BACKGROUND: The EORTC New Drug Development Office has initiated a multicenter collaborative program to evaluate the use of human tumor xenografts to predict phase II clinical activity. A first study confirmed the efficacy of doxorubicin and inactivity of amsacrine against human tumor xenografts (Boven et al., Cancer Res: 52, 5940, 1992). In the follow-up study reported here, the activities of cisplatin, AZQ (diaziquone), pazelliptine and retelliptine have been evaluated against a panel of 40 established tumor lines grown subcutaneously in nude mice. DESIGN: The xenografts used represent carcinomas of the breast, colon, head+neck, ovary, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and melanoma. Drugs were administered intravenously on days 0 and 7. Doses were for cisplatin 5 mg/kg, AZQ 3-7 mg/kg, pazelliptine 20-80 mg/kg and retelliptine 6-12.5 mg/kg and were selected to give a median loss of about 10%-15% body weight. RESULTS: When activity was defined as a specific growth delay > 1 and a tumor growth inhibition > 50%, then cisplatin demonstrated activity in 15 of 40 xenografts tested (3 of 5 breast, 1 of 6 colon, 0 of 5 head+neck, 2 of 6 NSCLC, 4 of 7 SCLC, 1 of 5 melanoma and 4 of 6 ovarian cancers); AZQ was active in 23 of 38 xenografts (2 of 3 breast, 2 of 7 colon, 4 of 5 head+neck, 3 of 6 NSCLC, 6 of 6 SCLC, 2 of 5 melanoma, 4 of 6 ovarian cancers); pazelliptine was active in 2 of 38 xenografts (1 of 5 breast cancers, 1 of 5 melanoma) while retelliptine was active in 1 of 39 xenografts (a breast cancer xenograft) tested. CONCLUSIONS: These results are reasonably consistent with the clinical activity of cisplatin, but overpredict the clinical efficacy of AZQ. Since pazelliptine and retelliptine are investigational compounds, the clinical phase II studies will provide a prospective test for this model. The results of the present study and the previous one indicate that the human tumor xenograft model could be suitable for predicting the activity of novel compounds to be developed for treatment of cancer patients.
BACKGROUND: The EORTC New Drug Development Office has initiated a multicenter collaborative program to evaluate the use of humantumor xenografts to predict phase II clinical activity. A first study confirmed the efficacy of doxorubicin and inactivity of amsacrine against humantumor xenografts (Boven et al., Cancer Res: 52, 5940, 1992). In the follow-up study reported here, the activities of cisplatin, AZQ (diaziquone), pazelliptine and retelliptine have been evaluated against a panel of 40 established tumor lines grown subcutaneously in nude mice. DESIGN: The xenografts used represent carcinomas of the breast, colon, head+neck, ovary, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC) and melanoma. Drugs were administered intravenously on days 0 and 7. Doses were for cisplatin 5 mg/kg, AZQ 3-7 mg/kg, pazelliptine 20-80 mg/kg and retelliptine 6-12.5 mg/kg and were selected to give a median loss of about 10%-15% body weight. RESULTS: When activity was defined as a specific growth delay > 1 and a tumor growth inhibition > 50%, then cisplatin demonstrated activity in 15 of 40 xenografts tested (3 of 5 breast, 1 of 6 colon, 0 of 5 head+neck, 2 of 6 NSCLC, 4 of 7 SCLC, 1 of 5 melanoma and 4 of 6 ovarian cancers); AZQ was active in 23 of 38 xenografts (2 of 3 breast, 2 of 7 colon, 4 of 5 head+neck, 3 of 6 NSCLC, 6 of 6 SCLC, 2 of 5 melanoma, 4 of 6 ovarian cancers); pazelliptine was active in 2 of 38 xenografts (1 of 5 breast cancers, 1 of 5 melanoma) while retelliptine was active in 1 of 39 xenografts (a breast cancer xenograft) tested. CONCLUSIONS: These results are reasonably consistent with the clinical activity of cisplatin, but overpredict the clinical efficacy of AZQ. Since pazelliptine and retelliptine are investigational compounds, the clinical phase II studies will provide a prospective test for this model. The results of the present study and the previous one indicate that the humantumor xenograft model could be suitable for predicting the activity of novel compounds to be developed for treatment of cancerpatients.
Authors: S John Weroha; Marc A Becker; Sergio Enderica-Gonzalez; Sean C Harrington; Ann L Oberg; Matthew J Maurer; Sarah E Perkins; Mariam AlHilli; Kristina A Butler; Sarah McKinstry; Stephanie Fink; Robert B Jenkins; Xiaonan Hou; Kimberly R Kalli; Karin M Goodman; Jann N Sarkaria; Beth Y Karlan; Amanika Kumar; Scott H Kaufmann; Lynn C Hartmann; Paul Haluska Journal: Clin Cancer Res Date: 2014-01-07 Impact factor: 12.531
Authors: John J Tentler; Aik Choon Tan; Colin D Weekes; Antonio Jimeno; Stephen Leong; Todd M Pitts; John J Arcaroli; Wells A Messersmith; S Gail Eckhardt Journal: Nat Rev Clin Oncol Date: 2012-04-17 Impact factor: 66.675
Authors: Dennis Gürgen; Michael Becker; Mathias Dahlmann; Susanne Flechsig; Elke Schaeffeler; Florian A Büttner; Christian Schmees; Regina Bohnert; Jens Bedke; Matthias Schwab; Johann J Wendler; Martin Schostak; Burkhard Jandrig; Wolfgang Walther; Jens Hoffmann Journal: Front Oncol Date: 2022-06-21 Impact factor: 5.738
Authors: E Boven; H M Pinedo; A H van Hattum; P G Scheffer; W H Peters; C A Erkelens; H M Schlüper; C M Kuiper; J van Ark-Otte; G Giaccone Journal: Br J Cancer Date: 1998-12 Impact factor: 7.640