本帖最后由 kangaizhixin 于 2013-4-18 13:15 编辑
Avastin+托普替康: 试验结果总结是对复发性小细胞肺癌，合用两种药物治疗，将病人在三个月内的治疗和其他传统治疗组对比。结果展示：用Avastin+托普替康治疗组的对癌症的控制效果比其他组要高出40%并抑制病情的进展。详情见下文。
Outcome Measures
Hide All Outcome Measures
1.Primary: Percentage of Participants With Progression-free Survival (PFS) at 3 Months [ Time Frame: 3 months ]
Measure Type Primary
Measure Title Percentage of Participants With Progression-free Survival (PFS) at 3 Months
Measure Description PFS = time from initiation of drug to time of first disease progression/death due to any cause. Progression assessed using Response Evaluation Criteria (RECIST): >=20% increase in sum of longest diameter (LD) of target lesions, taking as reference the smallest sum LD recorded since treatment started, or appearance of new lesion(s). If participant did not progress or die, the time of initiation of post-treatment anti-cancer therapy or time of last contact used. PFS at 3 months calculated by taking the Kaplan-Meier (KM) estimate at 90 days from the initiation of treatment. SE = standard error.
Time Frame 3 months
Safety Issue No
Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent-to-Treat (ITT) Population: all participants who received at least one dose of study medication
Reporting Groups
Description
Topotecan and Bevacizumab Participants were to receive oral topotecan 2.3 milligrams (mg)/meters squared (m^2)/day for 5 consecutive days (Days 1 to 5) and intravenous (IV) bevacizumab 15 mg/kilograms (kg) on Day 1 of each 21-day cycle. Treatment was to be continued for up to 8 cycles (a minimum of 4 cycles was recommended) or until disease progression or development of unacceptable toxicity, whichever occurred first. Prior approval from GlaxoSmithKline’s study physician was needed for participants who required treatment beyond 8 cycles.
Measured Values
Topotecan and Bevacizumab
Number of Participants Analyzed
50
Percentage of Participants With Progression-free Survival (PFS) at 3 Months
65
Statistical Analysis 1 for Percentage of Participants With Progression-free Survival (PFS) at 3 Months
Groups Topotecan and Bevacizumab
Method Z statistic
P Value 0.017
Greenwood variance 65.0
Standard Error of the mean ± 7.07
95% Confidence Interval ( 49.3 to 76.9 )
Additional details about the analysis, such as null hypothesis and power calculation:
No text entered.
Other relevant information, such as adjustments or degrees of freedom:
Z statistic was used to reject the null hypothesis provided Z>=1.65, where Z = (KM estimate at 3 months – null hypothesis value )/Greenwood SE.
Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
Historical data in target population showed 3-month PFS rates of <=50%. Oral topotecan with IV bevacizumab would provide clinically meaningful improvement in 3-month PFS。It demonstrated an over 40% improvement relative to the historical data.
Other relevant estimation information:
No text entered.
感谢楼主！您非常专业，希望以后有问题能多向您请教。
Avastin+托普替康提高有效率……二线的好消息啊。
肺癌让患者一个接一个痛苦倒下的主要原因并非是原发肺部病灶 （除整个肺部占位性病变外）。究其根本原因是肺癌继发性的转移：象脑，骨，肝和肾上腺等。最终造成这些脏器的功能衰竭，当然最终也包括肺。。。。。。 因此在治疗时，不管是在哪期，用哪线的药物，早期加上防止肺癌细胞转移的药物，患者都会为此而受益和减少痛苦的。同时也能相应地延缓和控制病情的恶化。。。。。。
kangaizhixin 发表于 2013-4-19 08:27 static/image/common/back.gif
肺癌让患者一个接一个痛苦倒下的主要原因并非是原发肺部病灶 （除整个肺部占位性病变外）。究其根本原因是肺 ...
已经全身转移了，也知道预后不好，只有治一步算一步，不知道怎么办。
kangaizhixin 发表于 2013-4-17 15:20 static/image/common/back.gif
例举的两个案例都是联合治疗小细胞癌的：一个用BAY1000394+铂类或依托泊苷; 另一个是Avastin+托普替康。 ...
请教 针对肺癌 砒霜联合其他药物有做人体试验了吗砒霜针对急性白血病的治疗 已经很成熟了 而且香港也开发了砒霜口服液 更方便了 其他肿瘤 特别是肺癌 有进展了吗？希望分享， 谢谢
啊呀AYA 发表于 2013-4-20 20:04 static/image/common/back.gif
请教 针对肺癌 砒霜联合其他药物有做人体试验了吗砒霜针对急性白血病的治疗 已经很成熟了 而且香港也开 ...
砒霜的主要成分是三氧化二砷，目前主要用来治疗急性早幼粒细胞白血病（AML）。现在正在美国Emory University 医学中心做临床试验用来治疗小细胞肺癌。据研究显示：三氧化二砷可以诱导低分化的癌细胞（可能属于癌症干细胞）成熟，然后再杀死此类细胞。据此，我理解由于小细胞肺癌从形态上多见未分化形，非常接近癌症干细胞。用三氧化二砷诱导这类小细胞先成熟再杀灭对转移肺癌细胞的控制和清剿可能会有帮助，特别是对骨转移会有益处。上述纯属我个人观点，仅供参考。下面附上相关文献以便阅读和祥查。
Arsenic trioxide is highly cytotoxic to small cell lung carcinoma cellsHelen M. Pettersson1, Alexander Pietras1, Matilda Munksgaard Persson1, Jenny Karlsson1, Leif Johansson2, Maria C. Shoshan3 and Sven Påhlman1
+ Author Affiliations
1Center for Molecular Pathology, CREATE Health and 2Division of Pathology, Department of Laboratory Medicine, Lund University, University Hospital MAS, Malmö, Sweden; and 3Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska Institute and Hospital, Stockholm, Sweden
Requests for reprints: Helen Pettersson, Center for Molecular Pathology, Department of Laboratory Medicine, Lund University, University Hospital MAS, Entrance 78, SE-205 02 Malmö, Sweden. Phone: 46-40-332285; Fax: 46-40-337063. E-mail: helen.pettersson@med.lu.se
Abstract
Small cell lung carcinoma (SCLC) is an extremely aggressive form of cancer and current treatment protocols are insufficient. SCLC have neuroendocrine characteristics and show phenotypical similarities to the childhood tumor neuroblastoma. As multidrug-resistant neuroblastoma cells are highly sensitive to arsenic trioxide (As2O3) in vitro and in vivo, we here studied the cytotoxic effects of As2O3 on SCLC cells. As2O3 induced pronounced cell death in SCLC cells at clinically relevant concentrations, and also at hypoxia. SCLC cells were more sensitive than non–SCLC cells to As2O3. Cell death was mainly due to necrosis, although apoptotic responses were also seen. A significant in vivo effect of As2O3 on SCLC growth was shown in a nude mice-xenograft model, although a fraction of the treated tumor-bearing animals did not respond. The nonresponding SCLC tumors differed in morphology and cell organization compared with treatment-responsive tumors, which in turn, showed decreased vascularization and higher expression of neuroendocrine markers compared with control tumors. Our results suggest a potential clinical application of As2O3 in SCLC therapy. In addition to cell death induction, antiangiogenic induction of differentiation may also be part of the in vivo effect of As2O3 on SCLC growth, as suggested by an increase in neuroendocrine markers in cultured cells.
»
ClinicalTrials.gov BackgroundAbout the Results DatabaseHistory, Policies, and LawsMedia/Press ResourcesLinking to This SiteTerms and ConditionsDisclaimerText Size
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Study of Arsenic Trioxide in Small Cell Lung CancerThis study is currently recruiting participants.
Verified November 2012 by Emory University
Sponsor:
Emory University
Collaborator:
Cephalon
Information provided by (Responsible Party):
Taofeek K. Owonikoko, Emory UniversityClinicalTrials.gov Identifier:
NCT01470248
First received: October 25, 2011
Last updated: November 15, 2012
Last verified: November 2012
History of Changes Full Text View Tabular ViewNo Study Results PostedDisclaimerHow to Read a Study RecordPurpose
The purpose of this study is to study the effect of an anticancer drug, Arsenic Trioxide, in patients with small cell lung cancer who have failed at least one standard chemotherapy regimen as well as patients who are unable to tolerate the standard treatment for their cancer. The investigators seek to establish the safety of and efficacy of Arsenic Trioxide in this patient group. The study will include up to 36 participants with small cell lung cancer.
The investigators want to find out what effects, good or bad, that the study drug has on your cancer. This study will also look at specific biomarkers in your blood and in the tumor tissue which may help the investigators to determine if the levels of these biomarkers are related to tumor response to treatment.
Arsenic Trioxide, also known by the brand name, Trisenox, is a chemotherapy drug approved by the Food and Drug Administration (FDA) for the treatment of a specific type of blood cancer called Acute Promyelocytic Leukemia. It works in part by making cancer cells become more mature thereby stopping them from growing in number and more likely to die off.
ConditionInterventionPhase
Lung Cancer
Cancer of Lung
Pulmonary Cancer
Pulmonary Neoplasms
Carcinoma, Small Cell
Drug: Arsenic Trioxide
Phase 2
Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Single Arm, Two-Stage Phase II Study of Arsenic Trioxide in Previously Treated Small Cell Lung Cancer
Resource links provided by NLM:
MedlinePlus related topics: Arsenic Cancer Lung Cancer
Drug Information available for: Arsenic trioxide Arsenic
U.S. FDA Resources
Further study details as provided by Emory University:
Primary Outcome Measures:
•Response rate (RR) [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
•Clinical Benefit Rate (CBR) [ Time Frame: After completing at least 1 cycle (8 weeks) of treatment ] [ Designated as safety issue: No ]
Sum of CR, PR and SD in patients eligible for efficacy analysis.
Secondary Outcome Measures:
•Progression-free survival [ Time Frame: Every 8 weeks ] [ Designated as safety issue: No ]
•Overall Survival [ Time Frame: From enrolment till death on average up to 2 years ] [ Designated as safety issue: No ]
Duration of time from enrollment on study until death
Estimated Enrollment: 36
Study Start Date: August 2011
Estimated Study Completion Date: August 2014
Estimated Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
ArmsAssigned Interventions
Experimental: Arsenic Trioxide Treatment
This is a single arm study. All patients will be treated with the investigational agent, Arsenic Trioxide, according to the dose and schedule indicated in the protocol. Drug: Arsenic Trioxide
Drug will be given as a loading dose of 0.32mg/kg/day for 4 days in Week 1, followed by 0.25mg/kg/day twice per week for 5 weeks, followed by 2 weeks of rest, at which time response assessment will be performed. Patients will be restaged prior to the beginning of a new cycle, every 2 months on average. Maximum of 6 cycles of therapy will be administered in the absence of tumor progression or excessive side effectsOther Names:
•Trisenox
•ATO
Eligibility
Ages Eligible for Study: 18 Years and older
Genders Eligible for Study: Both
Accepts Healthy Volunteers: No
Criteria
Inclusion Criteria:
•Patients must have histologically or cytologically confirmed small cell lung cancer
•Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as >20 mm with conventional techniques or as >10 mm with spiral CT scan. See Section 11 for the evaluation of measurable disease.
•Patient must have failed or found to be intolerant of standard frontline platinum-based regimens. There is no limit on the number of prior regimens provided the patient meets all the other eligibility criteria.
•Adult patients 18 years or older. Because no dosing or adverse event data are currently available on the use of arsenic trioxide in patients <18 years of age, children are excluded from this study but will be eligible for future pediatric single-agent trials, if applicable.
•Life expectancy of greater than 3 months
•ECOG performance status of 0,1 or 2
•Patients must have normal organ and marrow function as defined below:
•absolute neutrophil count >1,500/mL
•platelets >100,000/mL
•total bilirubin ≤ 1.5 X institutional upper limits of normal
•AST(SGOT)/ALT(SGPT) <2.5 X institutional upper limit of normal
•creatinine ≤ 1.5 X institutional upper limits of normal OR
•creatinine clearance >40 mL/min/1.73 m2 for patients with
•creatinine levels above institutional normal.
•Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential
•Ability to understand and the willingness to sign a written informed consent document.
•No history of QTc prolongation syndrome or any other cardiac conduction abnormality evidenced by normal baseline EKG (QTc ≤450 in males and ≤470 in females)
•Both men and women and members of all races and ethnic groups are eligible for this trial.
Exclusion Criteria:
•Need for treatment with chemotherapy (within 4 weeks; 6 weeks for nitrosoureas or mitomycin C); radiotherapy or biologic agents (within 2 weeks) prior to entering the study or those who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
•Patients may not be receiving any other investigational agents.
•Patients with uncontrolled symptomatic brain metastases. Patients with no known brain metastasis are not required to undergo screening prior to enrolment.
•History of allergic reactions attributed to compounds of similar chemical or biologic composition to arsenic trioxide.
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
•Pregnant women are excluded from this study because Trisenox is a category D agent with the potential to cause fetal harm. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with Trisenox, breastfeeding should be discontinued if the mother is treated with Trisenox.
•HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with Trisenox. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy. Appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated.
•Patients who require ongoing treatment with any hematopoietic colony-stimulating growth factors (e.g., G-CSF, GM-CSF) ≤ 2 weeks prior to starting study drug.
•Patients who are currently receiving treatment with medication that has the potential to prolong the QT interval or inducing Torsades de Pointes and the treatment cannot either be discontinued or switched to a different medication prior to starting study drug
•Patients who have undergone major surgery ≤ 2 weeks prior to starting study drug or who have not recovered from side effects of such therapy
•History of another malignancy within 3 years, except curatively treated basal cell carcinoma of the skin, DCIS, early stage prostate cancer without detectable PSA or excised carcinoma in situ of the cervix
•Patient is unable or unwilling to abide by the study protocol
Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01470248
Contacts
Contact: Taofeek Owonikoko, MD, PhD 1-888-946-7447 towonik@emory.edu
Locations
United States, Georgia
Emory University Winship Cancer Institute Recruiting
Atlanta, Georgia, United States, 30322
Contact: Taofeek Owonikoko, MD, PhD 888-946-7447 towonik@emory.edu
Sponsors and Collaborators
Emory University
Cephalon
Investigators
Principal Investigator: Taofeek Owonikoko, MD, PhD Emory University Winship Cancer Institute
More Information
Additional Information:
Winship Clinical Trials
No publications provided
Responsible Party: Taofeek K. Owonikoko, Assistant Professor, Hematology/Medical Oncology, Principal Investigator, Emory University
ClinicalTrials.gov Identifier: NCT01470248 History of Changes
Other Study ID Numbers: WCI1988-11
Study First Received: October 25, 2011
Last Updated: November 15, 2012
Health Authority: United States: Institutional Review Board
Keywords provided by Emory University:
Lung Cancer
Carcinoma, small cell
Trisenox
Arsenic trioxide
phase II trial
Additional relevant MeSH terms:
Neoplasms
Carcinoma
Lung Neoplasms
Small Cell Lung Carcinoma
Carcinoma, Small Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Arsenic trioxide
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
ClinicalTrials.gov processed this record on April 16, 2013
kangaizhixin 发表于 2013-4-21 09:51 static/image/common/back.gif
砒霜的主要成分是三氧化二砷，目前主要用来治疗急性早幼粒细胞白血病（AML）。现在正在美国Emory Univers ...
嗯，我家就是未分化的。
但是砒霜……还真是不敢试啊。
现在纠结于是否放疗，兄有时间帮看下……
http://www.51qiji.com/forum.php?mod=viewthread&tid=36493&highlight=
谢谢楼主可惜不是中文有的看不太懂