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Thread: Chemosensitivity Testing in soft tissue sarcomas

  1. #1
    Distinguished Community Member gpawelski's Avatar
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    Default Chemosensitivity Testing in soft tissue sarcomas

    Feasibility of chemosensitivity testing in soft tissue sarcomas

    Marcus Lehnhardt (1), Thomas Muehlberger (1), Cornelius Kuhnen (2), Daniel Brett (1), Hans U Steinau (1), Hamid J Jafari (1), Lars Steinstraesser (1), Oliver Müller (3) and Heinz H Homann (1)

    (1) Department of Plastic Surgery, Burn Center, Hand surgery, Sarcoma Reference Center, BG University Hospital Bergmannsheil, Ruhr University Bochum, Bürkle-de-la Camp Platz 1, 44789 Bochum, Germany

    (2) Institute of Pathology, BG University Hospital Bergmannsheil, Ruhr University Bochum, Germany

    (3) Tumor Genetics Group, Max-Planck-Institut für molekulare Physiologie, Dortmund, Germany

    Abstract

    Background:

    Soft tissue sarcomas comprise less than 1% of all solid malignancies. The presentation and behavior of these tumors differs depending on location and histological characteristics. Standard therapy consists of complete surgical resection in combination with adjuvant radiotherapy. The role of chemotherapy is not clearly defined and is largely restricted to clinical trials. Only a limited number of agents have proved to be effective in soft tissue sarcomas. The use of doxorubicin, epirubicin and ifosfamide allowed response rates of more than 20%. In addition, recent chemotherapy trials did not demonstrate any significant differences in efficacy for various histological subtypes.

    Methods:

    The objective of this study was to gain additional information about the chemosensitivity of soft tissue sarcomas to seven 7 different chemotherapy agents as single drugs and 4 combinations. Therefore we used an established ATP based in-vitro testing system and examined 50 soft tissue sarcomas. Chemosensitivity was assessed using a luciferin-luciferase-based luminescence assay providing individual chemosensitivity indices for each agent tested.

    Results:

    The sensitivity varied widely according to the histological subtypes. The tumors state of cellular dedifferentiation played a crucial role for the efficiency of the chemotherapeutic agents. The sensitivity also depended on the presentation of the sarcoma as a primary or recurrent tumor. The highest sensitivity was demonstrated for actinomycin D as a single agent, with 74% of the tumor samples exhibiting a high-grade sensitivity (20% low sensitivity, no resistance). The combination of actinomycin D and ifosfamide yielded a high sensitivity in 76% (2% resistance). Doxorubicin as a mono-therapy or in combination with ifosfamide achieved high sensitivity in 70% and 72%, respectively, and resistance in 6% of the samples.

    Conclusion:

    Chemosensitivity testing is feasible in soft tissue sarcomas. It can be used to create sensitivity and resistance profiles of established and new cytotoxic agents and their combinations in soft tissue sarcomas. Our data demonstrate measurable discrepancies of the drug efficiency in soft tissue sarcomas, sarcoma subtypes and tumor recurrencies. However, current therapeutic regime does not take this in consideration, yet.

    World Journal of Surgical Oncology 2005, 3:20 doi:10.1186/1477-7819-3-20

    http://www.wjso.com/content/3/1/20/abstract
    Gregory D. Pawelski

  2. #2
    Distinguished Community Member gpawelski's Avatar
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    Default Chemosensitivity Testing at the Highest Level

    Ugurel S, Schadendorf D, Pfohler C, Neuber K, Thoelke A, Ulrich J, Hauschild A, Spieth K, Kaatz M, Rittgen W, Delorme S, Tilgen W, Reinhold U; Dermatologic Cooperative Oncology Group

    Skin Cancer Unit, German Cancer Research Center Heidelberg and Department of Dermatology, University Hospital of Mannheim, Mannheim, Germany.

    PURPOSE:

    In vitro sensitivity assays are promising tools to predict the individual outcome of different chemotherapy regimens. However, a direct association between in vitro and in vivo chemosensitivity has to be shown by clinical studies. This multicenter phase II trial was aimed to investigate the efficacy of a sensitivity-directed, first-line chemotherapy in metastasized melanoma patients, and to prove an association between in vitro sensitivity and therapy outcome.

    PATIENTS AND METHODS:

    The primary study end point was objective response; secondary end points were safety, overall survival, and progression-free survival. Viable tumor cells obtained from metastatic lesions were tested for chemosensitivity to seven single drugs and five drug combinations using an ATP-based luminescence viability assay.

    RESULTS:

    Out of 82 recruited patients (intention-to-treat), 57 received assay-directed chemotherapy and 53 were evaluable for all study end points (per protocol). The drug combinations used were gemcitabine+treosulfan, paclitaxel+cisplatin, paclitaxel+doxorubicin, and gemcitabine+cisplatin. The per protocol population could be divided into 22 (42%) chemosensitive and 31 (58%) chemoresistant patients by an arbitrary chemosensitivity index. Objective response was 36.4% in chemosensitive patients compared with 16.1% in chemoresistant patients (P=0.114); progression arrest (complete response+partial response+stable disease) was 59.1% versus 22.6% (P=0.01). Chemosensitive patients showed an increased overall survival of 14.6 months compared with 7.4 months in chemoresistant patients (P=0.041).

    CONCLUSION:

    In vitro chemosensitivity testing may be worthy of further exploration to see if it could be a useful tool to predict the outcome of melanoma patients treated with a sensitivity-directed chemotherapy. Therefore, these preliminary results will be evaluated by a planned phase III trial using a randomized, standard-regimen controlled setting.

    Clin Cancer Res. 2006 Sep 15;12(18):5454-63.

    http://www.lance.de/lance/gb_content..._full_1_7.html
    Last edited by Mike Weins; 10-19-2011 at 08:33 AM. Reason: after tweaking word filter, entered name of drug (paclitaxel)
    Gregory D. Pawelski

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    Distinguished Community Member gpawelski's Avatar
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    Default Chemosensitivity-assay-directed therapy influence on prognosis of patient stage IV

    Does chemosensitivity-assay-directed therapy have an influence on the prognosis of patients with malignant melanoma stage IV? A retrospective study of 14 patients with malignant melanoma stage IV.

    Doerler M, Hyun J, Venten I, Potthoff A, Bartke U, Serova K, Hoextermann S, Altmeyer P, Brockmeyer NH.

    Department of Dermatology, Ruhr-University Bochum, Germany.

    Abstract

    OBJECTIVE:

    To evaluate the efficacy of chemosensitivity-testing directed chemotherapy in comparison with empirically chosen therapy regimens in patients with malignant melanoma stage IV.

    PATIENTS AND METHODS:

    Retrospective study including 14 patients with histologically confirmed malignant melanoma and diagnosis of stage IV disease by routine diagnostic procedures. Patients in group A (n = 7) were treated according to their individual chemosensitivity testing results, whereas patients in group B (n = 7) received empirically chosen treatment regimens. Chemosensitivity testing was performed using a nonclonogenic ATP-TCA assay. For statistical analysis the Kaplan-Meier method was used to calculate survival curves. The log-rank test was performed to compare the overall survival according to treatment group, LDH level in serum and AJCC-category. To compare the distribution of sex, LDH level in serum and AJCC-category between the treatment groups, the Fisher exact test was used.

    RESULTS:

    The median overall survival of group A exceeded the median overall survival of group B by 8 versus 3 months, respectively with a median overall survival of 5 months for the whole study population. LDH level in serum at study entry showed a strong correlation with overall survival, with normal LDH levels leading to a statistically significant longer survival (p = 0.006 for the log-rank test, respectively). Moreover, stage AJCC M1a/b yielded to a better prognosis compared with stage AJCC M1c (log-rank test p = 0.066; not statistically significant).

    CONCLUSION:

    Chemosensitivity-assay directed therapy might be a useful tool in determining the optimized chemotherapeutic drug or drug combination in the individual patient and might contribute to a better prognosis in patients with metastatic melanoma stage IV.

    Eur J Med Res. 2007 Oct 30;12(10):497-502 PMID:18024256

    http://www.ncbi.nlm.nih.gov/pubmed/18024256

    http://www.daignet.de/site-content/d...fs/Doerler.pdf

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    Gregory D. Pawelski

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