复旦大学：《循证医学》课程教学资源（预习资料）临床实践指南预习.pdf

Unit 10：临床实践指南主讲教师：王小钦助理教师：陈波斌授课时间：2010 年 4 月 27 日（1 班）；2010 年 4 月 30 日（2 班）一、教学目的：掌握和熟悉临床实践指南的应用原则和方法二、教学内容： 1. 掌握临床实践指南的基本概念、推荐意见的证据级别、评价原则和应用原则 2. 熟悉临床实践指南的检索方法 3. 了解临床实践指南的制定步骤三、教学重点：实践指南的推荐意见的证据级别四、教学难点：实践指南的评价原则五、中文和英文关键词临床实践指南 Clinical Practice Guidelines 推荐意见 Recommendations 证据等级 Levels of evidence 六、阅读文献：请上网查询 2 个指南，并阅读 1、American Society of Clinical Oncology 2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline (http://www.asco.org) 2、Prevention and treatment of cancer-related infections (http://www.nccn.org) 七、讨论思考题：（一）临床病例：肿瘤化疗后白细胞减少，发热感染的病史资料。 1. 患者，女性，31 岁，公司职员 2. 系发现皮肤瘀点、瘀斑一周而入院。患者 2009 年 1 月 8 日无意中发现双下肢瘀点、瘀斑，2 天后发展至足背，伴有牙龈出血，就诊我科门诊，查血常规：WBC：243.13×109 /L，中性粒细胞 6%，淋巴细胞 5%，单核细胞 1%，异常细胞 88%，Hb 98g/L，Plt 32×109 /L，为进一步诊治而入院。患者在半年前体检血常规正常。 3. 入院体检：消瘦，贫血貌，四肢、躯干部可见多处瘀点、瘀斑，以双下肢明显，胸骨中下端有明显触痛，双侧颈部、左侧腋下可及多枚黄豆大小淋巴结，活动度可，余浅表淋巴结未扪及肿大，颈软，两肺呼吸音清，未闻及啰音， HR 90 次/分，各瓣膜区未闻及杂音，肝脏肋缘下平脐，脾脏肋缘下 3 指，质地中等，无压痛，双下肢无水肿。第 216 页

VOLUME 24 NUMBER 19 JULY 1 2006 JOURNAL OF CLINICAL ONCOLOGY A SCO SPECIAL ARTICLE 2006 Update of Recommendations for the use of white Blood Cell growth Factors: An Evidence-Based Clinical Practice guideline Thomas/ Smith( Chair), James Khatcheressian, Gary H. Lyman, Howard Ozer, James O. Armitage Lodovico Balducci, Charles L. Bennett, Scott B. Cantor, Jeffrey Crawford, Scott /. Cross, George Demetri, Christopher E. Desch, Philip A. Pizzo, Charles A. Schiffer, Lee Schwartzberg, Mark R. Somerfield, George Somlo James C. Wade, James L. Wade, Rodger /. Winn, Antoinette J. Wozniak, and Antonio C. Wolf From the American Society of Cinical A B S TRA C T Submitted March 14, 2006; accepted March 24. 2006 To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic Authors disclosures of potential con- colony-stimulating factors (CSF) cts of interest and author contribu- ions are found at the end of this The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASco clinical outcomes criteria, the Update ociety of Clinical Oncology, Cancer Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness Street. Suite 200. Alexandria, VA Recommendations 22314: e-mail: guidelines@asco.org The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia(FN) is an 0 2006 by American Society of Clinical important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of fN is approximately 20% and no other equally effective regimen that does not 0732-183X06/24193187/2000 require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose- intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of cSF or pegylated G-CSF J Clin Oncol 24: 3187-3205 2006 by American Society of Clinical Oncology INTRODUCTION The Update Committee had four face-to-face neetings to consider the evidence for each of the The American Society of Clinical Oncology 2005 Recommendations. The guideline was circu- (ASCO) published its first evidence-based clinical lated in draft form to the Update Committee for practice guideline in 1994 on the use of hemato- review and approval. ASCOs Health Services Com poietic colony-stimulating factors(CSF). An Up- mittee and the ASCO Board of Directors also re date Committee of the original Expert Panel viewed the final document. updated this guideline in 1996, 1997, and 2000 (It is important to emphasize that guidelines For the 2005 update, an Update Committee com- and technology assessments cannot always account posed of members from the full Panel and selected for individual variation among patients. They are ad hoc members was formed to complete the re- not intended to supplant physician judgment with view and analysis of data published since the 2000 respect to particular patients or special clinical situ Update. A series of computerized literature ations, and cannot be considered inclusive of all searches of MEDLINE and the Cochrane Library proper methods of care or exclusive of other treat- was performed. Details of the searches are re- ments reasonably directed at obtaining the same ported in Appendix A result. Accordingly, ASCO considers adherence to

2006 Update of Recommendations for the Use of White Blood Cell Growth Factors: An Evidence-Based Clinical Practice Guideline Thomas J. Smith (Chair), James Khatcheressian, Gary H. Lyman, Howard Ozer, James O. Armitage, Lodovico Balducci, Charles L. Bennett, Scott B. Cantor, Jeffrey Crawford, Scott J. Cross, George Demetri, Christopher E. Desch, Philip A. Pizzo, Charles A. Schiffer, Lee Schwartzberg, Mark R. Somerfield, George Somlo, James C. Wade, James L. Wade, Rodger J. Winn, Antoinette J. Wozniak, and Antonio C. Wolff ABSTRACT Purpose To update the 2000 American Society of Clinical Oncology guideline on the use of hematopoietic colony-stimulating factors (CSF). Update Methodology The Update Committee completed a review and analysis of pertinent data published from 1999 through September 2005. Guided by the 1996 ASCO clinical outcomes criteria, the Update Committee formulated recommendations based on improvements in survival, quality of life, toxicity reduction and cost-effectiveness. Recommendations The 2005 Update Committee agreed unanimously that reduction in febrile neutropenia (FN) is an important clinical outcome that justifies the use of CSFs, regardless of impact on other factors, when the risk of FN is approximately 20% and no other equally effective regimen that does not require CSFs is available. Primary prophylaxis is recommended for the prevention of FN in patients who are at high risk based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. CSF use allows a modest to moderate increase in dose-density and/or dose-intensity of chemotherapy regimens. Dose-dense regimens should only be used within an appropriately designed clinical trial or if supported by convincing efficacy data. Prophylactic CSF for patients with diffuse aggressive lymphoma aged 65 years and older treated with curative chemotherapy (CHOP or more aggressive regimens) should be given to reduce the incidence of FN and infections. Current recommendations for the management of patients exposed to lethal doses of total body radiotherapy, but not doses high enough to lead to certain death due to injury to other organs, includes the prompt administration of CSF or pegylated G-CSF. J Clin Oncol 24:3187-3205. © 2006 by American Society of Clinical Oncology INTRODUCTION The American Society of Clinical Oncology (ASCO) published its first evidence-based clinical practice guideline in 1994 on the use of hematopoietic colony-stimulating factors (CSF). An Update Committee of the original Expert Panel updated this guideline in 1996, 1997, and 2000. For the 2005 update, an Update Committee composed of members from the full Panel and selected ad hoc members was formed to complete the review and analysis of data published since the 2000 Update. A series of computerized literature searches of MEDLINE and the Cochrane Library was performed. Details of the searches are reported in Appendix A. The Update Committee had four face-to-face meetings to consider the evidence for each of the 2005 Recommendations. The guideline was circulated in draft form to the Update Committee for review and approval. ASCO’s Health Services Committee and the ASCO Board of Directors also reviewed the final document.* (*It is important to emphasize that guidelines and technology assessments cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments reasonably directed at obtaining the same result. Accordingly, ASCO considers adherence to From the American Society of Clinical Oncology, Alexandria, VA. Submitted March 14, 2006; accepted March 24, 2006. Authors’ disclosures of potential con- flicts of interest and author contributions are found at the end of this article. Address reprint requests to American Society of Clinical Oncology, Cancer Policy and Clinical Affairs, 1900 Duke Street, Suite 200, Alexandria, VA 22314; e-mail: guidelines@asco.org. © 2006 by American Society of Clinical Oncology 0732-183X/06/2419-3187/$20.00 DOI: 10.1200/JCO.2006.06.4451 JOURNAL OF CLINICAL ONCOLOGY ASCO SPECIAL ARTICLE VOLUME 24 NUMBER 19 JULY 1 2006 3187 Copyright © 2006 by the American Society of Clinical Oncology. All rights reserved. Information downloaded from jco.ascopubs.org and provided by charlesworth on August 12, 2009 from 202.120.79.222. 第 218 页

this technology assessment to be voluntary, with the ultimate deter- the chemotherapy regimen. For"dose dense"regimens, CSEs are mination regarding its application to be made by the physician in light required and recommended New clinical trial data support the use of of each patients individual circumstances. In addition, this technol- CSF when the risk of FN is in the range of approximately 20%or ogy assessment describes the use of procedures and therapies in clini- higher. The use of regimens, if available, that do not require CSFs cal practice; it cannot be assumed to apply to the use of these because of equal efficacy and lower risk of FN remains standard med interventions performed in the context of clinical trials, given that ical practice. In the absence of special circumstances, most commonly clinical studies are designed to evaluate or validate innovative ap- used regimens have risks of fN of less than 20%(Table 1). In making proaches in a disease for which improved staging and treatment is the decision to use prophylactic CSF or not, oncologists should con needed. In that guideline and technology assessment development sider not only the optimal chemotherapy regimen, but also the indi involve a review and synthesis of the latest literature, a practice guide- vidual patient risk factors and the intention of treatment; that is, line or technology assessment also serves to identify important ques- curative, prolongation of life, or symptom control and palliation. tions and settings for further research. Examples of appropriate use in the curative setting include adjuvant In this review, the Update Committee was guided by the 1996 treatment of early-stage breast cancer with more intensive regimens ASCO outcomes criteria that justify the use of a drug or technology, such as TAC or FEC100 or the use of CHOP or CHOP-like regimens and recommended therapy when compelling positive effects to those in older patients with aggressive non-Hodgkins lymphoma. utcomes was demonstrated. The 2005 Update Committee agreed Special circumstances. Clinicians may occasionally be faced with unanimously that reduction in febrile neutropenia was an important cinical patients who might benefit from relatively nonmyelosuppressive outcome that justified useof CSFs, regardless of impact on other factors, when chemotherapy but who have potential risk factors for febrile neut- the risk of febrile neutropenia(FN)was approximately 20% and no other ropenia or infection because of bone marrow compromise or equally effective regimen that did not require CSFs was available. comorbidity. It is possible that primary CSF administration may be exceptionally warranted in patients at higher risk for chemotherapy- SUMMARY OF RELEVANT BACKGROUND DATA induced infectious complications, even though the data supporting such use are not conclusive Certa in clinical factors predispose to increased complicat Myelotoxicity of Standard Chemotherapy Regimens from prolonged neutropenia, including: patient age greater than 65 benefits and risks. In 1996, the American Society of Clinical On- years: poor performance status; previous episodes of FN; extensive prior treatment including large radiation ports; administration of cology published a list of important clinical outcomes that justify combined chemoradiotherapy; cytopenias due to bone marrow in- the use of a technology or drug in the guideline development volvement by tumor; poor nutritional status; the presence of open process. The clinical outcomes include the following improve- wounds or active infections;, more advanced cancer, as well as other ments in overall or disease-free survival:; improvement in quality of serious comorbidities. In such situations, primary prophylaxis with life; reduced toxicity; and improved cost-effectiveness. Table 1 lists many common chemotherapeutic regimens cur CSF is often appropriate even with regimens with FN rates less than rently in use. Of note, unless these regimens meet or exceed the FN high-risk patients are most often excluded from clinical trials, and this risk threshold suggested in the specific guideline recommendations is not a situation likely to have additional clinical data. that follow, the regimens are usually administered without growth The special circumstances have always been part of ASCOs CSF factor support. Whenever possible, large clinical trials performed guidelines, in recognition that there are patient factors that predict for since the 2000 update are referenced. While this listing is not the rate and severity of febrile neutropenia. These special circum- all-inclusive, it incorporates some new treatment trends such as stances have been maintained from previous versions of the guideline dose-dense therapy Studies dealing with older patients have been There are no additional new data on patients with special circum- included to illustrate a growing interest in the treatment of older stances that predispose to high FN risk. The rate at which the use of cancer patients and concern regarding their tolerance for chemo- CSFs should be considered has changed from 40%to 20%,consis Table 1 documents the febrile neutropenia rates for common usual risk patient, 34. hat demonstrates efficacy in reducing therapy, and a special recommendation has been added for those tent with the new evidence t regimens in everyday use. It is not intended to be a definitive guide to therapy, but as a guide to FN rates. Healthcare providers may 2005 update wish to check the FN rate before prescribing CSFs. Clinical efficacy data. In some situations, primary prophylaxis with CSFs is essential and recommended to alleviate the toxicity of SPECIFIC RECOMMENDATIONS certain"dose dense"chemotherapy regimens. Dose dense regimens have demonstrated efficacy in the adjuvant treatment of breast cancer 1. Recommendations for Primary Prophylactic CSF and possible efficacy in the treatment of elderly patients with aggres Administration ( First and Subsequent-Cycle Use) sive lymphoma, based on one large trial. Two large randomized clinical trials have documented that the 2005 recommendations risk of FN may be reduced substantially by primary prophylaxis with General circumstances. Primary prophylaxis is recommended CSFs, when the risk of FN without CSFs is approximately 20%. Vogel for the prevention of FN in patients who have a high risk of fN based et al randomized 928 patients with metastatic breast cancer( 62%)or on age, medical history, disease characteristics, and myelotoxicity of in the adjuvant setting(38%)to receive or not to receive pegfilgrastim OURNAL OF CLINICAL ONCOLOGY Information downloaded from jco. ascopubs org and 33,阻 arlesworth on August 12, 2009 from 202. 120.79.222 Copyright 2006 by the American Society of Clinical Oncology. All rights reserved

this technology assessment to be voluntary, with the ultimate determination regarding its application to be made by the physician in light of each patient’s individual circumstances. In addition, this technology assessment describes the use of procedures and therapies in clinical practice; it cannot be assumed to apply to the use of these interventions performed in the context of clinical trials, given that clinical studies are designed to evaluate or validate innovative approaches in a disease for which improved staging and treatment is needed. In that guideline and technology assessment development involve a review and synthesis of the latest literature, a practice guideline or technology assessment also serves to identify important questions and settings for further research.) In this review, the Update Committee was guided by the 1996 ASCO outcomes criteria that justify the use of a drug or technology, and recommended therapy when compelling positive effects to those outcomes was demonstrated. The 2005 Update Committee agreed unanimouslythat reductioninfebrile neutropeniawas animportant clinical outcomethatjustified use ofCSFs, regardless ofimpact on otherfactors,when the risk of febrile neutropenia (FN) was approximately 20% and no other equally effective regimen that did not require CSFs was available. SUMMARY OF RELEVANT BACKGROUND DATA Myelotoxicity of Standard Chemotherapy Regimens The use of any technology or drug requires a balance of the benefits and risks. In 1996, the American Society of Clinical Oncology published a list of important clinical outcomes that justify the use of a technology or drug in the guideline development process.1 The clinical outcomes include the following: improvements in overall or disease-free survival; improvement in quality of life; reduced toxicity; and improved cost-effectiveness. Table 1 lists many common chemotherapeutic regimens currently in use. Of note, unless these regimens meet or exceed the FN risk threshold suggested in the specific guideline recommendations that follow, the regimens are usually administered without growth factor support. Whenever possible, large clinical trials performed since the 2000 update are referenced. While this listing is not all-inclusive, it incorporates some new treatment trends such as dose-dense therapy. Studies dealing with older patients have been included to illustrate a growing interest in the treatment of older cancer patients and concern regarding their tolerance for chemotherapy, and a special recommendation has been added for those over 65 years of age. Table 1 documents the febrile neutropenia rates for common regimens in everyday use. It is not intended to be a definitive guide to therapy, but as a guide to FN rates. Healthcare providers may wish to check the FN rate before prescribing CSFs. SPECIFIC RECOMMENDATIONS 1. Recommendations for Primary Prophylactic CSF Administration (First and Subsequent-Cycle Use) 2005 recommendations General circumstances. Primary prophylaxis is recommended for the prevention of FN in patients who have a high risk of FN based on age, medical history, disease characteristics, and myelotoxicity of the chemotherapy regimen. For “dose dense” regimens, CSFs are required and recommended. New clinical trial data support the use of CSF when the risk of FN is in the range of approximately 20% or higher.2,3 The use of regimens, if available, that do not require CSFs because of equal efficacy and lower risk of FN remains standard medical practice. In the absence of special circumstances, most commonly used regimens have risks of FN of less than 20% (Table 1). In making the decision to use prophylactic CSF or not, oncologists should consider not only the optimal chemotherapy regimen, but also the individual patient risk factors and the intention of treatment; that is, curative, prolongation of life, or symptom control and palliation. Examples of appropriate use in the curative setting include adjuvant treatment of early-stage breast cancer with more intensive regimens such as TAC or FEC100 or the use of CHOP or CHOP-like regimens in older patients with aggressive non-Hodgkin’s lymphoma. Special circumstances. Clinicians may occasionally be faced with patients who might benefit from relatively nonmyelosuppressive chemotherapy but who have potential risk factors for febrile neutropenia or infection because of bone marrow compromise or comorbidity. It is possible that primary CSF administration may be exceptionally warranted in patients at higher risk for chemotherapyinduced infectious complications, even though the data supporting such use are not conclusive. Certain clinical factors predispose to increased complications from prolonged neutropenia, including: patient age greater than 65 years; poor performance status; previous episodes of FN; extensive prior treatment including large radiation ports; administration of combined chemoradiotherapy; cytopenias due to bone marrow involvement by tumor; poor nutritional status; the presence of open wounds or active infections; more advanced cancer, as well as other serious comorbidities. In such situations, primary prophylaxis with CSF is often appropriate even with regimens with FN rates less than 20%. This was the consensus opinion of the expert committee. Such high-risk patients are most often excluded from clinical trials, and this is not a situation likely to have additional clinical data. The special circumstances have always been part of ASCO’s CSF guidelines, in recognition that there are patient factors that predict for the rate and severity of febrile neutropenia. These special circumstances have been maintainedfrom previous versions of the guideline. There are no additional new data on patients with special circumstances that predispose to high FN risk. The rate at which the use of CSFs should be considered has changed from 40% to 20%, consistent with the new evidence that demonstrates efficacy in reducing FN rates when the risk is approximately 20%, as noted above for usual risk patients.2,3 2005 update Clinical efficacy data. In some situations, primary prophylaxis with CSFs is essential and recommended to alleviate the toxicity of certain “dose dense” chemotherapy regimens. Dose dense regimens have demonstrated efficacy in the adjuvant treatment of breast cancer and possible efficacy in the treatment of elderly patients with aggressive lymphoma, based on one large trial.4 Two large randomized clinical trials have documented that the risk of FN may be reduced substantially by primary prophylaxis with CSFs, when the risk of FN without CSFs is approximately 20%. Vogel et al randomized 928 patients with metastatic breast cancer (62%) or in the adjuvant setting (38%) to receive or not to receive pegfilgrastim Smith et al 3188 JOURNAL OF CLINICAL ONCOLOGY Copyright © 2006 by the American Society of Clinical Oncology. All rights reserved. Information downloaded from jco.ascopubs.org and provided by charlesworth on August 12, 2009 from 202.120.79.222. 第 219 页

Table 1. Incidence of Hematologic and Infectious Toxicities Associated With Selected Chemotherapy Regimens Cancer Histology Stage and Prior Therapy Regimen No. of Patients Leukopenia (grade 4; %) Neutropenia (grade 4; %) Febrile Neutropenia (%) Fever (grade 2; %)‡ Infection (grade 3; %)§ Infectious Death (%) Adult AML84 Newly diagnosed Ara-C/DNR 163 93 — — 37 (no infection) 64 12 AIDS-related85-87 Advanced/1st and 2nd line Lipo Dox G(M)-CSF 133 36 (3 4) 6 — 1 0 Kaposi’s Sarcoma VP-16 (oral); 36; — 19.4; —— 8 — — — — — Paclitaxel 56 — 35 AIDS-related†88 Intermediate CHOP (modified) 40 — 25 (3 4) 2.5 — — 10 NHL High-grade, untreated CHOP G-CSF 25 — 13 (3 4) 0 — — Bladder89,90 Advanced, no prior systemic therapy GC 203 — 29.9 2 0 2.5 1 MVAC 202 — 65.2 14 3.1 15.1 2.5 Prior adjuvant allowed CBDCA/Pac G-CSF 33 — 21 21 — 1 patient, sepsis 0 Breast18,91-97 Adjuvant CA(60 mg/m2 ) 1060 — 62 10 (hospitalized) — 17 0 CA3T(all dose levels) 1590 — 16 3 — 11 0 CEF 351 49.9 89.7 8.5 — — 0 TAC 109 — — 23.8 — — — A3T3C 484 1 24 3 — 3 0 Adjuvant (dose dense) A3T3C G-CSF 493 — 3 2 — 4 0 AC3T 501 11 43 6 — 5 0 AC3T G-CSF 495 6 9 2 — 3 0 Metastatic (1st line) A (75) 165 — 77.8 12.3 — 4.3 1 death Doc (100) 161 — 78.6 5.7 — 2.5 1 death AC 215 — 88 (3 4) 10 — 2 0.5 AT 214 — 97 (3 4) 33 — 8 0 TAC 54 — 100 (3 4) 34 — 2 0 Metastatic (2nd line) CapDoc 255 — 11 16 — — 1 Doc 256 — 12 21 — — 0 Colorectal98-103 Adjuvant 5-FU/LV/L 449 2 — — — — 1 5-FU/LV 116 15 (high LV) — — — — 1.7 22 (low LV) Advanced IFL 189 — 24 7.1 — 1.8 1 FL 226 — 42.5 14.6 — 0 1.4 I 226 — 12.1 5.8 — 2.2 1 FOLFOX4 152 — 17 6 — — 0 FOLFIRI 145 20.4 (3 4) 28.8 (3 4) 9.3 — 1.9 1 Advanced (one prior chemo allowed) CPT-11 (350 mg/m2 Q3wk) 213 36 (3 4) 48 (3 4) 14 — 1 3 deaths Gastric104 Advanced ECF (infusion) 289 13 32 — 1 6 1 Germ cell105,106 Advanced BEP 141 — 34 — — —2 VIP 145 — 60 — — — 2.8 Relapsed VeIP 135 — — 71 — — 2.1 (all deaths) Head/neck107-109 Recurrent; metastatic 5-FU/CBDCA 86 2.3 1.2 — — — 1.2 CBDCA/Pac 41 4.9 9.8 — — — 2.4 Cis/Doc 36 — 71 6 — 11 0 Induction Cis/Doc/5-FU 43 — 95 (3 4) 19 — 2 0 Lung110-117 Extensive SCLC Cis/VP-16 159 14 38 — — 8 6 (all toxic deaths) No prior treatment CAV 156 28 52 — — 16 4 (all toxic deaths) CBDCA/VP-16 74 5 — — — — 2.6 Cis/CPT-11 77 4 25.3 — 1.3 5.3 3.7 Recurrent Topo 107 31.7 70.2 28 — 4.7 CAV 104 43.6 71.7 26 — 4.8 1 Advanced NSCLC Cis/VNR 206 — 59 10 — — 2 No prior treatment 1 Cis/Pac (24hr) 288 — 57 16 — 10 2 Cis/Gem 288 — 39 4 — 7 1 Cis/Doc 289 — 48 11 — 9 CBDCA/Pac 290 — 43 4 — 6 — CBDCA/Doc 406 49.5 (3 4) 74.4 (3 4) 3.7 — 11 — Recurrent (2nd line) Doc (75 mg/m2 ) 276 40.2 (3 4) — 12.7 — 3.3 Pemetrexed 265 5.3 (3 4) 1.9 — 0 (continued on following page) 2006 Recommendations for WBC Growth Factors www.jco.org 3189 Copyright © 2006 by the American Society of Clinical Oncology. All rights reserved. Information downloaded from jco.ascopubs.org and provided by charlesworth on August 12, 2009 from 202.120.79.222. 第 220 页