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Molecular Cancer Therapeutics
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Spotlight on Clinical Response

A Pilot Clinical Study of Treatment Guided by Personalized Tumorgrafts in Patients with Advanced Cancer

Manuel Hidalgo, Elizabeth Bruckheimer, N.V. Rajeshkumar, Ignacio Garrido-Laguna, Elizabeth De Oliveira, Belen Rubio-Viqueira, Steven Strawn, Michael J. Wick, James Martell and David Sidransky
Manuel Hidalgo
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Elizabeth Bruckheimer
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N.V. Rajeshkumar
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Ignacio Garrido-Laguna
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Elizabeth De Oliveira
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Belen Rubio-Viqueira
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Steven Strawn
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Michael J. Wick
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James Martell
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David Sidransky
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DOI: 10.1158/1535-7163.MCT-11-0233 Published August 2011
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    Figure 1.

    Clinical outcome of patient CBI-0803 and response to anticancer agents in patient's xenografts. A, time course of CEA levels. B, tumor growth curve of patient's personalized tumorgraft, treated with the indicated agents at the dose and schedules. C and D, CT scan of the abdomen, before and after treatment with irinotecan-cetuximab and bevacizumab, showing a marked decrease in tumor volume. E, tumor growth curve of patient's tumor treated with the indicated agents.

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    Figure 2.

    Clinical outcome of patient CBI-0805 and remarkable antitumor potential of irinotecan in patient's xenografts. A, response of patient's tumorgraft to single-agent irinotecan illustrates a complete eradication of the tumor. B, CT scan of pelvis before treatment. C, CT scan of pelvis showing a significant reduction in a metastatic pelvic mass. D, intratumor concentration of irinotecan and SN38 in this patient's xenograft and an irinotecan-resistant colorectal cancer (CRC) tumorgraft (CRC-005), showing heightened retention of SN38 in CBI-0805.

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  • Table 1.

    Patient characteristics and outcome of treatments based on xenograft predictions

    Identification numberGenderAge (years)TumorXenograftPrior systemic therapySystemic therapy administered on the basis of xenograft dataResponseDuration of response (months)
    JH033Male63Pancreatic ductal adenocarcinomaPrimary tumorGemcitabineMitomycin C, cisplatinPR50+
    JH082Female64Pancreatic ductal adenocarcinomaPrimary tumorNoneGemcitabineProgressive disease
    JH102Female66Pancreatic ductal adenocarcinomaPrimary tumorNoneGemcitabineStable disease
    JH161Female70Pancreatic ductal adenocarcinomaPrimary tumorNoneGemcitabineStable disease
    CBI-0601Female55LeiomyosarcomaPelvic metastasisAdriamycin, ifosfamideGemcitabine, docetaxel, bevacizumabPR9
    Gemcitabine, doxetaxelCapcetabine, temozlomidePR9
    CBI-0602Male45Mesenchymalchondro sarcomaLung mestastasisVACDocetaxel, irinotecan, bevacizumabPR9
    SunitinibStable disease4
    CBI-0603Male50Non–small cell lung carcinomaPrimary tumorCarboplatin, paclitaxelSorafenib, irinotecan, bevacizumabPR9
    PemetrexedNo response
    CBI-0701Male36MyoepitheliomaPrimary tumorNoneDoxorubicin, cisplatinProgressive disease
    ImatinibProgressive disease
    Carboplatin-bevacizumabProgressive disease
    CBI-0803Male54Esophageal adenocarcinomaLiver metastasisEpirubicin, 5-fluorouracil, cisplatinIrinotecan-cetuximab- bevacizumabPR14
    Abraxane-avastinPR9
    Ixabepilone-avastinPR9
    Ixabepilone-navelbinePR6+
    CBI-0805Female44Colon adenocarcinomaLiver metastasisFOLFOXIrinotecanPR14
    Capecitabine, lapatanibPR6+
    CBI-0810Female36Breast cancerLiver metastasis5-fluorouracil, cyclophosphamiirinotecan, bevacizumabNoneNo response
    No response
    CBI-0901Male49RhabdomyosarcomaLung metastasisNoneDocetaxel, gemcitabine, bevacizumabPR8
    CBI-0907Female62ColonLiver metstasisFOLFOXCetuximab, irinotecanPR6
    IrinotecanPR15
    CBI-0914Male58MelanomaLung metastasisNoneB-raf inhibitorPR6

    Note: When tumorgrafts reached approximately 150 mm3, animals were randomized (5 mice with tumors on both flanks per group) and dosing initiated. Details on drugs, doses, and schedules are provided in Supplementary Table S1.

    Abbreviations: VAC, vinblastine, doxorubicin and cisplatin; FOLFOX, folinic acid, 5-fluorouracil, oxaliplatin.

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    Molecular Cancer Therapeutics: 10 (8)
    August 2011
    Volume 10, Issue 8
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    A Pilot Clinical Study of Treatment Guided by Personalized Tumorgrafts in Patients with Advanced Cancer
    Manuel Hidalgo, Elizabeth Bruckheimer, N.V. Rajeshkumar, Ignacio Garrido-Laguna, Elizabeth De Oliveira, Belen Rubio-Viqueira, Steven Strawn, Michael J. Wick, James Martell and David Sidransky
    Mol Cancer Ther August 1 2011 (10) (8) 1311-1316; DOI: 10.1158/1535-7163.MCT-11-0233

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    A Pilot Clinical Study of Treatment Guided by Personalized Tumorgrafts in Patients with Advanced Cancer
    Manuel Hidalgo, Elizabeth Bruckheimer, N.V. Rajeshkumar, Ignacio Garrido-Laguna, Elizabeth De Oliveira, Belen Rubio-Viqueira, Steven Strawn, Michael J. Wick, James Martell and David Sidransky
    Mol Cancer Ther August 1 2011 (10) (8) 1311-1316; DOI: 10.1158/1535-7163.MCT-11-0233
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