EGFr inhibitors
Dr. Cancerblogger ( oncologynews.info ) has a little piece on Iressa which I found interesting for a couple of reasons.
January 07, 2004
There are oncologists out there (I know from personal experience) who almost refuse to use geftinib (Iressa) because of the reported low response rate of 10%. They will treat their lung cancer patients with regimen after regimen, wearing them down, and only resort to geftinib when their patients are ready for hospice care. Quality of life seems not to be a factor in the decision-making. This article highlights an important statistic: that the overal disease control rate for geftinib is 53%! This is because in addition to the response rate, there is an additional 43.8% of patients for whom the disease remains stable, and in some cases, this response can last for over a year. Quality of life is very good. One can always go back on chemo later if there is still a reasonable option, so no bridges are burned.
As Dr. Cancerblogger is involved in the daily fight against cancers his opinion on what should be considered a good response is of interest as it gives some perspective, when the results from other companies' cancer trials are reported.
The corresponding abstract:
Ann Oncol. 2004 Jan;15(1):33-7. Related Articles, Links
Activity of a specific inhibitor, gefitinib (Iressa(TM), ZD1839), of epidermal growth factor receptor in refractory non-small-cell lung cancer.
Santoro A, Cavina R, Latteri F, Zucali PA, Ginanni V, Campagnoli E, Ferrari B, Morenghi E, Pedicini V, Roncalli M, Alloisio M, Ravasi G, Soto Parra HJ.
Department of Medical Oncology and Hematology, Istituto Clinico Humanitas, Rozzano, Milan.
BACKGROUND: Gefitinib (Iressa(TM), ZD1839) is an orally active, selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Phase I studies showed that it is well tolerated, with evidence of tumor regression in patients with advanced non-small-cell lung cancer (NSCLC). Therefore, we aimed to assess the antitumor activity and tolerability of gefitinib in a series of patients with previously treated, advanced NSCLC, as a part of a compassionate use program.
PATIENTS AND METHODS: To be eligible, all patients were required to have histologically or cytologically proven advanced or metastatic NSCLC, prior chemotherapy with at least one cisplatin-containing chemotherapy regimen or contraindication to cytotoxic drugs, Eastern Cooperative Oncology Group performance status </=2, and adequate hematological, renal and hepatic parameters. All patients provided signed informed consent. Patient re-evaluation was performed every 4-6 weeks.
RESULTS: Seventy-three consecutive patients were enrolled. Response rate, including complete and partial response, was 9.6%; an additional 43.8% of patients achieved stable disease, for an overall disease control of 53.4%. EGFR1 status was evaluated by immunocytochemistry in 25 patients. According to EGFR1 immunoreactivity all responses were observed with medium/strong imunoreactivity while three out of four responses were observed in high expressive patients. Median survival for all patients was 4 months while it reached 6 months for patients with disease control. The 1-year survival rate was 13.1% for the entire series and 23.2% for patients with disease control. Non-hematological toxicity was generally mild.
CONCLUSION: Gefitinib has promising activity with a good toxicity profile in patients with progressive NSCLC who have received one or two prior chemotherapy regimens. A possible relationship within response and EGFR1 expression is suggested.
PMID: 14679116 [PubMed - in process]
Disease control is btw. a rather odd term. Judging from the reported results not much of a control was achieved. Half of the patients having their cancer "controlled" had anyhow died within 6 months and only 23 % were alive after 12 months. In most cases it seems that the disease was not at all controlled, but maybe its progress was to a certain extent slowed down.
Erik |
