Gefitinib for advanced lung cancer trial closes early
Researchers have closed a randomized clinical trial comparing gefitinib (Iressa) vs. placebo following chemotherapy and radiation for patients with non-small cell lung cancer (NSCLC) that had spread only to nearby tissues or lymph nodes. Review of interim data indicated that gefitinib would not improve survival.
Based on a review of the limited data available from the Phase III clinical trial, the Data Monitoring Committee overseeing the trial recommended the closure. Detailed results from the study were presented at the American Society of Clinical Oncology Annual Meeting on May 14.
The study was designed to assess whether maintenance therapy with gefitinib would improve overall survival and progression-free survival as compared to placebo in patients with stable or responding disease. These patients had inoperable stage III NSCLC and already had completed the combined chemotherapy regimen of cisplatin and etoposide with radiation, followed by docetaxel. A total of 672 patients in this study were to be randomized to one of two treatment arms following chemotherapy and radiation: One arm would receive gefitinib daily and the other arm would receive a placebo daily. As of March 10, 611 patients were entered and 276 were randomized to one of the two arms.
The National Cancer Institute sponsored the trial.
Survey: Patients struggle with drug compliance
One in three (33%) U.S. adults who have been prescribed drugs to take on a regular basis reported that he or she is often or very often noncompliant with the treatment regimen, according to a recent Harris Interactive on-line survey. In addition, nearly half (45%) of the respondents said they have failed to take their medications because of concerns they had about the drugs themselves, and 43% reported having not complied with their regimens because they felt the drug was unnecessary.
The survey of 2,507 U.S. adults was conducted between March 16 and 18 for The Wall Street Journal Online’s Health Industry Edition.
Of the 63% of adults who have had prescription drugs prescribed to them in the last year — drugs that should be taken regularly — nearly two-thirds (64%) reported that they have simply forgotten to take their medication. Eleven percent said this has happened "often" or "very often." Other top reasons respondents cited for noncompliance with their treatment regimens include:
- I had no symptoms or the symptoms went away (36%).
- I wanted to save money (35%).
- I didn’t believe the drugs were effective (33%).
- I didn’t think I needed to take them (31%).
- I had painful or frightening side effects (28%).
- The drugs prevented me from doing other things I wanted to do (25%).
"These barriers leading to noncompliance present significant challenges to physicians and the U.S. health care system as a whole that will be difficult to address," says Katherine Binns, senior vice president of healthcare research at Harris Interactive.
Bevacizumab with chemotherapy improves breast cancer survival
Preliminary results from a large, randomized clinical trial for patients with previously untreated recurrent or metastatic breast cancer show that those patients who received bevacizumab (Avastin) in combination with standard chemotherapy had a longer time period before their cancer progressed than patients who received the same chemotherapy without bevacizumab.
Preliminary results suggest that patients in the study who received bevacizumab in combination with standard chemotherapy consisting of single-agent paclitaxel had a delay in worsening of their cancer by four months, on average, compared to patients treated with paclitaxel chemotherapy alone. This difference is statistically significant.
A total of 722 women with recurrent or metastatic breast cancer who had not previously received systemic chemotherapy for their recurrent or metastatic disease were enrolled in this study between December 2001 and May 2004. Patients were randomized to one of the two treatment arms. One patient group received standard treatment consisting of single-agent paclitaxel. The second group received the same regimen of paclitaxel with the addition of bevacizumab.
The National Cancer Institute sponsored this trial.
PharMEDium Services recalls all lots and strengths of IV solution
PharMEDium Services of Houston is recalling all strengths of 50 mL admixtures of magnesium sulfate in 5% dextrose solution because of a potential lack of sterility assurance for these products. In addition, the company is voluntarily ceasing production and distribution of the product until it can determine and correct the source of this problem.
Two previously distributed lots of this product have been associated with outbreaks of Serratia marcescens infection, which can potentially cause serious or life-threatening conditions in patients (particularly among the immune-compromised).
The products subject to recall are those labeled under the following service codes:
These products were manufactured by PharMEDium Services of Houston and were distributed to several hospitals around the country.
On March 18, the FDA issued a nationwide alert regarding PharMEDium Services Magnesium Sulfate 1 g in 50 mL D5W (piggyback) IV solution, lot number 100504900049 and expiration date 4/4/05, after it was associated with five cases of S. marcescens infection in a hospital in New Jersey.
The company is working with the FDA, the U.S. Centers for Disease Control and Prevention, and other public health authorities. Hospitals with questions may contact the company at (847) 457-2300.
Enrollment stopped in drotrecogin alfa (activated) pediatric trial
Eli Lilly and the FDA have notified health care professionals that enrollment has been stopped in a randomized, double-blind, placebo-controlled trial of drotrecogin alfa (activated) (Xigris) in pediatric patients with severe sepsis. Drotrecogin alfa (activated) is not indicated for use in pediatric severe sepsis.
A planned interim analysis showed that drotrecogin alfa (activated) was highly unlikely to show an improvement over placebo in the primary endpoint of "Composite Time to Complete Organ Failure Resolution" over 14 days.
A numerical increase in the rate of central nervous system bleeding in the drotrecogin alfa (activated) vs. the placebo group was also noted. Over the infusion period the number of patients experiencing an intracranial hemorrhage event was four vs. one for the overall population (drotrecogin alfa (activated) vs. placebo), with three of the four events in the drotrecogin alfa (activated) group occurring in patients age 60 days or younger. Mortality, the rate of serious adverse events, overall serious bleeding events, and major amputations appeared to be similar in the drotrecogin alfa (activated) and placebo groups.
For the complete MedWatch 2005 Safety summary, see www.fda.gov/medwatch/SAFETY/2005/safety05.htm#biologics.
FDA updates albumin administration advice
The FDA issued a notice on May 16 to update an earlier correspondence and to revise its previous advice about the safety of albumin administration in critically ill patients. The action was taken following the FDA’s review of recent studies on the safety of albumin; it also is consistent with recommendations made on March 17 by members of the Blood Products Advisory Committee (BPAC).
In an Aug. 19, 1998, letter to health care providers, the FDA had expressed serious concern over the safety of albumin administration in critically ill patients and urged physicians to exercise discretion in its use.
This advice was based on a meta-analysis published in the July 25, 1998, issue of the British Medical Journal. The researchers found that compared to normal saline, albumin administration was associated with a 6% increased risk of dying; similar findings were noted for patients with hypovolemia, hypoproteinemia, and burns.
Then the New England Journal of Medicine published the SAFE study in its May 27, 2004, issue. SAFE is the largest randomized controlled trial to date to address the safety of albumin. In this trial, 6,997 critically ill subjects were randomized to receive either 4% albumin or normal saline for the treatment of hypovolemia.
The results presented by the principal investigator at the BPAC meeting on March 17, 2005, indicate that for patients in the general intensive care unit requiring fluid resuscitation, the mortality rate of those who receive albumin is the same as for those who receive saline.
Secondary analyses of pre-specified subgroups of patients with acute respiratory distress syndrome (ARDS), severe sepsis, and trauma were consistent overall with this finding.
Two additional findings deserve mention, according to the FDA. First, results of an exploratory analysis of trauma patients with concomitant traumatic brain injury showed increased mortality in the albumin treatment arm. Second, a higher survival rate was observed in the albumin-treated patients with severe sepsis, but since this finding was not statistically significant, its clinical significance remains uncertain.
Based on these data, the BPAC voted unanimously that the SAFE study had resolved the prior safety concerns raised by the 1998 researchers. However, the relative safety of albumin for use in patients with burns cannot be determined at this time as this group was excluded from the SAFE study.
Additionally, further evaluation of albumin in patients with traumatic brain injury and septic shock will have to be performed to determine the safety of albumin administration in these patient populations.