 19%), Weakness (11%), Creatinine clearance decreased (27%), BUN increased (14% to 22%), Hypersensitivity/ Allergic reaction (2% to 16%) 1% to 10% Neurotoxicity (5%), Alopecia (2% to 3%), Constipation (6%), diarrhea (6%), stomatitis/mucositis (1%), taste dysgeusia (1%), Bleeding (5%), hemorrhagic complications (5%), Bilirubin increased (5%), Peripheral neuropathy (4% to 6%), Visual disturbance (1%), Ototoxicity (1%), Creatinine increased (6% to 10%), Infection (5%) <1% <1% (Limited to important or life-threatening): Anaphylactic reaction, bronchospasm, cardiac failure, cerebrovascular accident, dehydration, embolism, erythema, hemolytic uremic syndrome (HUS), hyper-/hypotension, injection site reactions (pain, redness, swelling), necrosis (associated with extravasation), neutropenic fever, pruritus, rash, secondary malignancies, urticaria, vision loss Genataxyl >10% Flushing (28%), ECG abnormal (14% to 23%), edema (21%), hypotension (4% to 12%), Alopecia (87%), rash (12%), Nausea/vomiting (52%), diarrhea (38%), mucositis (17% to 35%; grades 3/4: up to 3%), stomatitis (15%; most common at doses >390 mg/m 2 ), abdominal pain (with intraperitoneal paclitaxel) Neutropenia (78% to 98%; grade 4: 14% to 75%; onset 8-10 days, median nadir 11 days, recovery days), leukopenia (90%; grade 4: 17%), anemia (47% to 90%; grades 3/4: 2% to 16%), thrombocytopenia (4% to 20%; grades 3/4: 1% to 7%), bleeding (14%), Alkaline phosphatase increased (22%), AST increased (19%), Injection site reaction (erythema, tenderness, skin discoloration, swelling: 13%), Peripheral neuropathy (42% to 70%; grades 3/4: up to 7%), arthralgia/myalgia (60%), weakness (17%), Creatinine increased (observed in KS patients only: 18% to 34%; severe: 5% to 7%), Hypersensitivity reaction (31% to 45%; grades 3/4: up to 2%),infection (15% to 30%) 1% to 10% Bradycardia (3%), tachycardia (2%), hypertension (1%), rhythm abnormalities (1%), syncope (1%), venous thrombosis (1%), Nail changes (2%), Febrile neutropenia (2%), Bilirubin increased (7%), Dyspnea (2%) <1% Anaphylaxis, ataxia, atrial fibrillation, AV block, back pain, cardiac conduction abnormalities, cellulitis, CHF, chills, conjunctivitis, dehydration, enterocolitis, extravasation recall, hepatic encephalopathy, hepatic necrosis, induration, intestinal obstruction, intestinal perforation, interstitial pneumonia, ischemic colitis, lacrimation increased, 28

29 maculopapular rash, malaise, MI, necrotic changes and ulceration following extravasation, neuroencephalopathy, neutropenic enterocolitis, ototoxicity (tinnitus and hearing loss), pancreatitis, paralytic ileus, phlebitis, pruritus, pulmonary embolism, pulmonary fibrosis, radiation recall, radiation pneumonitis, renal insufficiency, seizure, skin exfoliation, skin fibrosis, skin necrosis, Stevens-Johnson syndrome, supraventricular tachycardia, toxic epidermal necrolysis, ventricular tachycardia (asymptomatic), visual disturbances (scintillating scotomata) Navelbine >10% Alopecia (12% to 30%), Nausea (31% to 44%; grade 3: 1% to 2%), constipation (35%; grade 3: 3%), vomiting (20% to 31%; grade 3: 1% to 2%), diarrhea (12% to 17%), Leukopenia (83% to 92%; grade 4: 6% to 15%), granulocytopenia (90%; grade 4: 36%; nadir: 7-10 days; recovery days; dose-limiting), neutropenia (85%; grade 4: 28%), anemia (83%; grades 3/4: 9%), AST increased (67%; grade 3: 5%; grade 4: 1%), total bilirubin increased (5% to 13%; grade 3: 4%; grade 4: 3%), Injection site reaction (22% to 28%; includes erythema, vein discoloration), injection site pain (16%), Weakness (36%), peripheral neuropathy (25%; grade 3: 1%; grade 4: <1%) Creatinine increased (13%) 1% to 10% Vasculitis Chest pain (5%), Rash (<5%), Gastrointestinal: Paralytic ileus (1%), Hematologic: Neutropenic fever/sepsis (8%; grade 4: 4%), thrombocytopenia (3% to 5%; grades 3/4: 1%), Local: Phlebitis (7% to 10%), Neuromuscular & skeletal: Loss of deep tendon reflexes (<5%), myalgia (<5%), arthralgia (<5%), jaw pain (<5%), Otic: Ototoxicity ( 1%), Respiratory: Dyspnea (7%) <1% Abdominal pain, allergic reactions, anaphylaxis, angioedema, back pain, DVT, dysphagia, esophagitis, flushing, gait instability, headache, hemorrhagic cystitis, hyper-/hypotension, hyponatremia, intestinal necrosis, intestinal obstruction, intestinal perforation, interstitial pulmonary changes, local rash, local urticaria, MI (rare), mucositis, muscle weakness, pancreatitis, paralytic ileus, pneumonia, pruritus, pulmonary edema, pulmonary embolus, radiation recall (dermatitis, esophagitis), skin blistering, syndrome of inappropriate ADH secretion, tachycardia, thromboembolic events, tumor pain, urticaria, vasodilation Oxaliplatin >10% Fatigue (61%), fever (25%), pain (14%), headache (13%), insomnia (11%), Nausea (64%), diarrhea (46%), vomiting (37%), abdominal pain (31%), constipation (31%), anorexia (20%), stomatitis (14%), Anemia (64%; grades 3/4: 1%), thrombocytopenia (30%; grades 3/4: 3%), leukopenia (13%), AST increased (54%; grades 3/4: 4%), ALT increased (36%; grades 3/4: 1%), total bilirubin increased (13%; grades 3/4: 5%), Peripheral neuropathy (may be dose limiting; 76%; acute 65%; grades 3/4: 5%; persistent 43%; grades 3/4: 3%), back pain (11%), Dyspnea (13%), cough (11%) 1% to 10% Edema (10%), chest pain (5%), peripheral edema (5%), flushing (3%), thromboembolism (2%), Dizziness (7%), Rash (5%), alopecia (3%), hand-foot syndrome (1%), Dehydration (5%), hypokalemia (3%), Dyspepsia (7%), taste perversion (5%), flatulence (3%), mucositis (2%), gastroesophageal reflux (1%), dysphagia (acute 1% to 2%), Dysuria (1%), Neutropenia (7%), Injection site reaction (9%; redness/swelling/pain), Rigors (9%), arthralgia (7%), Abnormal lacrimation (1%), Serum creatinine increased (5% to 10%), URI (7%), rhinitis (6%), epistaxis (2%), pharyngitis (2%), 29

30 pharyngolaryngeal dysesthesia (grades 3/4: 1% to 2%), Allergic reactions (3%); hypersensitivity (includes urticaria, pruritus, facial flushing, shortness of breath, bronchospasm, diaphoresis, hypotension, syncope: grades 3/4: 2% to 3%); hiccup (2%) <1% Acute renal failure, alkaline phosphatase increased, anaphylactic/anaphylactoid reactions, anaphylactic shock, angioedema, aphonia, ataxia, colitis, cranial nerve palsies, deep tendon reflex loss, deafness, diplopia, dysarthria, dysphonia, eosinophilic pneumonia, extravasation (including necrosis), fasciculations, gait abnormal, hematuria, hemolysis, hemolytic anemia (immuno-allergic), hemolytic uremia syndrome, hemorrhage, hepatic failure, hepatitis, hepatotoxicity, hypertension, hypomagnesemia, hypoxia, ileus, INR increased, interstitial lung diseases, interstitial nephritis (acute), intestinal obstruction, intracerebral bleeding, Lhermittes' sign, metabolic acidosis, muscle spasm, myoclonus, neutropenic fever, neutropenic sepsis, nodular regenerative hyperplasia, optic neuritis, pancreatitis, peliosis, prothrombin time increased, ptosis, rectal hemorrhage, rhabdomyolysis, seizure, sepsis, thrombocytopenia (immuno-allergic), trigeminal neuralgia, tubular necrosis (acute), veno-occlusive liver disease (sinusoidal obstruction syndrome and perisinusoidal fibrosis), visual disturbance (acuity decreased, field disturbance, transient loss) Campto >10% Vasodilation (9% to 11%), Cholinergic toxicity (47% - includes rhinitis, increased salivation, miosis, lacrimation, diaphoresis, flushing and intestinal hyperperistalsis); fever (44% to 45%), pain (23% to 24%), dizziness (15% to 21%), insomnia (19%), headache (17%), chills (14%), Alopecia (46% to 72%), rash (13% to 14%), Dehydration (15%), Diarrhea, late (83% to 88%; grade 3/4: 5% to 31%), diarrhea, early (43% to 51%; grade 3/4: 6% to 22%), nausea (70% to 86%), abdominal pain (57% to 68%), vomiting (62% to 67%), cramps (57%), anorexia (44% to 55%), constipation (30% to 32%), mucositis (30%), weight loss (30%), flatulence (12%), stomatitis (12%), Anemia (60% to 97%; grades 3/4: 5% to 22%), leukopenia (63% to 96%, grades 3/4: 14% to 28%), thrombocytopenia (96%, grades 3/4: 1% to 4%), neutropenia (30% to 96%; grades 3/4: 14% to 31%), Bilirubin increased (84%), alkaline phosphatase increased (13%), Weakness (69% to 76%), back pain (14%), Dyspnea (22%), cough (17% to 20%), rhinitis (16%), Diaphoresis (16%), infection (14%) 1% to 10% Edema (10%), hypotension (6%), thromboembolic events (5%), Somnolence (9%), confusion (3%), Abdominal fullness (10%), dyspepsia (10%), Neutropenic fever (grades 3/4: 2% to 6%), hemorrhage (grades 3/4: 1% to 5%), neutropenic infection (grades 3/4: 1% to 2%), AST increased (10%), ascites and/or jaundice (grades 3/4: 9%), Pneumonia (4%) <1% postmarketing, and/or case reports: ALT increased, amylase increased, anaphylactoid reaction, anaphylaxis, angina, arterial thrombosis, bleeding, bradycardia, cardiac arrest, cerebral infarct, cerebrovascular accident, circulatory failure, colitis, deep thrombophlebitis, dysrhythmia, embolus, gastrointestinal bleeding, gastrointestinal obstruction, hepatomegaly, hiccups, hyperglycemia, hypersensitivity, hyponatremia, ileus, interstitial lung disease, intestinal perforation, ischemic colitis, lipase increased, lymphocytopenia, megacolon, MI, muscle cramps, myocardial ischemia, pancreatitis, paresthesia, peripheral vascular disorder, pulmonary embolus; pulmonary toxicity (dyspnea, fever, reticulonodular infiltrates on chest x-ray); renal failure (acute), renal impairment, syncope, thrombophlebitis, thrombosis, typhlitis, ulceration, ulcerative colitis, vertigo 30

31 Eposin >10% Alopecia (8% to 66%), Ovarian failure (38%), amenorrhea, Nausea/vomiting (31% to 43%), anorexia (10% to 13%), diarrhea (1% to 13%), mucositis/esophagitis (with high doses), Leukopenia (60% to 91%; grade 4: 3% to 17%; onset: 5-7 days; nadir: 7-14 days; recovery: days), thrombocytopenia (22% to 41%; grades 3/4: 1% to 20%; nadir 9-16 days), anemia (up to 33%) 1% to 10% Hypotension (1% to 2%; due to rapid infusion), Stomatitis (1% to 6%), abdominal pain (up to 2%), Hepatic toxicity (up to 3%), Peripheral neuropathy (1% to 2%), Anaphylactic-like reaction (I.V. infusion: 1% to 2%; including chills, fever, tachycardia, bronchospasm, dyspnea) <1% Anovulatory cycles, back pain; blindness (transient, cortical); CHF, constipation, cough, cyanosis, diaphoresis, dysphagia, erythema; extravasation (induration, necrosis, swelling); facial swelling, fatigue, fever, headache, hepatic toxicity, hepatitis, hyperpigmentation, hypersensitivity, hypersensitivity-associated apnea, hypomenorrhea, interstitial pneumonitis, laryngospasm, maculopapular rash, malaise, metabolic acidosis, MI, optic neuritis, perivasculitis, pruritus, pulmonary fibrosis, radiation-recall dermatitis, rash, seizure, somnolence, Stevens-Johnson syndrome, tachycardia, taste perversion, thrombophlebitis, tongue swelling, toxic epidermal necrolysis, urticaria, weakness Mitomycin >10% CHF (3% to 15%), Fever (14%), Alopecia, nail banding/discoloration, Nausea, vomiting and anorexia (14%), Anemia (19% to 24%); myelosuppression, common, dose limiting, delayed (Onset: 3 weeks; Nadir: 4-6 weeks; Recovery: 6-8 weeks) 1% to 10% Rash, Stomatitis, Paresthesia, Creatinine increase (2%), Interstitial pneumonitis, infiltrates, dyspnea, cough (7%) <1% <1% (Limited to important or life-threatening): Extravasation reactions, hemolytic uremic syndrome, malaise, pruritus, renal failure, bladder fibrosis/contraction (intravesical administration) Erbitux >10% Fatigue (89%), pain (17% to 51%), headache (26% to 33%), insomnia (10% to 30%), fever (27% to 30%), confusion (15%), anxiety (14%), chills/rigors (13%), depression (7% to 13%), Acneiform rash (76% to 90%; grades 3/4: 1% to 17%; onset: 14 days), rash (89%), dry skin (49%), pruritus (11% to 40%), nail changes/disorder (16% to 21%), Hypomagnesemia (55%; grades 3/4: 6% to 17%), Abdominal pain (26% to 59%), constipation (26% to 46%), diarrhea (25% to 39%), vomiting (25% to 37%), nausea (mild-to-moderate 29%), weight loss (7% to 27%), anorexia (23%), stomatitis (10% to 25%), xerostomia (11%), Weakness (45% to 48%), bone pain (15%), Dyspnea (17% to 48%), cough (11% to 29%), Infection (13% to 35%), infusion reaction (15% to 21%; grades 3/4: 2% to 5%; 90% of severe reactions occurred with first infusion) 31