HD

HD and HD p1 INDICATION Recurrent or metastatic breast cancer 1 DOSAGE AND SCHEDULING CHEMOTHERAPY REGIMEN 1 (Cycled every 21 days until disease progression or unacceptable toxicity ) Loading: 8 mg/kg IVF over 1.5hrs Maintenance: 6 mg/kg IVF over 1.5hrs * 60 mg/m 2 IVF over 1hr * Modified from reference 1 (Marty M, et al. 2005): 100 mg/m 2 OR (Cycled every 21 days until disease progression or unacceptable toxicity ) * Loading: 4 mg/kg IVF over 1.5hrs Maintenance: 2 mg/kg IVF over 1.5hrs 60 mg/m 2 IVF over 1hr * Modified from reference 1 (Marty M, et al. 2005): 100 mg/m 2 DAY 1 2 3 4 5 6 7 8 21 DAY 1 2 3 4 5 6 7 8 15 21 SUPPORTIVE MEDICATIONS Prophylaxis of acute and delayed emesis 2,3 Acute emesis Delayed emesis Emetogenicity Antiemetics Day 1 Day 2 Day 3 Day 4 Day 5 Corticosteroid, OR Low risk Dopaminergic blockers Pre-medication to prevent acute emesis Corticosteroid No additional dexamethasone needed on day 1 if dexamethasone already given for fluid retention, OR Dexamethasone 8 mg PO/IV Day 1 OR Dopaminergic blockers Metoclopramide 10-40 mg PO/IV before dose and then as needed q4-6 hrs Day 1 Other supportive therapy 6 Patients experienced mild or moderate infusion-related reactions with the first dose, could be treated with acetaminophen and diphenhydramine. Premedication for fluid retention and hypersensitivity: Corticosteroid Dexamethasone 8 mg PO BID for 3 days, starting 1 day prior to docetaxel

DOSAGE MODIFICATIONS 4,5 HD p2 Drug Renal impairment Hepatic impairment --- -- --- Bilirubin >ULN or AST and/or ALT >1.5 x ULN concomitant with ALP> 2.5 x ULN: Avoid use Adjustment for toxicities 4,5 : Cardiotoxicity: LVEF (left ventricular ejection fraction) 16% decrease from baseline or LVEF below normal limits and 10% decrease from baseline: Withhold treatment for at least 4 weeks and repeat LVEF every 4 weeks. May resume trastuzumab treatment if LVEF returns to normal limits within 4-8 weeks and remains at 15% decrease from baseline value. Discontinue permanently for persistent (>8 weeks) LVEF decline or for >3 incidents of treatment interruptions for cardiomyopathy. Infusion-related events: 1. Mild-moderate infusion reactions: Decrease infusion rate. 2. Dyspnea, clinically significant hypotension: Interrupt infusion. 3. Severe or life-threatening infusion reactions: Discontinue. Patients should receive a reduced dose (60 mg/m 2 ) of docetaxel when: 1. persistent febrile neutropenia (while on G-CSF) 2. severe/cumulative cutaneous reactions 3. moderate neurosensory effects (signs/symptoms) 4. grade 3 or 4 stomatitis Discontinue therapy with persistent toxicities after dosage reduction PREPARATION 4,5 Stable in NS; incompatible with D5W. Reconstituted with a vial of solvent (13% ethanol in water for injection). Diluted with 100-250 ml NS or D5W to a final concentration of 0.3 to 0.74 mg/ml ADMINISTRATION 4.5 Administer by IV infusion; loading doses are infused over 90 minutes; maintenance doses may be infused over 30 minutes if tolerated. Do not administer with D5W. Do not administer I.V. push or by rapid bolus. Infusion over 60 minutes. Infusion should be completed within 4 hours of final preparation. MONITORING PARAMETERS 4,5,6 Cardiac and left ventricular ejection fraction assessments, such as ECG, ECHO and/or MUGA(multiple gated acquisition) scan; baseline, every 3 months during and upon completion of treatment, and then every 6 months for at least 2 years. Complete blood cell counts with differential, liver function tests, serum electrolytes, and serum creatinine periodically during therapy (eg, every week). Neutropenia is dose-limiting. Vital signs should be monitored during infusion. Patients should be routinely examined for the occurrence of fluid retention or cutaneous reactions. Periodic neurologic examination is advised to detect sensory neuropathy.

HD p3 Cardiac function by echocardiography should be assessed in patients to be treated with docetaxel. The serum concentration of the cardiac neurohormone, brain natriuretic peptide (BNP), may be a useful marker in determining docetaxel-induced cardiotoxicity. CONTRAINDICATIONS 4,5 Severe hypersensitivity to docetaxel or any other drugs formulated with polysorbate 80 Severe hepatic impairment ( ALP>2.5 x ULN ) Neutrophil count <1500/mm 3 ADVERSE REACTIONS 1,4,5,6 Regimen 1 Cardiovascular: peripheral edema (40%; grade 3/4: 1%), decrease in LVEF (decrease <15%:63%, decrease 15%:17%, <40%: 1%) Central nervous system: fatigue (24%; grade 3/4: 3%), headache (21%; grade 3/4: 1%) Dermatologic: alopecia (67%; grade 3/4: 10%) Gastrointestinal: nausea (45%),diarrhea (43%; grade 3/4: 5%), vomiting (29%; grade 3/4: 3%), constipation (27%; grade 3/4: 2%), anorexia (22%; grade 3/4: 2%) Hematologic: anemia (grade 3/4: 1%), leucopenia (grade 3/4: 20%), neutropenia (grade 3/4: 32%), febrile neutropenia/neutropenic sepsis (grade 3/4: 23%), Neuromuscular & skeletal: asthenia (45%; grade 3/4: 10%), paraesthesia (32%), myalgia (27%; grade 3/4: 3%), arthralgia (27%; grade 3/4: 4%) Other: pyrexia (30%; grade 3/4: 1%), rash (24%; grade 3/4: 1%) Cardiovascular: severe CHF (congestive heart failure, 0.54%), symptomatic CHF (1.73%), decrease in LVEF(7.08%) Hematologic: febrile neutropenia (23%), neutropenia, grade 3 and 4 (32% to 34%), thrombosis (2.1% to 3.7% ) Hepatic: hepatotoxicity Immunologic: hypersensitivity reaction Renal: nephrotic syndrome Respiratory: interstitial pneumonia (0.2% ), pneumonitis (0.7% ), pulmonary toxicity ((adjuvant), 14% ), respiratory failure Other:infusion reaction (21% to 40% ) Cardiovascular: fluid retention (13% to 60%; dose dependent) Central nervous system: neurosensory events (20% to 58%; including neuropathy), fever (31% to 35%), neuromotor events (16%) Dermatologic: alopecia (56% to 76%), cutaneous events (20% to 48%), nail disorder (11% to 41%) Gastrointestinal: stomatitis (19% to 53%; severe 1% to 8%), diarrhea (23% to 43%; severe: 5% to 6%), nausea (34% to 42%), vomiting (22% to 23%) Hematologic: neutropenia (84% to 99%; grade 4: 75% to 86%; nadir (median): 7 days, duration (severe neutropenia): 7 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) Hepatic: transaminases increased (4% to 19%) Neuromuscular & skeletal: weakness (53% to 66%; severe 13% to 18%), myalgia (3% to 23%) Respiratory: pulmonary events (41%) Miscellaneous: infection (1% to 34%; dose dependent), hypersensitivity (1% to 21%; with premedication 15%)

NHI REIMBURSEMENT INFORMATION HD p4 9.18. ( 如 Herceptin):(91/4/1 93/8/1 95/2/1 99/1/1 99/8/1 99/10/1 101/1/1) 1. 早期乳癌 (99/1/1 99/8/1 99/10/1 101/1/1) (1) 外科手術前後 化學療法 ( 術前輔助治療或輔助治療 ) 治療後, 具 HER2 過度表現 (IHC 3+ 或 FISH+), 且具腋下淋巴結轉移但無遠處臟器轉移之早期乳癌患者, 作為輔助性治療用藥 (99/10/1 101/1/1) (2) 使用至多以一年為限 (99/8/1) 2. 轉移性乳癌 (1) 單獨使用於治療腫瘤細胞上有 HER2 過度表現 (IHC 3+ 或 FISH+), 曾接受過一次以上化學治療之轉移性乳癌病人 (91/4/1 99/1/1) (2) 與 paclitaxel 或 docetaxel 併用, 使用於未曾接受過化學治療之轉移性乳癌病患, 且為 HER2 過度表現 (IHC 3+ 或 FISH+) 者 (93/8/1 95/2/1 99/1/1) (3) 轉移性乳癌且 HER2 過度表現之病人, 僅限先前未使用過本藥品者方可使用 (99/1/1) 3. 經事前審查核准後使用 9.3. :(87/7/1 92/11/1 93/8/1 95/8/1 96/1/1 99/6/1 100/1/1 101/9/1) 1. 乳癌 : (1) 局部晚期或轉移性乳癌 (2) 與 anthracycline 合併使用於腋下淋巴結轉移之早期乳癌之術後輔助性化學治療 (99/6/1) (3) 早期乳癌手術後, 經診斷為三陰性反應且無淋巴轉移的病人, 得作為與 cyclophosphamide 併用 doxorubicin 的化學輔助療法 (101/9/1) 2. 非小細胞肺癌 : 局部晚期或轉移性非小細胞肺癌 3. 前列腺癌 : 於荷爾蒙治療失敗之轉移性前列腺癌 4. 頭頸癌 : 限局部晚期且無遠端轉移之頭頸部鱗狀細胞癌且無法手術切除者, 與 cisplatin 及 5-fluorouracil 併用, 作為放射治療前的引導治療, 限使用 4 個療程 (100/1/1) PRODUCT INFORMATION 7,8 Drug name Brand name Strength Herceptin 賀癌平凍晶注射劑 440 mg/vial Taxotere Injection 剋癌易注射劑 20 mg/vial ( 附 solvent) 80 mg/vial ( 附 solvent) Drug name Reconstitution & stability Dilution & stability Solvent Conc. Room temp. 2~8 Diluent Room temp. 2~8 20 ml BSWI 21 mg/ml -- 28 days NS -- 24 hr 附 (13% ethanol in water for injection) 10 mg/ml 8 hrs 8 hrs NS, D5W (to 0.3-0.74 mg/ml) 4 hrs -- BSWI: bacteriostatic water for injection PATIENT INFORMATION 4,5 一般注意事項 : 參見 化學治療一般注意事項 特殊注意事項 用於治療有症狀的心臟衰竭 高血壓病史或冠狀動脈疾病的病人時要格外小心, 尤其是先前已接受過 anthracycline 和 cyclophosphamide, 需先經過心臟功能基本標準評估

HD p5 藥物輸注過敏反應 : 在給藥前, 醫師會給予多種抗過敏藥物預防 但還是有少數病人在輸注時, 仍然發生過敏現象, 如胸悶 吸不到氣 皮膚疹 休克 如有任何不舒服, 請馬上通知醫護人員 藥物輸注時, 可能會發生不正常的心電圖變化 低血壓或心律不整, 需要停藥 等身體恢復正常後, 只要降低輸注藥物速度, 這些副作用大多會消失 通常白血球會在給藥後的第 5-9 天達到最低, 導致免疫力降低, 增加感染的危險 如果有任何感染的症狀如發燒, 打顫, 咳嗽, 喉嚨痛等, 請盡速就醫 也會造成血小板減少及貧血的現象, 要注意身上是否有小紫斑, 或小出血點 可能會較容易感到疲勞 可能造成喘或腳腫 醫師為預防此副作用, 會依情況處方類固醇來降低體液在身上的滯留 如有喘不過氣或嚴重的水腫, 請告訴您的醫師或護理師 手足症候群的治療 : 避免長時間熱水泡澡或洗碗 化學治療時, 手腳泡冰冷水, 會降低發生率與疼痛 REFERENCES 1. Marty M, Cognetti F, Maraninchi D, et al. Randomized Phase II Trial of the Efficacy and Safety of Combined With in Patients With Human Epidermal Growth Factor Receptor 2 Positive Metastatic Breast Cancer Administered As First-Line Treatment. J Clin Oncol. 2005;23(19):4265-74 2. Basch E, Prestrud AA, Hesketh PJ, et al. American Society of Clinical Oncology. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011; 29(31):4189-98. 3. National Comprehensive Cancer Network. NCCN clinical practice guidelines. Antiemesis. V.1.2013. NCCN website. http://www.nccn.org. Accessed August 20, 2013. 4. Micromedex Healthcare Series Web site. http://www.micromedexsolutions.com. Accessed August 20, 2013. 5. UpToDate Web site. http://www.uptodate.com. Accessed August 20, 2013 6. Piccart-Gebhart MJ, Procter M, Leyland-Jones B, et al. after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med. 2005 Oct 20;353(16):1659-72. 7. Taxotere [package insert]. England, Aventis Pharma 賽諾飛安萬特股份有限公司 ; 2006. 8. Herceptin [package insert]. California USA: F. Hoffmann-La Roche Ltd. 2005.