I think that Iressa is doing worse in real world than trials data indicate. Small numbers of Rx and very few pts stay on therapy longer, I guess side effects problems and death.
Even today JCO article on glioblastoma PII do not suggest great success, as ML guy pumped last year.
Press Release Source: AstraZeneca
Phase II Trial Data for IRESSA(R) (gefitinib) in Recurrent Brain Cancer
Thursday January 8, 9:25 am ET
New Results Published in the Journal of Clinical Oncology
WILMINGTON, Del., Jan. 8 /PRNewswire-FirstCall/ -- New data published this week in the Journal of Clinical Oncology (JCO) highlight the first Phase II clinical trial of IRESSA® (gefitinib) Tablets in patients with recurrent glioblastoma. Glioblastoma is the most common of the primary malignant brain tumors and is one of the most challenging to treat effectively, with a 5-year survival rate of approximately 5 percent.
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"We continue to look for better treatments for those diagnosed with this lethal cancer," said Judith Ochs, MD, Senior Medical Director of Clinical Research for IRESSA at AstraZeneca.
The open-label, single-center Phase II trial included 57 patients with first recurrence of a glioblastoma who were previously treated with surgical resection, radiation, and usually chemotherapy. These patients underwent an open biopsy or resection at evaluation for confirmation of tumor recurrence. Each patient received 500 mg of IRESSA orally, once daily. Dose escalation to 750 mg and 1000 mg occurred if a patient received enzyme-inducing antiepileptic drugs or dexamethasone.
The primary endpoint of the study was 6-month progression-free survival, with secondary endpoint measurements of tumor response rate, event-free survival, overall survival, and drug toxicity. No patient had either complete response or partial response, and 31 patients had radiographic progressive disease (58.4%) within the first two months. In total, 51 of the 53 assessable patients eventually developed progressive disease, with two patients remaining on therapy at the time of manuscript preparation; 21 percent of patients (11 of 53) had measurable disease at treatment initiation. Seventeen percent of patients (nine of 53) underwent at least six 4-week cycles of IRESSA. The 6-month event-free survival was 13 percent (seven of 53) and the median duration of event-free survival was 8.1 weeks. The median overall survival time from treatment initiation was 39.4 weeks.
Adverse events were generally mild to moderate (grade 1 or 2) and consisted mainly of skin reactions (60%) and diarrhea (40%). Other toxicities that were encountered that were felt to be possibly related to the use of IRESSA included conjunctivitis, onycholysis, anorexia, weight loss, and AST and ALT elevation. Drug-related toxicities were more frequent at higher doses. Patient withdrawal caused by drug-related adverse events occurred in 6 percent (three of 53) of patients receiving 500-1000 mg/day of IRESSA.
Glioblastoma represents approximately 20 percent of all primary tumors found in the brain. Each year approximately 5 of every 100,000 individuals in the United States are diagnosed with glioblastoma. The disease is typically found in people 40 to 60 years of age and occurs slightly more often in males than in females. Glioblastoma is considered an aggressive tumor; it usually recurs within 1-2 cm of the original tumor site. While it may spread to surrounding tissue within the brain, it rarely spreads to other parts of the body. Due to its location in the brain, however, it is usually rapidly fatal. |
