Gefitinib-induced cell death in short term fresh tumor cultures predicts for long term patient survival in previously-treated non-small cell lung cancer.

Sub-category:

Non-Small Cell Lung Cancer

Category:

Lung Cancer

Meeting:

2006 ASCO Annual Meeting


Abstract No:

17117

Citation:

Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 17117

Author(s):

L. Weisenthal

Abstract:

Background: Gefitinib (GEF) may act by inhibiting anti-apoptotic signals transduced by mutant EGFR kinase (Science 305:1163,04). Cell culture assays with cell death endpoints could be informative for GEF activity. Methods: We tested 568 biopsies of fresh human tumors (TUM) with 2 concentrations of GEF (22 and 11 µg/ml) for 96 hrs, each with 2 separate cell death endpoints (DISC and MTT), detailed methods http://weisenthal.org/w_ovarian_cp.pdf. Results classified as resistant (RES), intermediate (INT), or sensitive (SEN) based on means and standard deviations of training set data (ref ibid), reported prospectively to 3 different physicians: surgeon, pathologist, and oncologist. Assay evaluability rate > 90%. Results: Based on overall % control cell death, the following TUM showed (on average) no greater RES or SEN than the universe of 568 assays: NSCLC (n = 72), colon (33), breast (106), ovarian (109), melanoma (23), pancreatic (20), endometrial (12). The following showed (on avg) significantly greater RES: soft tissue sarcomas (n = 24), carcinoid/islet (16), renal (15), and mesothelioma (8). For NSCLC, there was no avg difference between female (32) vs male (35) or untreated (34) vs previously treated (38). For 32 unRxd pts with survival data, there was no significant difference in overall surv for 20 pts with prospectively reported GEF RES (GR) assays vs 12 pts with SEN or INT (GSI) assays. For 31 pts with prior chemoRx (med surv = 155 days), there was significant survival disadvantage for 14 pts with prospectively reported GR vs 17 pts with GSI (median 85 vs 380 days, P2 < 0.0001, HR 3.7; 95% C.I. 2.6-19) (Click here to see Kaplan-Meier Curves). For pts with known post-assay Rx, there were 7 pts with GSI subsequently receiving GEF or erlotinib (ERLOT), with med surv = 485 days; 9 pts with GSI not receiving GEF or ERLOT, med surv = 135 days; 10 pts with GR not receiving GEF or ERLOT, med surv = 76 days, and 3 pts with GR receiving GEF or ERLOT, med surv = 75 days. Survival of group of 7 pts was significantly greater than those of groups of 9, 10, and 3 pts (P2 = 0.037, P2 < 0.0001, and P2 = 0.0008, respectively, click here to see Kaplan-Meier Curves). Conclusions: GEF-induced cell death in cultures of fresh TUM from prev-treated NSCLC pts may identify pts with favorable prognosis, particularly when treated with GEF or ERLOT.

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Abstracts by L. Weisenthal

 

1.

Gefitinib-induced cell death in short term fresh tumor cultures predicts for long term patient survival in previously-treated non-small cell lung cancer.

Meeting: 2006 ASCO Annual Meeting   Abstract No: 17117   First Author: L. Weisenthal
Category: Lung Cancer - Non-Small Cell Lung Cancer

 

2.

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