1、癌癌症病患常見問題症病患常見問題的處理的處理血液暨腫瘤科R5 林煥超Multidiscipline Treatment of Cancer Clinical oncologist Surgeon Radiation oncologist Pathologist RadiologistThe Description of Cancer Patients 1.The pattern of presenting symptoms and signs.2.The evidence of diagnosis.3.The disease extent.4.The treatment plan.5.The
2、effects and side effects of treatments.6.The ongoing problems.Pathophysiology of Cancer Local effects:1.Tumor necrosis,infection,bleeding.2.Tumor invasion of adjacent structure.Pathophysiology of Cancer Remote effects:1.Tumor production:hormones,growth factors,cytokines,other peptides.2.Tumor-evoked
3、 production:a.Immune cells:antibodies,immune complex.b.Non-immune cells:other peptides.如何給予化學治療藥物如何給予化學治療藥物DNA synthesisDNADNA transcriptionDNA duplicationMitosisAction sites of cytotoxic agents6-MERCAPTOPURINE6-THIOGUANINEMETHOTREXATE5-FLUOROURACILHYDROXYUREACYTARABINEL-ASPARAGINASEVINCA ALKALOIDST
4、AXOIDSALKYLATING AGENTSANTIBIOTICSETOPOSIDEAction sites of cytotoxic agents化學治療可以n 延長轉移患者的存活期延長轉移患者的存活期 Primary chemotherapyn 減輕癌症引起的不適減輕癌症引起的不適 Palliative chemotherapyn 增加手術或放射治療的療效增加手術或放射治療的療效 Neoadjuvant&adjuvant Concommitent radiosensitizern 改善臨床的治療方式改善臨床的治療方式化學藥物的給藥靜脈注射靜脈注射:大多數藥物大多數藥物長期低劑量灌注長期低
5、劑量灌注短期靜脈輸注短期靜脈輸注靜脈推注靜脈推注 口服藥物口服藥物:VP-16,UFT,Xeloda,Hydroxyurea,6-MP,6-TG化學藥物的給藥 局部化學治療局部化學治療動脈內注射動脈內注射:肝臟腫瘤肝臟腫瘤 腹腔內注射腹腔內注射:卵巢癌卵巢癌,腸胃道癌腸胃道癌肋膜腔肋膜腔/心包膜腔內注射心包膜腔內注射:癌性積液癌性積液 脊髓腔內注射脊髓腔內注射:腦膜侵犯腦膜侵犯腦室內注射腦室內注射:腦膜侵犯腦膜侵犯 經皮給藥經皮給藥:皮膚癌皮膚癌 化學藥物的靜脈給藥依藥物依藥物,腫瘤的種類而有不同腫瘤的種類而有不同不同的注射方式有不同的治療結果不同的注射方式有不同的治療結果 不同的注射方式有不
6、同的毒性反應不同的注射方式有不同的毒性反應 Adriamycin,Epirubicin 不同的注射方式有不同的殺死癌細胞的不同的注射方式有不同的殺死癌細胞的機制機制 5-FU化學藥物給藥前應注意確定病人姓名確定病人姓名,診斷及化療醫囑診斷及化療醫囑包括藥名清楚包括藥名清楚,劑量劑量,給藥方式及時給藥方式及時間間 Mitoxantrone,Mitomycin-C Fluorouracil,Fluconazole Vincristine,Vinblastine化學藥物給藥前選定適當的注射位置選定適當的注射位置不可使用軟組織少又有重要構造的部位不可使用軟組織少又有重要構造的部位 手背手背,腹股溝等部
7、位腹股溝等部位不可使用血液流通不佳的部位不可使用血液流通不佳的部位不可使用關節部位不可使用關節部位 最佳位置為前臂手掌側最佳位置為前臂手掌側 Port-A 為最佳輸注管道為最佳輸注管道 給藥前要確定靜脈管道通暢給藥前要確定靜脈管道通暢化學藥物的給藥給藥前再確定患者姓名給藥前再確定患者姓名,藥物名稱藥物名稱,劑劑量量,給藥方式及灌注時間長短給藥方式及灌注時間長短.依醫囑所述方式給藥依醫囑所述方式給藥,包括給藥的順序包括給藥的順序,若有困難應立即聯絡醫師若有困難應立即聯絡醫師.Ara-C:push,subcutaneous,slow infusion,long term infusion.etc.
8、Cisplatin+Taxol.CDDP+MTX化學藥物的給藥後 不同的藥物的給藥後注意事項根據其常不同的藥物的給藥後注意事項根據其常見毒性反應可能不同見毒性反應可能不同 注意嚴重的立即性毒性反應注意嚴重的立即性毒性反應Cisplatin:hydration&urine outputAdriamycin/Epirubicin:heart failureHigh dose Methotrexate:renal failureCyclophosphamide:hemorrhagic cystitisMucositisNausea/vomitingDiarrheaCystitisSterilityM
9、yalgiaNeuropathyAlopeciaPulmonary fibrosisCardiotoxicityLocal reactionRenal failureMyelosuppressionPhlebitisSide effects of chemotherapy Different mechanisms of action Compatible side effects Different mechanisms of resistanceAim of combination therapy會引起組織壞死的藥物會引起組織壞死的藥物 Vinka alkaloids:Vincristine
10、(Oncovin),Vinblastine,Vinorelbine(Navelbine)Anthracyclines:Epirubicin,Idarubicin Mitomycin-C,BCNU,DTIC Taxoids,Topotecan Mithramycin,Nitrogen Mustard VP-16,Cisplatin Fludarabine,Gemcitabine,Irinotecan 化學藥物外滲的處置及早發現及早發現,立即停止輸注立即停止輸注局部冷敷局部冷敷 Cold Compression for 30 min.Q6H抬高患處抬高患處,減少水腫減少水腫治療可能之局部感染治療可
11、能之局部感染保持壞死皮膚所形成的水泡的完整及消毒保持壞死皮膚所形成的水泡的完整及消毒開與止痛藥物開與止痛藥物,甚至甚至morphine若有皮膚表面壞死若有皮膚表面壞死,請教整形外科共同評估請教整形外科共同評估,甚至需要植皮甚至需要植皮.Chemotherapy-associated EmesisType of Treatment-related Emesis 1.Acute-phase symptoms:Correlated with serotonin(5-HT)release from enterochromaffin cells.Emetic signals are propagated
12、 at local 5-HT3 receptors.Type of Treatment-related Emesis 2.Delayed-phase symptoms:Not to be related to serotonin.Severity and duration often correlate with drug dosage.Nausea severity reportedly is similar during both phases.Type of Treatment-related Emesis 3.Anticipatory emetic symptoms:An aversi
13、ve conditioned response Develops after repeated antineoplastic treatments that are characterized by poor emetic control.Complete control throughout antineoplastic treatment remains the best preventive strategy.Antiemetic Options1.Serotonin(5-HT3)receptorantagonists:Granisetron(Kytril)Ondansetron(Zof
14、ran)More effective and safer to use then other types of antiemetics.Serotonin AntagonistsOndansetron,Granisetron.健保給付規定健保給付規定1.骨髓移植患者接受高劑量化學治療時。2.惡性腫瘤患者使用cisplatin劑量超過50mg/m2可預防性使用一日劑量。Delay vomiting每療程使用以不得超過五日為原則Serotonin Antagonists3.惡性腫瘤患者使用中性致吐劑cisplatin劑量30，6 Gy (3)腹部放射治療中產生嘔吐，經使用dexamethasone
15、、metoclopramide或prochlorperazine等傳統止吐劑無效，仍發生嚴重嘔吐之患者。Antiemetic Options2.Steroids:Acute-phase symptoms:effective against mildly to moderately symptoms.Delayed-phase symptoms:most active agents.Dexamethasone(2-20mg)&methylprednisolone +5-HT3-and D2-receptor antagonists.Antiemetic Options3.Metocloprami
16、de:A weak competitive 5-HT3-receptor antagonist at high dosages.4.Benzodiazepines:Lorazepam(Ativan).5.Dopaminergic(D2)-receptorantagonists:PhenothiazinesProchlorperazine.ButyrophenonesHaloperidol.Neutropenic FeverNeutropenic Fever Fever:1 oral temperature 38.3oC.2 oral temperatures 38oC,an hour apar
17、t.Neutropenia:ANC(Band+Neutrophil)500/mm3.ANC 500/mm3 1,000/mm3,with a predicted decline to 500/mm3 within 48 hours.Neutropenic FeverIn the absence of white cells:1.Signs and symptoms of invasive infections may be absent.2.Infections can invade and spread quickly.3.Fever may be the only manifestatio
18、n of a potentially life-threatening infection.Neutropenic Fever Bacteremia:10%to 20%Gram-positive bacteremia:70%Coagulase-negative staphylococcus S.aureus.Gram-negative bacteremia:30%Escherichia coli,Klebsiella sp.,Enterobacter sp.,and rarely,Pseudomonas aeruginosa.Neutropenic Fever Common sites of
19、local infection:The respiratory tract.Sinuses.Skin,soft tissue.Venous catheter entry/exit sites.Urinary tract.Gastrointestinal tract:oral cavity,anus.Neutropenic Fever Laboratory evaluation:CBC/DC,Platelet.Chemistries(hepatic and renal function).Blood cultures.U/A and U/C.CXR.Any accessible sites of
20、 possible infection.IDSA 2002 Guidelines CID 2002;730-51Vancomycin In initial empirical therapy:1.Clinically suspected serious catheter-related infections.2.Known colonization with penicillin-and cephalosporin-resistant pneumococci or MRSA.3.B/C gram-(+)bacteria before final identification and susce
21、ptibility testing.4.Hypotension or other evidence of CV impairment.G-CSF Filgrastim,Lenograstim.健保給付規定 (1)造血幹細胞骨髓移植 (2)血液惡性疾病血液惡性疾病接受靜注化學治療後 (3)先天性或循環性中性白血球低下症者 (當白血球數量少於1000/mm3，或中性白血 球(ANC)少於500/mm3)。G-CSF (4)其他惡性疾病患者其他惡性疾病患者在接受化學治療後，曾經發生白血球少於1000/mm3，或中性白血球(ANC)少於500/mm3者，在下一療程即可使用。(5)重度再生不良性貧血病人
22、嚴重感染時使用，惟不得作為此類病人之預防性使用。(6)化學治療，併中性白血球小於100/mm3 癌症不受控制、肺炎、低血壓、多器官衰竭或侵犯性微菌感染等危機程度高之感染。使用本品之患者應檢附治療記錄，其內容需包括診斷、白血球數量變化、所使用之化學治療藥物名稱、劑量及使用本品劑量，如白血球超過4000/mm3時或中性白血球超過2000/mm3時，應即停藥。癌癌症症疼痛疼痛Cancer Pain 晚期癌症患者常見症狀 Pain 89%Fatigue 69%Weakness 66%Lack of energy 61%Dry mouth 57%Constipation 51%Dyspnea 50%Sl
23、eep Dis.49%Depression 41%Cough 38%Nausea 36%Edema 28%Taste 28%Hoarseness 24%Anxiety 24%Vomiting 23%癌癌症症疼痛可由一些簡單的治療方疼痛可由一些簡單的治療方式在式在90%90%的患者得到有效的處置的患者得到有效的處置Cancer pain can be managed effectively through relatively simple means in up to 90%of Patients.Unfortunately,pain associated with cancer is fre
24、quently undertreated.疼痛評估的基本原則評估的基本原則1.相信病人的疼痛抱怨2.仔細詢問癌症及疼痛相關病史3.評估心理狀態、可請精神科協助4.進行理學、神經學檢查5.開立診斷方式：如 CT，bone scan，MRI6.開始治療疼痛以便利適當檢驗7.重新評估治療的反應8.再設計、討論進一步治療方式治療的基本原則治療的基本原則 1.Dose by mouth whenever possible.2.Around the clock(ATC):Basal analgesic administration should not be based on an as needed (
25、prn)basis.3.Dose by the WHO three-step ladder.47WHO Analgesic LadderStrong Opioids Non-OpioidsMorphine,Oxycodone,Hydromorphone,TTS-Fentanyl,Methadon,Step 3Weak Opioids Non-OpioidsCodein,Dihydrocodein,Tramadol,Tilidin/NaloxonStep 2Non-OpioidsIbuprofen,Diclofenac,Cox 2“Paracetamol,Metamizol,FlupirtinS
26、tep 1Strong OpioidsMorphineOxycodoneHydromorphoneFentanyl-TTSRelation127.5100Duration 8-12 8-12 8-1248-72Strong Opioids Morphine 10mg IV,IM =20mg SC =30mg POMorphine SRFentanyl-TTSDosageIf pain continues:2 x 30 mgA.2 x 60 mgB.3 x 30 mgnever 8 hrs12 hrs12 hrs 8 hrs 25 mg/hA.50 mg/hB.25 mg/hnever 180/
27、2=90,round off to Duragesic 100 mcg/hr癌病代謝性急症(Metabolic Emergencies in Oncology)高血鈣症:病程之變化 Early signs:fatique,lethargy,constipation,nausea and polyuria.Polyuria and nocturia secondary to renal tubular defect in water conservation.=Dehydration Stupor and coma are signs of severe hypercalcemia高血鈣症的鑑別
28、診斷 Endocrine/metabolic disorders Cancer Infectious disease Renal insufficiency Granulomatous diseases Dietary/drug related Milk_alkali syndrome高血鈣症最常見原因為癌症及副甲狀腺功能亢進高血鈣症最常見原因為癌症及副甲狀腺功能亢進高血鈣症的治療 Saline hydration and diuretics Steroids:inhibit bone resorption and decrease GI tract calcium absorption.mo
29、st helpful in myeloma,leukemia and breast cancer Calcitonin:increase renal excretion and reduce bone resorption 高血鈣症的治療(II)Diphosphonates:reduce calcium flux from bone.osteoclast inhibitor.Gallium nitrate:inhibit bone resorption Mithramycin:kill osteoclasts.腫瘤融解症候群腫瘤融解症候群Tumor Lysis Syndrome腫瘤細胞內含物及
30、其代謝產物大量釋出於血液中所引發的全身性反應Rapid release of intracellular contents into the blood stream 主要代謝異常及其引致之病變 Hyperuricemia:acute urate nephropahy-obstruction and renal failure Hyperkalemia:cardiac arrhythmias Hyperphosphatemia:acute renal failure Hypocalcemia:muscle cramp,cardiac arrhythmias and tetanyTumor Ly
31、sis常見於下列腫瘤 Large tumor burdens,rapid proliferative fraction and sensitive to chemotherapy.High grade lymphoma,such as Burkits lymphoma.Leukemia with high leucocyte counts,CML in blastic crisis Rarely seen in solid tumors:small cell lung ca,breast cancer Few hours to few days after initiation of trea
32、tmentTumor Lysis臨床症狀 Oliguria-azotemia Hyperkalemia,hyperphosphatemia,hyperuricemia Tetany Cardiac arrhythmia Hypotension-shock Cardiac arrest如何早期發現 Tumor Lysis 密切檢測密切檢測 Chemistry screen:K+,Ca+,uric acid,PO4,LDH,BUN,creatinineTumor Lysis的治療方式 Prevention for high risk patients Hydration 2500-3000ml/s
33、qm/day Sodium bicarbonate for alkalinization to urine PH 7 (50-100meq/L)Allopurinol 10 mg/kg/day ,300mg/day(12 hrs before C/T),reduces to 100mg/day if creatinine 2mg%Tumor Lysis的治療方式 Monitor elctrolytes,uric acid,phosphorus,calcium and creatinine daily for 1 week once tumor lysis developed,monitor t
34、he lytes every few hours.Hypocalcemia:calcium gluconate Hyperkalemia:Kayexalate (15 gm q6h),20%dextrose with 10-20 U of insulin/liter.Hyperphosphatemia:aluminum gel 30cc q3-4 hrs Tumor Lysis的治療方式早期使用血液透析早期使用血液透析 potassium 6 mEq/l uric acid 10mg/dl phospharus 10 mg/dl,symptomatic hypocalcemia and flu
35、id overload.脊索壓迫症候群脊索壓迫症候群Spinal Cord Compression脊索Spinal cord壓迫症候群硬腦膜外extradural的脊索壓迫症候是惡性腫瘤常見的神經學併發症.不論是硬腦膜外的腫瘤或是較罕見的由脊髓內腫瘤所引起者,如未有立即的診斷及迅速的治療,皆可引起永久性的神經系皆可引起永久性的神經系統傷害統傷害.部位分布部位分布 硬腦膜外轉移 頸椎 10%胸椎 70%腰椎及薦椎 20%可能的腫瘤可能的腫瘤 任何可轉移的腫瘤皆可發生 肺癌約佔了15%乳癌,攝護腺癌,淋巴瘤,骨髓瘤及原發布為不明的轉移癌則各約佔 了10%.臨床徵候被壓迫脊髓相對神經分布部位的疼痛,
36、腸道及膀胱自主神經控制的異常(autonomic dysfunction),肢體無力及被壓迫脊髓相對神經節以下部位的感覺喪失.疼痛可以是局部的也可以是神經根壓迫式(radicular pain).受侵犯部位的脊椎可有壓痛(point tenderness).放射線及實驗室的診斷要做可能侵犯部位的脊椎X光檢查,也常可見有脊椎骨的破壞.傳統上是用脊髓腔攝影(myelography)來確定病灶的範圍,阻斷的部位及嚴重程度及是否有其他部位尚未有症狀的脊髓壓迫.核磁共振攝影核磁共振攝影成為這類病患最佳的檢查方式臨床症狀臨床症狀 90%以上的患者會有脊椎中線或脊柱旁區域 的疼痛.通常再躺下時會加劇,而在站
37、著或坐著時會減輕 神經根的壓迫性疼痛(Radicular pain)是一常見的早期症狀,疼痛與脊椎間盤疾病,肋膜發炎,膽囊炎及胰臟炎的疼痛類似.下肢的無力及麻木感但無感覺異常(paresthesias)便秘或是大解失禁理學檢查理學檢查 脊椎部位的壓痛.若加上脊髓病變的徵候則極有可能有硬腦膜上的轉移腫瘤.被壓迫的脊椎部位以下可出現 DTR增加(hyperactive)Babinski 徵候陽性 運動無力 感覺異常(hypesthesia)肛門括約肌張力減低脊椎脊椎X光檢查光檢查 癌症患者有背痛者皆應做脊椎X光檢查 脊椎X光檢查在80%的患者可判斷有無硬腦膜外的轉移.最常見的有 pedicles的喪失,脊椎體的破壞及脊椎體的崩解(collapse)臨床處置及治療懷疑有這類併發症的患者需立即住院並會診神經外科醫師及放射腫瘤專科醫師.需要立即且積極的使用類固醇(例如dexamethasone,4-10 mg IV q6h)緊急的放射治療或是神經外科手術減壓來治療.Blasts30%Peroxidase stainPositiveNegativeCAEPASPositiveNegativePOSNegAMLM1-M4CD13,14,33,65ANBEALLAML M6,7CD41,61GlycophyrinAML MoCD13,33,65ALLCD2,7,10,19M4,M5
