A recombinant blood growth factor, GM-CSF, has improved theodds of giving higher doses of chemotherapy to kill tumor cells,without destroying infection-fighting white blood cells as well.

A clinical trial reported in the August issue of the Journal ofClinical Oncology found that GM-CSF (granulocyte-macrophagecolony-stimulating factor) markedly reduced the ravages ofanti-cancer chemicals on bone-marrow, which producesneutrophils -- white blood cells that mop up invading bacteria.

The major drawback of such drugs -- notably Cytoxan,Adriamycin and dacarbazine -- is that their dosage andfrequency, and hence, their anti-tumor effectiveness, must beheld down, to keep a patient from dying of their major sideeffect, neutropenia. This wipeout of white blood cells brings onlife-threatening infection.

Researchers conducting the study at the University of TexasM.D. Anderson Cancer Center gave end-stage sarcoma patientsescalating doses of GM-CSF supplied by Immunex Corp. andHoechst-Roussel. Immunex expresses the geneticallyengineered protein in yeast cells.

After 23 patients had received 111 rounds of GM-CSF plus theCytoxan-Adriamycin-dacarbazine cocktail, the Houstonclinicians concluded: "Our results demonstrate that GM-CSF,when administered immediately after a compressed scheduleof (combination) chemotherapy, enhanced myelo (bone-marrow) protection ... and allowed dose-intensification ofchemotherapy."

Fortified by these and other recent clinical findings, Immunex,which supplied its GM-CSF for the trial, plans to apply to theFDA "this year to broaden the indication label to coverneutropenia caused by chemotherapy," said the Seattlecompany's vice president for communications, Jason Rubin. Atpresent, Rubin told BioWorld, GM-CSF is approved only "toaccelerate bone-marrow engraftment and to prolong survivalwhen such treatment fails."

Neupogen, the G-CSF (granulocyte colony-stimulating factor)produced by Amgen, already enjoys the chemotherapy-enhancing FDA label.

Wertheim Shroder & Co. analyst Jay B. Silverman cited theJournal of Oncology Study, along with two other trials in hisreiterated recommendation of the stock on Thursday.

Immunex (NASDAQ:IMNX) closed Thursday at $35.75 pershare, up $1.75.

Silverman wrote that a study published in the August issue ofthe Annals of Internal Medicine "bodes extremely well for thepotential of (Immunex's) PIXY321, which may be highlyeffective as a single agent molecule in raising both neutrophilsand platelets, and which also may address markets whereNeupogen has been ineffective."

A study sponsored by Schering-Plough published in the Julyissue of the Journal of American Medicine described very lowdoses of GM-CSF given alone or with erythropoietin to patientswith aplastic anemia. Silverman wrote that this study " willhelp support wider usage of GM-CSF and the likelihood of anexpanded label.

Jordan U. Gutterman, who chairs the department of clinicalimmunology and biological therapy at M.D. Anderson,commented on the trial results, which were initially reported inMay 1991 to the American Society of Clinical Oncology inHouston. "Now that the article has finally been published, it ismy perspective that it will have an influence among practising,as well as research, oncologists." Gutterman added, "All sorts ofother studies are going on -- G-CSF, GM-CSF and IL-3-- tryingthe effect of these blood growth factors administered before aswell as after cycles of chemotherapy. "

-- David N. Leff Science Editor

(c) 1997 American Health Consultants. All rights reserved.

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