Artikel
Anticancer activity of Erbitux® in 60 human tumor xenograft models
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Veröffentlicht: | 20. März 2006 |
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Gliederung
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Erbitux® (Cetuximab), an antibody against human EGFR has shown convincing activity in clinical trials in combination with cytotoxic drugs. It was registered for second line therapy of colon cancer. We have investigated Erbitux® in a panel of patient derived tumor models established sc in nude mice and compared the degree of activity with clinical responses. Erbitux® was injected ip at 30 mg/kg once weekly for three weeks. A total of 60 tumors were included: NSCLC (22), colon (13), mammary (10), renal cancers (4), and 11 of other tumor types. Overall, Erbitux® effected an inhibition to < 25 % of the control in 10 tumors (17%), inhibition to T/C 25 – 42 % in another 5 models (8%) whereas 45 tumors (75%) were resistant (T/C > 42 %). Inhibition with T/C values < 42% were observed in 4/13 colon models and 6/22 NSCLC. 4/4 renal and 9/10 mammary cancers were resistant to treatment with Erbitux® . The NSCLC and colon cancers responded against this single agent therapy as found in clinical trials where Erbitux® increased the survival times significantly. Remissions (T/C values <10%) were found in 3 NSCLC, 2 colon and 1 gastric cancer model. In 2 NSCLC and 1 colon cancer model even complete remission lasting up to 3 months was observed. The remaining sensitive tumors with T/C values between 14 and 41% should be suitable tumor models for further combination studies. The tumors were characterized for micro vessel density, vascular porosity and, using tumor cell lysates, for the production of EGFR and P-EGFR. Besides the activity in colon and NSCLC Erbitux® was also active in 1/1 head and neck cancer (T/C 29%), in 1/2 gastric (T/C 7%) and in 1/3 pancreas carcinoma models. In conclusion human tumor xenograft models of colon, NSCLC, and 1 head and neck cancer responded to Erbitux® monotherapy, i. e. activity was found in the same tumor types in which Erbitux® in combination with cytotoxic drugs significantly increased the survival times in the clinic.