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Biotech / Medical : IDPH--Positive preliminary results for pivotal trial of ID -- Ignore unavailable to you. Want to Upgrade?

To: scaram(o)uche who wrote (1543)	4/19/1998 10:24:00 PM
From: Maurice Winn	Read Replies (1) \| Respond to of 1762

Okay, so we can use CHOP to really give the NHLs a fright. Then some Oncolym to sort out the men from the boys. Meanwhile some TNT and antiangiogenesis to wreck tumors from the inside out. Then, [there not being enough somatic variations left to form a quorum] the remnants could be dentritic-celled into complete submission. With that onslaught, I wouldn't fancy my chances if I was an NHL cell cowering in some lyph node tucked away in a toenail... That doesn't include a bit of Rituxan or Bexxar which would perhaps be called up as reinforcements after the initial CHOP. I'd have thought that combination attachments to CD20 and the hooks which Oncolym and Bexxar use would be the way to really make a mess of NHLs. The pursuit via somatic variant matching seems less difficult with the advent of Affymetrix type equipment. In the end, using our own immune systems seems the most cunning approach. [or course better still would be genetic selection for no cancer in the first place but that isn't much help to those of us stuck with the pathetic little gene pool donated by our randomly mated parents]. Just some thoughts as a layman. Thanks for the reference and expert comment. Maurice

To: scaram(o)uche who wrote (1543)	5/5/1998 8:05:00 PM
From: Maurice Winn	Respond to of 1762

Rick and all, I hope the Rituxan researchers are correlating Rituxan responses with p53 mutations [refer Nov "Blood"] so that they find some way to discriminate between those who might benefit from Rituxan and those who won't. Better to do that than think that Rituxan doesn't achieve much. Which poor overall results might lead them to think, even though within those results there might be particular people who get great results - if only they could be identified beforehand. Old descriptors such as "follicular", "low grade" etc are useless as correlations. Meanwhile, excitement in the antiangiogenesis field, with IDEC competitor Techniclone market capitalisation jumping. Not such a bargain for IDEC to buy another NHL opportunity now. Maybe still very cheap though. Maurice From Affymetrix thread: -------------------------------------------------------------------- To: jabbo (680 ) From: JF Quinnelly Monday, May 4 1998 11:59PM ET Reply # of 681 MITMay/June '98 Technology Review, Stephen Hall writes: "SCIENCE WRITERS HAVE EXPENDED A GREAT MANY words on "gene chips," which are being touted as biological crystal balls that will diagnose future genetic susceptibility to disease. Having contributed my share of adjectives to this futuristic vision, I know how tempting it is to describe. But technologies often travel the low road to widespread use, and while prognostic gene chips may well be a routine feature of annual physical checkups in the future, a related chip application has already entered the clinic through the back door. "Molecular profiling" is one name this technology goes by, and these highly precise genetic tests do not exactly predict the future. Rather, these chips assess the molecular stage of a patient's disease, and may ultimately suggest which drugs the patient might respond to... ...Given its importance, clinicians would like to know the p53 status of every tumor they're trying to treat. About two years ago, biochip-maker Affymetrix joined forces with Oncormed, a cancer diagnostics company based in Gaithersburg, Md., to make p53 testing one of the prototypes of chip technology. Their target: the coding region of the human p53 gene, which possesses 1,262 base pairs of DNA-the chemical subunits of the double helix that tell a cell how to make the p53 protein. Affymetrix, based in Santa Clara, Calif., has created a p53 chip that measures slightly less than 13 millimeters square~bigger than a thumbtack, but smaller than the standard issue 32-cent stamp. Engineers at Afymetrix have subdivided this real estate into a checkerboard of 20,000 "probe cells;' each bristling with a uniform carpet of millions of identical DNA probes measuring 18 base pairs long. Using fluorescently labeled reagents, prepared DNA from a tumor can be washed over the chip, and extremely sensitive scanners are programmed to detect minuscule variations in intensity in the checkerboard pattern-which arise from slight genetic changes in p53. Once the DNA has been prepared, the test can be done in four hours. Although p53 is only one of numerous genes implicated in the evolution of a tumor, it has already been thrust into a prominent role in experimental cancer treatments. In April of 1996, for example, Oncormed began using the Affymetrix chip to perform "molecular staging"-that is, assessing the status of a tumor-in patients with head and neck cancers prior to clinical testing of an experimental form ofgene therapy developed by Onyx Pharmaceuticals. The therapy is in Phase II testing, and some patients have responded favorably in preliminary results. The ability to do molecular profiling, according to Leslie Alexandre, a vice president at Oncormed, allows oncologists to determine both the virulence of a tumor and the extent of its metastatic spread. "If there is a p53 mutation in the tumor," she says, "then you would look at the lymph nodes and look for the fingerprint to see how far the tumor has spread." Oncormed has reached agreements with RhonePoulenc Rorer and Schering-Plough to do p53 testing associated with gene therapy trials. The potential significance of such testing goes well beyond staging individual tumors. Drug companies are intensely interested in ways of predicting which patients are likely to respond to chemotherapy, and there is some evidence that p53-and molecular profiling like it-may help identify patients likelier to respond. Not only will this allow drug companies to achieve higher response rates in drugs being tested, but it may, Alexandre says, provide a way to "resurrect" drugs that fail in Phase III trials by identifying a small group for whom the drug is very effective..."

To: scaram(o)uche who wrote (1543)	3/15/1999 12:56:00 AM
From: Bob L	Respond to of 1762

Richard, here is another piece of the article we were discussing on the cltr thread. Czuczman et al in Treatment of Patients with Low-Grade B-Cell Lymphoma with the Combination of Chimeric anti-CD20 Mab and CHOP Chemotherapy, Journal of Clinical Oncology Vol.17,No.1(Jan) 1999 pp268-276. Mention of chemo at end. I'll see what I can do with the tables in a separate post. Response to Therapy Median time to response was 47 days (range, 15 to 236 days). The overall response rate to the combination of CHOP and Rituxan treatment was 95% (95% confidence interval, 88% to 100%) in the intent-to-treat patient population (Table 3). Twenty-two patients (55%) experienced a CR, and 16 patients (40%) had a PR. Thus, only the two patients who were withdrawn from the study before the initiation of trial therapy were classified as nonresponders (one with an IWF histologic classification of A and the other, B). Response rates were also evaluated for patient subpopulations, including those with extranodal disease, an elevated serum lactate dehydrogenase concentration, bone marrow involvement, an age of 60 years or more, or bulky disease (Table 3). Combination Rituxan and CHOP therapy achieved at least a partial response in all of the patients, and the complete response rate was less than 45% only for those patients with bulky disease. Twenty-eight (74%) of 38 assessable patients continued in remission after a median observation time of 29 months (Fig 2). There were 24 assessable (plus one unassessable) newly diagnosed patients with follicular histology, and they all responded to therapy (16 CR and eight PR). The median duration of response was yet to be reached at 27.8+ months. There was no significant difference in duration of response between naive and previously treated patients. There were nine patients with IWF type A histology. Of these, one patient was unassessable, and the other eight patients were responders (three CR and five PR). The median duration of response for the IWF type A patients had not been yet reached at 17+ months. Five of the eight patients were in ongoing remissions. At that time, there was no significant difference in rate or duration of response when these patients were compared with the rest of the study patients. Eight of the nine patients who had received chemotherapy treatments before study entry responded to therapy with Rituxan and CHOP (Table 4). Five of these responses were complete; two of the complete responses occurred in patients who had experienced either progressive disease or a partial response with their last prior chemotherapy regimen (cyclophosphamide, vincristine, prednisone and chlorambucil, prednisone, respectively). [End of Response to Therapy section]