lunes, 18 de mayo de 2009
domingo, 17 de mayo de 2009
Phase II Randomized Controlled Trial of an Epidermal Growth Factor Vaccine in Advanced Non–Small-Cell Lung Cancer
Purpose We show the result of a randomized phase II clinical trial with an epidermal growth factor (EGF)-based cancer vaccine in advanced non–small-cell lung cancer (NSCLC) patients, evaluating immunogenicity, safety, and effect on survival.
Patients and Methods Eighty patients with stage IIIB/IV NSCLC after finishing first-line chemotherapy were randomly assigned to receive best supportive care or EGF vaccinations.
Results Vaccination was safe. Adverse events were observed in less than 25% of cases and were grade 1 or 2 according to National Cancer Institute Common Toxicity Criteria. Good anti-EGF antibody response (GAR) was obtained in 51.3% of vaccinated patients and in none of the control group. Serum EGF concentration showed a major decrease in 64.3% of vaccinated patients. GAR patients survived significantly more than those with poor antibody response (PAR). Also, patients whose serum EGF dropped below 168 pg/mL survived significantly more than the rest. There was a trend to an increased survival for vaccinated patients compared with controls. The survival advantage for vaccinated patients compared with controls was statistically significant in the subgroup of patients with age younger than 60 years.
Conclusion Vaccination with EGF was safe and provoked an increase in anti-EGF antibody titers and a decrease in serum EGF. There was a direct correlation between antibody response and survival. There was a direct correlation between decrease in serum EGF and survival. In patients younger than 60 years, vaccination was associated with increased survival.
Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article
Patients and Methods Eighty patients with stage IIIB/IV NSCLC after finishing first-line chemotherapy were randomly assigned to receive best supportive care or EGF vaccinations.
Results Vaccination was safe. Adverse events were observed in less than 25% of cases and were grade 1 or 2 according to National Cancer Institute Common Toxicity Criteria. Good anti-EGF antibody response (GAR) was obtained in 51.3% of vaccinated patients and in none of the control group. Serum EGF concentration showed a major decrease in 64.3% of vaccinated patients. GAR patients survived significantly more than those with poor antibody response (PAR). Also, patients whose serum EGF dropped below 168 pg/mL survived significantly more than the rest. There was a trend to an increased survival for vaccinated patients compared with controls. The survival advantage for vaccinated patients compared with controls was statistically significant in the subgroup of patients with age younger than 60 years.
Conclusion Vaccination with EGF was safe and provoked an increase in anti-EGF antibody titers and a decrease in serum EGF. There was a direct correlation between antibody response and survival. There was a direct correlation between decrease in serum EGF and survival. In patients younger than 60 years, vaccination was associated with increased survival.
Terms in blue are defined in the glossary, found at the end of this article and online at www.jco.org.
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article
Prognostic indices for brain metastases – usefulness and challenges
David Muñoz Carmona
Abstract
Background: This review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG) developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA) classes, i.e. between 1997 and 2008. In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed.
Methods: Based on a systematic literature search, studies with more than 20 patients were included. The methods and results of prognostic factor analyses were extracted and compared. The authors discuss why current data suggest a need for a more refined index than RPA.
Results: So far, none of the indices has been derived from analyses of all potential prognostic factors. The 3 most recently published indices, including the RTOG's graded prognostic assessment (GPA), all expanded from the primary 3-tiered RPA system to a 4-tiered system. The authors' own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool.
Conclusion: This review provides a basis for further refinement of the current prognostic indices
by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types. Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses.
Abstract
Background: This review addresses the strengths and weaknesses of 6 different prognostic indices, published since the Radiation Therapy Oncology Group (RTOG) developed and validated the widely used 3-tiered prognostic index known as recursive partitioning analysis (RPA) classes, i.e. between 1997 and 2008. In addition, other analyses of prognostic factors in groups of patients, which typically are underrepresented in large trials or databases, published in the same time period are reviewed.
Methods: Based on a systematic literature search, studies with more than 20 patients were included. The methods and results of prognostic factor analyses were extracted and compared. The authors discuss why current data suggest a need for a more refined index than RPA.
Results: So far, none of the indices has been derived from analyses of all potential prognostic factors. The 3 most recently published indices, including the RTOG's graded prognostic assessment (GPA), all expanded from the primary 3-tiered RPA system to a 4-tiered system. The authors' own data confirm the results of the RTOG GPA analysis and support further evaluation of this tool.
Conclusion: This review provides a basis for further refinement of the current prognostic indices
by identifying open questions regarding, e.g., performance of the ideal index, evaluation of new candidate parameters, and separate analyses for different cancer types. Unusual primary tumors and their potential differences in biology or unique treatment approaches are not well represented in large pooled analyses.
sábado, 16 de mayo de 2009
Drug may increase survival in brain cancer patients
David Muñoz Carmona
Abstract #2017, Saturday, May 30, 2009. 8 a.m. to 1 p.m.Michael Gruber, M.D., clinical professor of neurology and neurosurgeryShahzad Raza, M.D., clinical research associate in the department of radiation oncologyAshwatha Narayana, M.D., associate professor of radiation oncology
Bevacizumab is a cancer treatment approved by the FDA to treat advanced or metastatic colorectal, lung, and breast cancers, and relapsed malignant glioblastoma, a form of brain cancer. A small study by researchers at NYU Cancer Institute suggests the drug may have a role in treating patients with newly diagnosed glioblastoma. The treatment, which inhibits tumor growth by blocking the formation of new blood vessels, was given to 24 glioblastoma patients who also received radiation and concomitant chemotherapy; another 31 patients received similar treatments but without bevacizumab. The group receiving bevacizumab lived longer during and after treatment without their disease worsening - half of the patients lived without their disease worsening a median of 12 months, compared to seven months in the non-bevacizumab group. One- and two-year overall survival rates were 85 percent and 50 percent, respectively, in the bevacizumab group compared to 74 percent and 22 percent in the other group. The researchers say that the results are encouraging and the drug merits testing in a phase III study.
Abstract #2017, Saturday, May 30, 2009. 8 a.m. to 1 p.m.Michael Gruber, M.D., clinical professor of neurology and neurosurgeryShahzad Raza, M.D., clinical research associate in the department of radiation oncologyAshwatha Narayana, M.D., associate professor of radiation oncology
Bevacizumab is a cancer treatment approved by the FDA to treat advanced or metastatic colorectal, lung, and breast cancers, and relapsed malignant glioblastoma, a form of brain cancer. A small study by researchers at NYU Cancer Institute suggests the drug may have a role in treating patients with newly diagnosed glioblastoma. The treatment, which inhibits tumor growth by blocking the formation of new blood vessels, was given to 24 glioblastoma patients who also received radiation and concomitant chemotherapy; another 31 patients received similar treatments but without bevacizumab. The group receiving bevacizumab lived longer during and after treatment without their disease worsening - half of the patients lived without their disease worsening a median of 12 months, compared to seven months in the non-bevacizumab group. One- and two-year overall survival rates were 85 percent and 50 percent, respectively, in the bevacizumab group compared to 74 percent and 22 percent in the other group. The researchers say that the results are encouraging and the drug merits testing in a phase III study.
High-dose Radiation Improves Lung Cancer Survival, Study Finds
David Muñoz Carmona
Higher doses of radiation combined with chemotherapy improve survival in patients with stage III lung cancer, according to a new study by researchers at the University of Michigan Comprehensive Cancer Center.
Standard treatment for this stage of lung cancer – when the tumor is likely too large to be removed through surgery – involves a combination of radiation therapy with chemotherapy. But, this new study finds, giving chemotherapy at the same time as the radiation enhances the effect of both. Further, increasing the dose of radiation over the course of treatment also increased survival.
“When patients are diagnosed with stage III lung cancer, surgery is often not an option, and survival rates are typically quite low. Finding new ways to improve survival, even in small increments, is crucial,” says senior study author Feng-Ming Kong, M.D., Ph.D., associate professor of radiation oncology at the U-M Medical School and chief of radiation oncology at the VA Ann Arbor Healthcare System.
The study looked at 237 patients who had been treated for stage III non-small cell lung cancer at U-M and the VA Ann Arbor.
The researchers compared survival among patients treated with radiation alone, with radiation followed by chemotherapy, and with radiation and chemotherapy given at the same time. Thirty-one of the patients were also enrolled in a study in which the radiation dose was increased throughout the course of the treatment.
Patients treated with radiation alone had the worst overall survival rates, living only an average 7.4 months after diagnosis. Adding chemotherapy increased survival to 14.9 months when it was administered after completing radiation and 15.8 months when administered at the same time as radiation. After five years, 19.4 percent of the patients receiving concurrent chemotherapy were still alive, compared to only 7.5 percent of patients receiving sequential chemotherapy.
“Our study shows chemotherapy helps, and high dose radiation helps. But it’s challenging to administer these treatments at the same time because of the potential toxicity associated with the high dose radiation,” Kong says.
U-M researchers are currently looking at using PET imaging during the course of lung cancer treatment to personalize high dose radiation therapy in many individual patients. As the tumor becomes smaller during treatment, increasing the radiation dose will become more tolerable because it is targeting a smaller area. The U-M researchers believe this strategy could lead to improved treatment outcomes in many patients. Kong currently leads a clinical trial that is following patients through their treatment to look at the impact on survival of increasing radiation dose.
Lung cancer statistics: 215,000 Americans will be diagnosed with lung cancer this year and 161,800 will die from the disease, according to the American Cancer Society
Additional authors: Li Wang, M.D., Ph.D.; Candace R. Correa, M.D.; Lujun Zhao, M.D., Ph.D.; James Hayman, M.D.; Gregory P. Kalemkerian, M.D.; Susan Lyons, M.D., Ph.D.; Kemp Cease, M.D.; and Dean Brenner, M.D.
Funding was provided through the Pardee Foundation and an American Society of Clinical Oncology Career Development Award.
Reference: International Journal of Radiation Oncology*Biology*Physics, Vol. 73, No. 5, pp. 1383-1390
Higher doses of radiation combined with chemotherapy improve survival in patients with stage III lung cancer, according to a new study by researchers at the University of Michigan Comprehensive Cancer Center.
Standard treatment for this stage of lung cancer – when the tumor is likely too large to be removed through surgery – involves a combination of radiation therapy with chemotherapy. But, this new study finds, giving chemotherapy at the same time as the radiation enhances the effect of both. Further, increasing the dose of radiation over the course of treatment also increased survival.
“When patients are diagnosed with stage III lung cancer, surgery is often not an option, and survival rates are typically quite low. Finding new ways to improve survival, even in small increments, is crucial,” says senior study author Feng-Ming Kong, M.D., Ph.D., associate professor of radiation oncology at the U-M Medical School and chief of radiation oncology at the VA Ann Arbor Healthcare System.
The study looked at 237 patients who had been treated for stage III non-small cell lung cancer at U-M and the VA Ann Arbor.
The researchers compared survival among patients treated with radiation alone, with radiation followed by chemotherapy, and with radiation and chemotherapy given at the same time. Thirty-one of the patients were also enrolled in a study in which the radiation dose was increased throughout the course of the treatment.
Patients treated with radiation alone had the worst overall survival rates, living only an average 7.4 months after diagnosis. Adding chemotherapy increased survival to 14.9 months when it was administered after completing radiation and 15.8 months when administered at the same time as radiation. After five years, 19.4 percent of the patients receiving concurrent chemotherapy were still alive, compared to only 7.5 percent of patients receiving sequential chemotherapy.
“Our study shows chemotherapy helps, and high dose radiation helps. But it’s challenging to administer these treatments at the same time because of the potential toxicity associated with the high dose radiation,” Kong says.
U-M researchers are currently looking at using PET imaging during the course of lung cancer treatment to personalize high dose radiation therapy in many individual patients. As the tumor becomes smaller during treatment, increasing the radiation dose will become more tolerable because it is targeting a smaller area. The U-M researchers believe this strategy could lead to improved treatment outcomes in many patients. Kong currently leads a clinical trial that is following patients through their treatment to look at the impact on survival of increasing radiation dose.
Lung cancer statistics: 215,000 Americans will be diagnosed with lung cancer this year and 161,800 will die from the disease, according to the American Cancer Society
Additional authors: Li Wang, M.D., Ph.D.; Candace R. Correa, M.D.; Lujun Zhao, M.D., Ph.D.; James Hayman, M.D.; Gregory P. Kalemkerian, M.D.; Susan Lyons, M.D., Ph.D.; Kemp Cease, M.D.; and Dean Brenner, M.D.
Funding was provided through the Pardee Foundation and an American Society of Clinical Oncology Career Development Award.
Reference: International Journal of Radiation Oncology*Biology*Physics, Vol. 73, No. 5, pp. 1383-1390
Oligodendrogliomas: Molecular Biology and Treatment
ABSTRACT
Oligodendroglial tumors continue to receive much attention
because of their relative sensitivity to chemotherapy.
The histological diagnosis of oligodendroglial
tumors is subject to considerable interobserver variation.
The revised 2007 World Health Organization
classification of brain tumors no longer accepts the
diagnosis “mixed anaplastic oligoastrocytoma” if necrosis
is present; these tumors should be considered
glioblastomas (perhaps with oligodendroglial features).
The 1p/19q codeletion that is associated with
sensitivity to chemotherapy is mediated by an unbalanced
translocation of 19p to 1q. Randomized studies
have shown that patients with 1p/19q codeleted tumors
also have a better outcome with radiotherapy.
Histologically more atypical tumors are less likely to
have this 1p/19q codeletion; here, other alterations
usually associated with astrocytic tumors are often
found. Some patients with tumors with classic histological
features but no 1p/19q codeletion still have a
very favorable prognosis.
Currently, the best approach for newly diagnosed
anaplastic oligodendroglial tumors is unclear. Early ad
juvant chemotherapy does not provide a better outcome
than chemotherapy at the time of progression. The
value of combined chemoirradiation with temozolomide
has not been proven in these tumors, and could at least
theoretically be associated with greater neurotoxicity.
Tumors with 1p and 19q loss can also be managed with
early chemotherapy, while deferring radiotherapy तो
the time of further progression. The presently available
second-line chemotherapy results are modest, and better
salvage treatments are necessary. The molecular explanation
for the greater sensitivity of 1p/19q codeleted
tumors is still unclear, and this could, in part, be explained
by more frequent MGMT promoter gene methylation.
The Oncologist 2009;14:155–163
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