arnesyltransferase inhibitor SCH 66336

Looks pretty good so far...

[1068] The combination of paclitaxel and the farnesyltransferase inhibitor SCH 66336 in the treatment of metastatic breast cancer. A phase I/II study.

Rossner D, Hollwitz B, Schaff C, Ay A, Rinnau F, Lersch W, Kühnle H.. Med. University Hannover, Hannover, Germany; Essex Pharma, Munich, Germany

In solid tumors the ras oncogene is an important regulatory unit in the signal transduction pathway. For activation of ras a farbesylation step is necessary. Preclinical studies are able to show a synergistic effect of paclitaxel and the farnesyltransferase inhibitor (FTI) Sch 66336.
In this study up to now 19 patients with multiple treated metastatic breast cancer were treated with paclitaxel 80 mg/m weekly and 125 SCH 66336 bid every day. The combination was given for 12 weeks, followed by a treatment with the FTI alone.
At this time 18 patients are disposal for toxicity, and 14 for efficacy. 6 patients still under treatment.
The median age was 51 y (36 y 80 y). 17 of 19 patients were pretreated with anthracyclines and taxanes. 8 patients were refractory to the last chemotherapy treatment.
Toxicity: haematological toxicity grade III (Leukopenie) was observed in 5 of 19 patients. No patients with severe anaemia or thrombopenia were recognized. Non-hematologic toxicity: diarrhoea grade III/IV was observed in 3 of 18 patients. In all cases the symptoms stops after reduction of SCH 66336 to 100 mg bid. Paclitaxel associated toxicities like PNP, myalgia and athralgia were observed, but no grade III toxicities.
Efficacy: One patient is more than 12 moths in a CR. 5 patients with a PR and 2 with a minimal response were observed. There was no patient with a primary treatment failure.
Conclusion: SCH 66336 are able to stop tumor growth alone and in combination with paclitaxel. The numbers of side effects are acceptable, but the daily dose of SCH 66336 should not be higher than 100 mg bid per day. The observed efficacy is promising and should be evaluated in further studies.


Wednesday, December 8, 2004 4:30 PM