Clinical trials are always bumpy roads. While the announcement from Dr. Kaelin is disappointing, we should point out that Novartis is being very responsible with this drug. This is not the only drug awaiting trial. There are alternative drugs "in the pipeline" that we expect to pick up where this one left off, but it will slow down the process a bit.

The patients taking PTK are doing fine. The snag came in Novartis' long-term testing on dogs. Not every drug is put through long-term testing this early, so it is very much to our benefit that this long-term testing be done. A few of the animals developed complications after long-term use. They are now evaluating which of the related drugs also in preparation might have the same positive effects without the negative side-effects.

Please remember that this is not the only drug, that there is still plenty of hope on the horizon, it's just always a bumpy road. This is what drug testing is all about -- better we should find out the downside now among other animals rather than find out 10 or 20 years from now when someone we thought was doing well winds up with some unwelcome side effect.

The data from Phase 1 trials of this and similar drugs are relatively reassuring, with only a few mild side-effects from the current treatments, and no hemorrhages (always the biggest fear). Because of this, there is hope that we can get permission to involve people with VHL at earlier stages in the testing of subsequent drugs. This may mean that there will not be very long delays for the people in the "compassionate exemption" category who were anxiously awaiting the start of this trial because their condition is imminently life-threatening.

If you need additional information about the Novartis PTK78 trial, please contact Dr. William Kaelin, Dana Farber Cancer Research Institute, 44 Binney Street, Boston, MA 02115 USA; +1 (617) 632-4747 (Sarah); Fax: +1 (617) 632-4381; E-mail: sarah_alwardt@dfci.harvard.edu

Meanwhile, the Sugen trial continues, and Sugen is open to enrolling additional local physicians to allow local administration of SU5416. Long-term studies have not yet been completed for SU5416 (scheduled for 2000), but SU5416 is now in Phase 3 for other conditions. See article in VHLFF, September 1999 (http://www.vhl.org/newsletter/vhl1999/99cbclin.php). Early feedback from two people with VHL is that there is no perceptible tumor shrinkage, but it’s early yet. Linda W., whose primary problem was pressure on the optic nerve that was steadily reducing her vision, reports that her vision is much improved even though the tumor does not show much if any shrinkage; Geoff M. reports that his symptoms have not been relieved. So there are no clear results at this time.

SU5416 has to be administered intravenously twice a week in 4-week cycles. We do not yet know the consequences of going off any of these drugs. Also, we have noticed that the restrictions in entering trials (e.g. SU5416) may involve excluding people who have been on another anti-angiogenic therapy trial, so people should not rush to judgment in enrolling in a trial. Unless their situation is pretty scary, we would suggest they wait.

Considering a Clinical Trial? Questions to ask before you decide.

Two additional Sugen sites have been added, in France and Poland:

- Dr. Adrian Harris, Med Oncology, Churchill Hospital, Headington, Oxford OX3 7LJ England, U.K. Tel: +44 (0)1865 226184; Fax: +44 (0)1865 226179; E-mail: v.berry@icrf.icnet.uk

- Dr. Karol Krzystolik, Dr. Karol Krzystolik, Dept Genetics, Pomeranian Academy of Medicine, ul. Powstancow Wlkp. 72, Szczecin 70-111 Poland. Tel/Fax: +48 (91) 4828 450; E-mail: poland@vhl.org

- Dr. David Palchak, 1184 Grand Avenue, Arroyo Grande, CA, USA, 93420, Tel: +1 (805) 473-8983; Fax: +1 (805) 473-8735; E-mail: dpalchak@pol.net

- Dr. Stéphane Richard, Oncogenetics, Kremlin-Bicêtre Hospital, 61 rue Gabriel Péri, Le Kremlin Bicetre Cedex F-94276 FRANCE, Tel/Fax: +33 (1) 49 59 67 28; E-mail: stephane.richard@kb.u-psud.fr

- Peter Hirth, Executive VP, Drug Research & Development, 230 East Grand Ave., South San Francisco, CA 94080 USA; Tel: +1 (650) 553-8707; Fax +1 (650) 553-8303; E-mail: peter-hirth@sugen.com

As printed in the VHL Family Forum 7:4, December 1999. For permission to reprint, please contact VHL Family Alliance, editor@vhl.org. Further information is available from the VHL Family Alliance, info@vhl.org.