確定病人姓名診斷及化療醫(yī)囑包括藥名清楚劑量給藥方式及時間

1、癌癥病患常見問題的處理,血液暨腫瘤科R5 林煥超,Multidiscipline Treatment of Cancer,Clinical oncologistSurgeonRadiation oncologistPathologistRadiologist,The Description of Cancer Patients,1.The pattern of presenting symptoms and signs.2.

2、The evidence of diagnosis.3.The disease extent.4.The treatment plan.5.The effects and side effects of treatments.6.The ongoing problems.,Pathophysiology of Cancer,Local effects: 1. Tumor necrosis, infection, bleed

3、ing. 2. Tumor invasion of adjacent structure.,Pathophysiology of Cancer,Remote effects: 1. Tumor production: hormones, growth factors, cytokines, other peptides. 2. Tumor-evoked production:

4、 a. Immune cells: antibodies, immune complex. b. Non-immune cells: other peptides.,如何給予化學治療藥物,,,DNA synthesis,,Antimetabolites,,,DNA,DNA transcription,DNA duplication,Mitosis,Alkylating agents,,Spindle poisons,,,,

5、,Intercalating agents,Cellular level,Action sites of cytotoxic agents,,,,,6-MERCAPTOPURINE6-THIOGUANINEMETHOTREXATE5-FLUOROURACILHYDROXYUREACYTARABINE,PURINE SYNTHESIS,PYRIMIDINE SYNTHESIS,RIBONUCLEOTIDES,DEOXYRI

6、BONUCLEOTIDES,DNA,RNA,PROTEINS,MICROTUBULES,ENZYMES,L-ASPARAGINASEVINCA ALKALOIDSTAXOIDS,ALKYLATING AGENTSANTIBIOTICS,,,,,,,,,,,,,,,,,,,,,,,ETOPOSIDE,,,Action sites of cytotoxic agents,,化學治療可以,延長轉移患者的存活期 @ Pr

7、imary chemotherapy 減輕癌癥引起的不適 @ Palliative chemotherapy 增加手術或放射治療的療效 @ Neoadjuvant & adjuvant @ Concommitent radiosensitizer 改善臨床的治療方式,化學藥物的給藥,靜脈注射: 大多數(shù)藥物長期低劑量灌注短期靜脈輸注靜脈推注口服藥物: VP-16, UFT,

8、 Xeloda, Hydroxyurea, 6-MP, 6-TG,化學藥物的給藥,局部化學治療動脈內注射: 肝臟腫瘤 腹腔內注射: 卵巢癌, 腸胃道癌肋膜腔/心包膜腔內注射: 癌性積液 脊髓腔內注射: 腦膜侵犯腦室內注射: 腦膜侵犯 經(jīng)皮給藥: 皮膚癌,化學藥物的靜脈給藥,依藥物,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毒性反應 Adriamycin, Epirubicin不同的注射方式

9、有不同的殺死癌細胞的機制 5-FU,化學藥物給藥前應注意,確定病人姓名, 診斷及化療醫(yī)囑包括藥名清楚, 劑量, 給藥方式及時間Mitoxantrone, Mitomycin-CFluorouracil, FluconazoleVincristine, Vinblastine,化學藥物給藥前,選定適當?shù)淖⑸湮恢貌豢墒褂密浗M織少又有重要構造的部位 手背, 腹股溝等部位不可使用血液流通不佳的部位不可使用關節(jié)部位最佳位置

10、為前臂手掌側Port-A 為最佳輸注管道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, 藥物名稱, 劑量,給藥方式及灌注時間長短. 依醫(yī)囑所述方式給藥, 包括給藥的順序, 若有困難應立即聯(lián)絡醫(yī)師. Ara-C: push, subcutaneous, slow infusion, long term infusion. etc. Cisplatin + Taxol. CDDP + MTX,

11、化學藥物的給藥後,不同的藥物的給藥後注意事項根據(jù)其常見毒性反應可能不同注意嚴重的立即性毒性反應Cisplatin: hydration & urine outputAdriamycin/ Epirubicin: heart failureHigh dose Methotrexate: renal failureCyclophosphamide: hemorrhagic cystitis,MucositisNaus

12、ea/vomitingDiarrheaCystitisSterilityMyalgiaNeuropathy,AlopeciaPulmonary fibrosisCardiotoxicityLocal reactionRenal failureMyelosuppressionPhlebitis,,,,,,,,,,,,,,,Side effects of chemotherapy,INCREASED E

13、FFICACY,Different mechanisms of action Compatible side effects Different mechanisms of resistance,ACTIVITY,SAFETY,Aim of combination therapy,,會引起組織壞死的藥物,Vinka alkaloids: Vincristine(Oncovin), Vinblastine, Vin

14、orelbine(Navelbine)Anthracyclines: Epirubicin, IdarubicinMitomycin-C, BCNU, DTIC Taxoids, TopotecanMithramycin, Nitrogen Mustard VP-16, Cisplatin Fludarabine, Gemcitabine, Irinotecan,化學藥物外滲的處置,及早發(fā)現(xiàn),立即停止輸注局部冷敷Cold

15、 Compression for 30 min. Q6H抬高患處,減少水腫治療可能之局部感染保持壞死皮膚所形成的水泡的完整及消毒開與止痛藥物,甚至morphine若有皮膚表面壞死, 請教整形外科共同評估,甚至需要植皮.,Chemotherapy-associated Emesis,Type of Treatment-related Emesis,1.Acute-phase symptoms: Correlated

16、with serotonin (5-HT) release from enterochromaffin cells. Emetic signals are propagated at local 5-HT3 receptors.,Type of Treatment-related Emesis,2.Delayed-phase symptoms: Not to be relat

17、ed 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:

18、 An aversive conditioned response Develops after repeated antineoplastic treatments that are characterized by poor emetic control. Complete control throughout antineoplastic treatment remains the

19、 best preventive strategy.,Antiemetic Options,1. Serotonin (5-HT3) receptor antagonists: Granisetron (Kytril)Ondansetron (Zofran)More effective and safer to use then other types of antiemetics.,Serotonin An

20、tagonists,Ondansetron, Granisetron.健保給付規(guī)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 Antagonists,3.惡性腫瘤患者使用中性致吐劑cisplatin劑量>30，< 50mg/m2可預防性使用一日劑量且發(fā)生嚴重延遲性嘔

21、吐，使用dexamethasone及metoclopramide無效之病例，每療程使用以不得超過五日為原則。須檢附病歷摘要及使用 dexamethasone及 metoclopramide 無效之記錄。,Serotonin Antagonists,4.接受腹部放射照射之癌癥病人，得依下列規(guī)範使用ondansetron及granisetron： (1)total body or half body irradiation (

22、2)pelvis or upper abdominal region of single irradiation dose> 6 Gy (3)腹部放射治療中產生嘔吐，經(jīng)使用dexamethasone、metoclopramide或prochlorperazine等傳統(tǒng)止吐劑無效，仍發(fā)生嚴重嘔吐之患者。,Antiemetic Options,2. Steroids:Acute-phase symptoms:

23、 effective against mildly to moderately symptoms. Delayed-phase symptoms: most active agents. Dexamethasone (2-20mg) & methylprednisolone + 5-HT3- and D2-receptor antagonists.,Antiemetic Op

24、tions,3.  Metoclopramide: A weak competitive 5-HT3-receptor antagonist at high dosages.4. Benzodiazepines: Lorazepam (Ativan). 5. Dopaminergic (D2)-receptor antagonists: Phenot

25、hiazines—Prochlorperazine. Butyrophenones—Haloperidol.,Neutropenic Fever,Neutropenic Fever,Fever: 1 oral temperature > 38.3oC. 2 oral temperatures > 38oC, an hour apart.Neutropenia: ANC (Band

26、 + Neutrophil) < 500/mm3. ANC 500/mm3 ~ 1,000/mm3, with a predicted decline to < 500/mm3 within 48 hours.,Neutropenic Fever,In the absence of white cells: 1. Signs and symptoms of invasive inf

27、ections may be absent. 2. Infections can invade and spread quickly. 3. Fever may be the only manifestation of a potentially life-threatening infection.,Neutropenic Fever,Bacteremia: 10% to 20% Gram-posit

28、ive bacteremia: 70% Coagulase-negative staphylococcus S. aureus.Gram-negative bacteremia: 30% Escherichia coli, Klebsiella sp., Enterobacter sp., and rarely, Pseudomonas aeruginosa.,Neutropenic F

29、ever,Common sites of local infection: The respiratory tract. Sinuses. Skin, soft tissue. Venous catheter entry/exit sites. Urinary tract. Gastrointestinal tract: oral cavity, anus.,Neutropeni

30、c Fever,Laboratory evaluation: CBC/DC, Platelet. Chemistries (hepatic and renal function). Blood cultures. U/A and U/C. CXR.   Any accessible sites of possible infection.,,IDSA 2002 Guidelin

31、es CID 2002; 730-51,Vancomycin,In initial empirical therapy: 1. Clinically suspected serious catheter- related infections. 2. Known colonization with penicillin- and cephalosporin-resistant pneumo

32、cocci or MRSA. 3. B/C gram-(+) bacteria before final identification and susceptibility testing. 4. Hypotension or other evidence of CV impairment.,G-CSF,Filgrastim, Lenograstim.健保給付規(guī)定

33、 (1)造血幹細胞骨髓移植 (2)血液惡性疾病接受靜注化學治療後 (3)先天性或循環(huán)性中性白血球低下癥者 (當白血球數(shù)量少於1000/mm3，或中性白血 球(ANC)少於500/mm3)。,G-CSF,(4)其他惡性疾病患者在接受化學治療後，曾經(jīng)發(fā)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嚴重感染時使用，惟不得作為

34、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 癌癥不受控制、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(shù)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。,癌癥疼痛Cancer Pain,晚期癌癥患者常見癥狀,Pain

35、 89%Fatigue 69%Weakness 66%Lack of energy 61%Dry mouth 57%Constipation 51%Dyspnea 50%Sleep Dis. 49%,Depression 41%Cough 38%Nausea 36%

36、Edema 28%Taste 28%Hoarseness 24%Anxiety 24%Vomiting 23%,癌癥疼痛可由一些簡單的治療方式在90%的患者得到有效的處置Cancer pain can be managed effectively through relatively simple means in up to 90%

37、 of Patients. Unfortunately, pain associated with cancer is frequently undertreated.,疼痛評估的基本原則,相信病人的疼痛抱怨仔細詢問癌癥及疼痛相關病史評估心理狀態(tài)、可請精神科協(xié)助進行理學、神經(jīng)學檢查開立診斷方式：如 CT，bone scan，MRI開始治療疼痛以便利適當檢驗重新評估治療的反應再設計、討論進一步治療方式,治療的基本原則,1

38、.Dose "by mouth" whenever possible.2. Around the clock (ATC): Basal analgesic administration should not be based on an "as needed" (prn) basis.3.Dose by the WHO three-step l

39、adder.,47,WHO Analgesic Ladder,Co-analgesics,Strong Opioids,MorphineOxycodoneHydromorphoneFentanyl-TTS,Relation127.5100,Duration 8 - 12 8 - 12 8 - 1248 - 72,Strong Opioids,Morphine 10mg IV, IM

40、 = 20mg SC = 30mg PO,,Morphine SR,Fentanyl-TTS,DosageIf pain continues:,2 x 30 mgA. 2 x 60 mgB. 3 x 30 mgnever < 8 hrs,12 hrs12 hrs 8 hrs,,25 mg/hA. 50 mg/hB. 25 mg/hnever < 2 days,Eve

41、ry 3. dayEvery 3. dayEvery 2. day,DosageIf pain continues:,Rapid Calculation of Duragesic for Cancer Pain,Divide morphine equivalent dose (mg/day) PO by 2, round off to closest Duragesic patch in mcg/hr EX

42、AMPLE: Pt is on morphine (PO) 180 mg/day -> 180 /2 = 90, round off to Duragesic 100 mcg/hr,癌病代謝性急癥 (Metabolic Emergencies in Oncology),高血鈣癥:病程之變化,Early signs : fatique,lethargy, constipation, nausea

43、and polyuria.Polyuria and nocturia secondary to renal tubular defect in water conservation. ==> DehydrationStupor and coma are signs of severe hypercalcemia,高血鈣癥的鑑別診斷,Endocrine/metabolic disordersCancerInfectiou

44、s diseaseRenal insufficiencyGranulomatous diseasesDietary/drug relatedMilk_alkali syndrome高血鈣癥最常見原因為癌癥及副甲狀腺功能亢進,高血鈣癥的治療,Saline hydration and diureticsSteroids: inhibit bone resorption and decrease GI tract calcium

45、 absorption.most helpful in myeloma, leukemia and breast cancerCalcitonin: increase renal excretion and reduce bone resorption,高血鈣癥的治療(II),Diphosphonates : reduce calcium flux from bone. osteoclast inhibitor.Gall

46、ium nitrate : inhibit bone resorptionMithramycin : kill osteoclasts.,腫瘤融解癥候群,Tumor Lysis Syndrome,腫瘤細胞內含物及其代謝產物大量釋出於血液中所引發(fā)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:

47、 acute urate nephropahy --> obstruction and renal failureHyperkalemia: cardiac arrhythmiasHyperphosphatemia : acute renal failure Hypocalcemia: muscle cramp, cardiac arrhythmias and tetany,Tumor Lysis常見於下列腫瘤,Large

48、tumor burdens, rapid proliferative fraction and sensitive to chemotherapy.High grade lymphoma ,such as Burkit's lymphoma.Leukemia with high leucocyte counts, CML in blastic crisisRarely seen in solid tumors: small

49、cell lung ca, breast cancerFew hours to few days after initiation of treatment,Tumor Lysis臨床癥狀,Oliguria-azotemiaHyperkalemia, hyperphosphatemia, hyperuricemiaTetanyCardiac arrhythmiaHypotension-shockCardiac arrest,

50、如何早期發(fā)現(xiàn) Tumor Lysis,密切檢測Chemistry screen : K+, Ca++, uric acid, PO4,LDH,BUN,creatinine,Tumor Lysis的治療方式,Prevention for high risk patientsHydration 2500-3000ml/sqm/daySodium bicarbonate for alkalinization to urine PH

51、>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

52、 for 1 weekonce tumor lysis developed, monitor the lytes every few hours.Hypocalcemia : calcium gluconateHyperkalemia : Kayexalate (15 gm q6h), 20% dextrose with 10-20 U of insulin /liter.Hyperphosphatemia : aluminu

53、m gel 30cc q3-4 hrs,Tumor Lysis的治療方式,早期使用血液透析potassium >6 mEq/luric acid > 10mg/dlphospharus > 10 mg/dl, symptomatic hypocalcemia and fluid overload.,脊索壓迫癥候群Spinal Cord Compression,脊索Spinal cord壓迫癥候群,硬腦膜外ex

54、tradural的脊索壓迫癥候是惡性腫瘤常見的神經(jīng)學併發(fā)癥.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(jīng)系統(tǒng)傷害.,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,任何可轉移的腫瘤皆可發(fā)生肺癌約佔了15%乳癌, 攝護腺癌, 淋巴瘤, 骨髓瘤及原發(fā)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

55、經(jīng)分布部位的疼痛,腸道及膀胱自主神經(jīng)控制的異常(autonomic dysfunction),肢體無力及被壓迫脊髓相對神經(jīng)節(jié)以下部位的感覺喪失. 疼痛可以是局部的也可以是神經(jīng)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?？梢娪屑棺倒堑钠茐?傳統(tǒng)上是用脊髓腔攝影(myelography)來確定病灶的範圍,阻斷的部位

56、及嚴重程度及是否有其他部位尚未有癥狀的脊髓壓迫. 核磁共振攝影成為這類病患最佳的檢查方式,臨床癥狀,90%以上的患者會有脊椎中線或脊柱旁區(qū)域 的疼痛. 通常再躺下時會加劇, 而在站著或坐著時會減輕神經(jīng)根的壓迫性疼痛(Radicular pain)是一常見的早期癥狀, 疼痛與脊椎間盤疾病, 肋膜發(fā)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,脊椎部位的壓痛.

57、 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(xiàn) 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X光檢查,癌癥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(colla

58、pse),臨床處置及治療,懷疑有這類併發(fā)癥的患者需立即住院並會診神經(jīng)外科醫(yī)師及放射腫瘤?？漆t(yī)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(jīng)外科手術減壓來治療.,Highlight of Leukemia Management,Bleeding diasthesisRisks of life-threatening hemorrhage -- ICH,

59、 DIC, pulmonary hemorrhageFever, neutropenic feverHyperleucocytosisSevere anemiaOrganomegaly,Cytochemical staining,Myeloperoxidase (MPO): AML M1,2,3,4,5Chloroacetate esterase (CAE): M1,2,3,4Alpha-naphthyl butyrate

60、(ANBE): M4,M5PAS: ALL, AML (15%)Tdt: ALLLAP score: leukocyte ALK P stain (80-100)LAP < 20 in CML, PNH,Approach of Acute Leukemia,Blasts≧30%,Peroxidase stain,Positive,Negative,CAE,PAS,Positive,Negative,POS,Neg,AML

61、M1-M4CD13,14,33,65,ANBE,ALLAML M6,7CD41,61Glycophyrin,AML MoCD13,33,65ALLCD2,7,10,19,,,,,,,,,,,,,,M4,M5,CHROMOSOME ANALYSIS,For diagnosist(9,22): CMLt(2,5): Ki-1 lymphoma ALCLt(4,11): biphenotypic leukem

62、iaFor prognosisFavorable: t(8,21), t(15,17), inv(16)Unfavorable: -5/del, -7/del, +8For detection of minimal residual disease,AML-Treatment,Remission induction: Ara-c 100mg/m2/d X7, Idarubicin 12mg / m2/d X3C

63、onsolidation: Standard Ara-c 100mg/m2 X 5, Ida X2High dose Ara-c 1-3gm/m2 Bid X 4daysMaintenance: not helpfulStem cell transplant— Allo-BMT, Allo-PBSCT— ABMT, autologous PBSCT— MUD, no better than HiDAC— All

64、o-minitransplant (mixed chimerism)Acute GVHD, VOD, interstitial pneumonia, TRM 30%,COMMON CHEMOTHERAPY REGIMEN,AMLA) 7 + 3Ara - C 100mg/m2 + N/S or D5W500ml CIV qd or bidIdarubicin 10-12mg/m2×d + N/S 100mlIV

65、 infusion for 1hr (Mitoxantrone same as Idarubicin)B) HDACAra-C 1gm-3gm/m2×bid + N/S 500mlIV infusion for 3-4 hours,Acute Promyelocytic Leukemia ( M3 ),Remission induction : ATRA 45/m2/d WBC > 3000/c

66、umm : ATRA + Idarubicin 12 mg/m2 WBC > 10000/cumm : ATRA + Ida × 3 + Ara – CConsolidation : 7+3 then HIDAC + DNR or IDAMaintenance : 1 yr ATRA or observation ( APL 93 trial ) 5 yr DFS = 70 %

67、Retinoid acid syndrome : weight gain ,hyperleucocytosis ,interstitial pulmonary infiltrate , pleural or pericardial effusion , hypoxemia , hypotension Treatment : dexamethasone 10 mg bid × 3 day,Treatment

68、 of ALL,Remission induction : - standard risk : vincristin , prednisolone - high risk : vincristin , PDN , doxorubicinEarly intensification : L – asparaginase, MTXCNS prophylaxis : MTX , dexamethasoneConsolidat

69、ion : Ara – C , cyclophosphamideMaintenance : 6 MP/MTX , VCR/PDN , VP-16ALLO-BMT, PBSCT ( auto, MUD ),Clinical Practice in Ward,1st WK: FAB subtype (confirm DX), Karyotype, set IV line, cyto-reduction , initiate C/T,

70、blood component, control infection, risk factors2nd WK: C/T, infection, hemorrhage3rd WK: d15 BM exam, folic acid, G-CSF fungal infection, HSV, diarrhea4th WK: recovery of CBC, fever should subside otherwise consid