Chemosensitivity of patient derived human tumor xenograft models against 5FU, Capecitabin, CPT-11 and Oxaliplatin

2219 Patient derived tumor models established sc in nude mice have been shown to predict well the response of standard and novel agents compared with clinic activity. In 80 comparisons we have treated the same tumor in the patient and in the nude mouse. In 21 cases the tumor went into remission in the patient and the same response were seen in 19 cases in the nude mouse (90%). When no response was seen in 59 patients the same result was observed in the nude mouse in 57 tumors giving a correct prediction of the xenograft model of 97%. The combination of cytotoxic agents with novel signal transduction inhibitors improved the time to progression and survival time in patients with colorectal (chemo plus Avastin or Cetuximab), non-small cell lung (Avastin) and breast cancers (combo with Herceptin or Avastin). In order to identify suitable xenograft models for such combination studies we investigated the effect of 5FU, Capecitabin, CPT-11 and Oxaliplatin. Treatment started when the sc implanted tumors reached tumor volumes around 5 - 7 mm (about 100 mm³). The compounds where given at their MTD (around LD20 after 2 cycles): 5FU at 100 mg/kg/d ip day 1, 8, 15, Capecitabin 300 mg/kg/d po day 1 to 10 - 14, CPT11 75 mg/kg/d iv day 1 and 8 as well as Oxaliplatin 8 mg/kg day 1,15 ip. All 4 compounds showed high activity mainly in colorectal, mammary and in non-small lung cancer. Capecitabin effected inhibition Overall the activity pattern in the engraft system resembles the activity in the clinic. Suitable models with a moderate sensitivity against the single agent therapy are being selected for combining two-drug cytostatic combinations with Avastin, Cetuximab, and other new signal transduction inhibitors.