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Irinotecan(CPT-11, Comptosar) and E7070????


Henry1929

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My wife has been hoping for a place in a trial with Gemzar and flavopiridol. But if it doesn't open up doc is suggesting a trial with Irinotecan and an experimental, E7070, a sulfonamide (?). Irinotecan (aka CPT-11 or Comptosar) is approved for lung and been around for a while. Can't find much about E7070. Has any one had any experience with either of these?

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I have not heard of E7070. What does your doctor think of tarceva or Canertinib (CI-1033). They are like Iressa. It seemed like there was a response to Iressa - I wonder if Tarceva would work. I am not a doctor. Talked to your doctor. Iressa type drugs are supposed to work the best for non-smoking women. Though I am not sure what the exact response rate actually is.

Of course Erbitux is also like Iressa except a different "formula"

INFO on E7070 below. NOTE this is a trial of E7070 by itself and not with CPT-11. The two may work better together, but the one study below said there was low objective response of using it alone

A phase II and pharmacodynamic study of E7070 in patients with non-small cell lung cancer (NSCLC) who have failed platinum-based chemotherapy

Abstract No: 1306

Author(s): Denis Talbot, Chris Norbury, Mark Slade, Joachim von Pawel, Leon Bosquee, Paul A Ellis, Ulrich Gatzemeier, Miroslav Ravic, ICRF Churchill Hospital and IMM, Oxford, UK; Asklepios Fachkliniken, Munchen-Gauting, Germany; La Citadelle, Liege, Belgium; Guys Hospital, London, UK; KH, Grosshansdorf, Germany; Eisai Ltd, London, UK.

Abstract: Purpose: 1) Determine the clinical activity of E7070 as second line treatment of NSCLC 2) Quantify apoptosis and aneuploidy in tumours from patients (pts) treated with E7070 Method: Pts with advanced NSCLC who had failed platinum-based chemotherapy were r andomised to receive E7070 iv 3 weekly at either 700mg/m2, dx1 or 130mg/m2, dx5. Cell cycle analyses were performed on biopsies and aspirates of soft tissue metastases (BX) or bronchial washings (BW) and brushings (BB) before and 48 hr after E7070. BW, B B and tumour aspirates were fixed in 70% ethanol, stained with propidium iodide and analysed by flow cytometry. Tumour biopsies were disaggregated in PBS/trypsin/collagenase before ethanol fixation. Red fluorescence (DNA) data were collected on 10,000 ce l l s/sample. DNA content was assessed as apoptotic (G1 content). BW&BB from the contralateral, unaffected lung were used as controls. Results: 44 pts were enrolled: 35M/9F, median KPS score 80 (ran ge 7 0-100), median age 59y (35-76y), Stage IIIb 20, IV 24. Response: dx1, PR 1 (6%), SD 7 (47%), PD 7 (47%); dx5, PR 0 SD 3 (23%) PD 10 (77%). Toxicity: neutropenia: 5 (11%) pts, anaemia: 2 (5%) pts, other: asthenia and injection site reaction. 3 pts wer e e ligible for cell cycle analyses (2 BW/BB and 1 BX). All generated sufficient material for analysis. Two pts showed a marked increase in the apoptotic fraction after treatment, with a simultaneous decrease in the proliferating/aneuploid fraction (reduc ti on in the >G1 population from 67% to 17% and 22% to 6%, respectively). Of these, none achieved an objective clinical response. Pharmacokinetic analysis of E7070 is ongoing. Conclusion: BB samples appear to be more sensitive than BW for the detection of pr ol if erating and aneuploid cells from endobronchial NSCLC compared to controls. Core biopsy material from soft tissue metastases are also suitable for flow cytometric analysis. E7070 is a well tolerated agent in previously treated pts but has a low objective response rate as second line therapy in NSCLC, despite the induction of significant tumour cell apoptosis in vivo..

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Thank you John and Sherriot for your replies. Info was helpful. As for Iressa - tarceva , doc suggested she could try tarceva after the iressa failed but his thinking was that her tumor had developed a secondary mutation causing the failure and since tarceva is close to the same it may not work or not work for long. He had an experimental from BMS in mind that is a broader kinase inhibitor and more likely to be a success aginst the new mutation. So we waited to get on trial only to find that BMS would not accept her because of the brain issues. One of the problems with trying to get on trials is the need to have been off treatment for 30 days in many cases, so we have held off trying the tarceva. We are hoping for a place in the Gemzar/flavopirinol trial, the CPT-11 / E7070 sounds kind of rugged in terms of side effects so she may opt for a standard treatment if the trial doesn't work. Very hard to go back to a chemo after 7 months on a pill and then feeling good with no treatment! Our Docs are good, always get back to us, but waiting.....!!

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