Drug Therapy

肺癌基本上分成小細胞及非小細胞兩大類。小細胞肺癌分成促限性及廣泛性兩期，除

了鄰近的淋巴腺轉移外，其他位置的淋巴結或器官的轉移都屬於廣泛性；對廣泛性的

小細胞肺癌治療以全身性化學治療為主，目前的第一線用藥是以Cisplatin+VP-16為主，

若對第一線藥物治療反應不佳，目前可以選擇的藥物包括

Cyclophosphamide+Doxorubicin+Vincristine(CAV)、Paclitaxel以及較新的CPT-11、Docetaxel、

Gemcitabine、Navelbine等，都有人嘗試。

而非小細胞肺癌轉移到遠處淋巴結或其他器官，是屬於第四期的疾病，目前第一線治療

的藥物是Gemcitabine+Cisplatin，而新藥如Paclitaxel、Docetaxel、Vinorelbine及Irinotecan等，

對於某些使用第一線藥物，病程仍持續進展之病人，仍具有一定的控制作用(單一藥物

使用時反應率約在20~30%不等)。

[資料來源]財團法人長庚紀念醫院全球資訊網

                  肺癌病友暨家屬關懷團體衞教網站

[資訊來源]肺癌病友暨家屬關懷團體衞教網站

                  台南護專

資料來源：肺癌病友暨家屬關懷團體衞教網站

                     禮來公司

Paclitaxel合併Carboplatin與Paclitaxel合併Gemcitabine

用於治療末期非小細胞肺癌的比較：第三期的隨機試驗

目的：
此項隨機性的研究用於比較paclitaxel合併carboplatin(PC)與paclitaxel合併gemcitabine(PG) 

兩種療法對於末期非小細胞肺癌的毒性和活性。

方法：
未做過化療的病患，在第1天皆給予paclitaxel 200 mg/m2，接著隨機選取一部份病患在

第1天給予濃度時間曲線面積（AUC）為6的carboplatin(A組)；另一組則在第1天及第8

天分別給予1000 mg/m2的gemcitabine(B組)，A、B兩組皆以每三個星期為一週期。另外，

利用student's t test進行這兩個獨立性樣本有關的回溯性成本分析。

結果：
全部有509位病患加入實驗（A組-252位；B組-257位），兩組病患所具有的特徵都相

當接近。A組存活期的中位數為10.8個月（95%信賴區間，存活期分佈從8.8到12個月）；

B組為9.8個月（95%信賴區間，8.0-11.7個月）（P=0.32）。一年的存活率分別是A組-41.7%，

B組-41.4%。A組反應率28.0%(完全反應的占有2%，部分反應26%) (95%信賴區間，

反應率從22%-34%)，B組為35%(完全反應占有5%，部分反應30%)（95%信賴區間，

反應率從29%-41%）（P=0.12）。毒性的反應輕微。發生3/4級的中性球減少症在A組、

B組分別為15%、15%；3/4級的血小板減少症分別為2%、1%；3/4級貧血則各為5%、2%。

平均整體成本分析（包括門診診治費及化療藥物的費用），A組（?7,612.64英鎊）和B

組（?7,484.77英鎊）間的差異不具統計上的意義（P<0.66）。

結論：
在治療末期非小細胞肺癌的研究上，PG和PC兩種治療方法的活性與耐受度是相同的。

Effects of Matuzumab in Combination With Pemetrexed for the Treatment of Advanced Lung Cancer

Purpose

This study is planned to answer questions about how the drug, matuzumab (EMD 72000), works and is part of an effort aimed to develop better treatment for advanced lung cancer by combining matuzumab, a monoclonal antibody, with a chemotherapy treatment, called pemetrexed. Pemetrexed is commercially available and has been approved for treatment of locally advanced or metastatic non-small cell lung cancer that could not be successfully treated with other chemotherapy.

The study aims to examine how non-small cell lung cancer (NSCLC) responds to matuzumab in combination with pemetrexed, as compared with giving pemetrexed alone. The study also aims to examine how safe and effective matuzumab is and for how long it stays in the body (pharmacokinetics). Matuzumab is an experimental treatment which is currently only available for research studies.

Study Type: Interventional
Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Official Title: Randomized, Phase II,Open-Label Controlled Study of Two Different Doses and Schedules of EMD 72000 (Matuzumab) in Combination With Pemetrexed, or Pemetrexed Alone, as Second-Line Treatment for Stage IIIB/IV Non-Small Cell Lung Cancer and Progressive Disease on or After First-Line Treatment With a Platinum in Combination With Taxanes, Gemcitabine and Vinorelbine

Further study details as provided by EMD Pharmaceuticals:

Expected Total Enrollment:  150

Study start: May 2005;  Expected completion: March 2007

Primary objective:

·         To determine the tumor response rate (as assessed by the Independent Review Committee [IRC]) of 2 different regimens of matuzumab in combination with pemetrexed in comparison to pemetrexed alone in subjects with stage IIIB/IV non-small cell lung cancer (NSCLC)

Secondary objectives:

The secondary objectives of this study are to determine the following:

·         Tumor response rate (as assessed by the Investigator)

·         Overall survival

·         Time to tumor progression

·         Duration of response

·         Safety and tolerability

·         Quality of life (QoL)

Additional objectives:

Additional objectives of this study include evaluation of:

·         Human antihumanized antibody (HAHA)

·         Pharmacokinetics (PK) of matuzumab

·         Epidermal growth factor receptor (EGFR) mutation analysis and association of EGFR mutations with tumor response

An open-label, randomized, controlled phase II study of matuzumab at a dose of 800 mg every week or 1600 mg every 3 weeks administered intravenously in combination with a fixed dose of pemetrexed (500 mg/m2 every 3 weeks intravenously), in comparison to pemetrexed alone, as a second-line treatment in subjects with Stage IIIB/IV NSCLC and progressive disease on or after first-line chemotherapy with a platinum analogue in combination with either taxanes, gemcitabine or vinorelbine.

Randomization will be performed in a stratified manner by the following factors:

·         Best response to first-line chemotherapy (complete response [CR]/partial response [PR]/stable disease [SD] versus progressive disease [PD])

·         Time from completion of previous chemotherapy to randomization (<3 months versus ≥3 months)

Subjects will be centrally randomized in a ratio of 1:1:1 as follows:

·         Group A: pemetrexed alone (500 mg/m2 every 3 weeks)

·         Group B: pemetrexed (every 3 weeks) plus matuzumab 800 mg every week

·         Group C: pemetrexed (every 3 weeks) plus matuzumab 1600 mg every 3 weeks

Subjects will be evaluated for tumor response every 6 weeks (regardless of treatment delays) until PD. An IRC will conduct a blinded review of the computed tomography (CT) and/or magnetic resonance imaging (MRI) results to determine response and response duration. Response will be classified according to the modified criteria of the World Health Organization (WHO). The IRC assessments will be used for the primary statistical analyses.

The Lung Cancer Symptom Scale (LCSS) will be used to assess changes in QoL. EGFR mutation analysis will be conducted on archived tumor material. Blood samples will be taken for HAHA (Groups B and C only). Matuzumab peak and trough concentrations will be measured at each matuzumab infusion (Groups B and C only).