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Joint AACR-IASLC conference roundup
Source: (cancerfacts.com)
Monday, January 18, 2010
SEATTLE – Jan. 18, 2010 – Below is a brief summary of three clinical trials for lung cancer that generated considerable interest among researchers attending the Molecular Origins of Lung Cancer joint conference of the American Association for Cancer Research and the International Association for the Study of Lung Cancer, which was held in Coronado, California, Jan. 11-14, 2010.
Targeted drug dosing depends on smoking status
Smokers tolerated higher doses of erlotinib
Erlotinib is used as a second-line therapy
Side effects included rash and diarrhea
CORONADO, Calif. – Lung cancer patients who smoke were better able to tolerate more than twice the dose of a targeted therapy drug than non-smokers a new preliminary study shows.
Led by Dr. Lynsay Waller, a fellow at Wake Forest University, researchers presented their findings for a dosing study of the drug erlotinib (Tarceva®) at the AACR-IASLC joint conference last week.
"Increased doses may lead to better outcomes, so we are trying to determine how high we can go with this agent without having to stop (treatment)," said Lynsay in a prepared statement.
Erlotinib, marketed in the U.S. by Genentech, is one of a new class of targeted therapies that are preferentially taken up by cells with certain genetic abnormalities. In the case of erlotinib, the drug targets cancer cells that over produce epidermal growth factor receptor (EGFR), a protein involved in regulating cell division. Erlotinib has been approved for the treatment of locally advanced or metastatic non-small cell lung cancer that has failed at least one prior chemotherapy regimen. In Nov. 2005, the FDA approved it for use in combination with gemcitabine for treatment of locally advanced, inoperable, or metastatic pancreatic cancer.
Its use, however, has bothersome side effects, which include facial acne-like rash, diarrhea and dehydration. The higher the dose, the more effective the drug is in reducing the tumor, but the higher doses also increase the side effects, causing many people to stop treatment.
Waller and colleagues evaluated 25 patients and put them on a chemotherapy regimen that began with a standard chemotherapy regimen including docetaxel and cisplatin along with a drug (pegfilgrastim) to stimulate growth of certain immune system cells.
The researchers then began administering erlotinib at 150 mg daily for non-smokers and 300 mg daily for smokers. These doses were increased every two weeks until development of moderate (grade 2) toxic side effects, at which time the dose levels were maintained. If severe side effects (grade 3 toxicity) occurred, the doses were cut back by 75 mg a day.
Doses reached as high as 525 mg for smokers compared to 225 mg for non-smokers, but by the end of the study most smokers had a maximum tolerated dose of 300 mg compared with 225 mg for non-smokers.
The most common reasons for discontinuation of therapy was grade 2 rash, grade 2 or grade 3 diarrhea or grade 3 dehydration.
Second round of gefitinib may be promising lung cancer therapy
Gefitinib treatment ineffective as first-line therapy
Limited treatment options are available in this patient group
Disease stabilization is observed in many cases
CORONADO, Calif. – Jan. 12, 2010 – Patients with non-small cell lung cancer in whom treatment with gefitinib is ineffective often have limited options, but results of a new study suggest that treating patients a second time with the same drug could benefit these patients.
"The key may be in tumor heterogeneity. That is, within a tumor, some cells do not over produce epidermal growth factor receptor and those cancer cells will fail to respond," said Dr. In-Jae Oh, assistant professor in Chonnam National University Hwasun Hospital in the Republic of Korea, "but we can continue to target the other cells that have become addicted to epidermal growth factor receptor."
For the current study, presented at the AACR-IASLC Joint Conference on Molecular Origins in Lung Cancer, Oh and colleagues evaluated 15 patients with advanced or metastatic non-small cell lung cancer who were retreated with gefitinib after more than one cycle of chemotherapy for advanced or metastatic non-small cell lung cancer.
Among the six patients who had shown a partial response with initial gefitinib treatment, two patients showed an additional partial response and three patients continued to show stable disease.
Among the nine patients who had their cancer stop growing (stable disease) with the initial gefitinib treatment, two patients showed partial response (shrinking tumors) and three patients showed stable disease. The overall disease control rate was 66.7 percent.
"After failure with gefitinib and subsequent chemotherapy, we can try gefitinib again especially for the patients who had previously responded to gefitinib. This strategy will keep some patients from the toxicities of chemotherapy and help maintain the quality of life for several months," said Oh.
Gene IDs lung cancer patients who benefit from drug
Gene rearrangements occur in about 3 to 5 percent of cases
Lung cancer is recognized as different diseases at a molecular level
Results may speed ALK-inhibitor approval in ALK-positive lung cancer
CORONADO, Calif. – Results of a new study in non-small cell lung cancer showed that patients with specific mutations of a gene linked to lymphoma had a much greater response to a new targeted therapy.
Led by Dr. D. Ross Camidge, clinical director of the Thoracic Oncology Program at the University of Colorado, the researchers showed that people with non-small cell lung cancer whose tumors had changes within the anaplastic lymphoma kinase (ALK) gene, had a dramatic response to an investigational new targeted therapy drug. Their findings were presented at the AACR-IASLC Joint Conference on Molecular Origins of Lung Cancer, held last week.
Camidge said this study and its results are an example of how all lung cancers are not created equal.
"This helps prove the principle that there may be many different molecularly defined diseases lurking under the same non-small cell lung cancer umbrella, each of which may derive considerable benefit from drugs that are highly specific to these molecular abnormalities if only we knew what they were," Camidge said in a prepared statement. "Here we have begun to move away from a one-size-fits-all treatment by testing lung cancers for specific genetic changes in advance of choosing the treatment for them."
He adds that this study represents a paradigm shift in cancer drug development as scientists now start to test their molecular hypotheses about which patients a targeted drug may or may not work on from the very first time the drug is tried out in humans.
"If your hypothesis is right, the results can be dramatic and you could shave three to five years off the time from discovery to FDA approval by really focusing on who will benefit the most," he said. "This potentially means getting the right drug to the right patients far quicker than the oncology community has done previously."
Camidge and colleagues have been testing a drug since 2006 called PF-02341066, a small molecule synthesized as an inhibitor of both ALK and cMET, another gene linked to cancer development, in an investigational study involving a small number of patients. The initial findings for this targeted drug were presented at the American Society of Clinical Oncology (ASCO) Annual Meeting, last June.
Study results presented at ASCO explored the initial determination of the appropriate dose of PF-02341066 in patients with all different types of cancers, followed by additional testing of the drug within the same study only in cancers proven to express biological markers of either ALK or cMET activation. In 2007, ALK gene rearrangements, which had previously been reported only in rare lymphomas, were reported in lung cancer and the study was amended to adapt to this emerging data.
Thus far, 31 ALK-positive lung cancer patients have been enrolled in the study. These patients were heavily treated; 65 percent received more than two prior treatment regimens. Patients with the ALK rearrangement had a 65 percent overall response rate, meaning the tumors either stopped growing or began shrinking. There were 19 patients who had a partial response, showing the tumor stopped growing for at least 4 weeks and one patient who had a complete response, with no detectable tumor following treatment.
Patients remained on therapy for a median of 24 weeks, with many still taking the drug.
Adverse side effects associated with PF-02341066 at the study dose have been mild and include stomach and intestinal upsets and dark-light vision disturbances.
For more information on this trial, click on the link for Clinical Trials.gov link for trial number NCT00932451.
SOURCE: adapted from press releases published by the American Association for Cancer Research
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