Dataset Information

Prospective study of the evolution of blood lymphoid immune parameters during dacarbazine chemotherapy in metastatic and locally advanced melanoma patients.

ABSTRACT:

Background

The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans.

Methods

In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests.

Results

We found that chemotherapy induces lymphopenia and that a significantly higher numbers of naïve CD4+ T cells and lower proportion of Treg before chemotherapy are associated with disease control after dacarbazine treatment. Interestingly, NK cell cytotoxicity against dacarbazine-pretreated melanoma cells is only observed in NK cells from patients who achieved disease control.

Conclusion

Together, our data pinpoint that some immune factors could help to predict the response of melanoma patients to dacarbazine. Future larger scale studies are warranted to test their validity as prediction markers.

SUBMITTER: Mignot G

PROVIDER: S-EPMC4149472 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Publications

Prospective study of the evolution of blood lymphoid immune parameters during dacarbazine chemotherapy in metastatic and locally advanced melanoma patients.

Mignot Grégoire G Hervieu Alice A Vabres Pierre P Dalac Sophie S Jeudy Geraldine G Bel Blandine B Apetoh Lionel L Ghiringhelli François F

PloS one 20140829 8

<h4>Background</h4>The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans.<h4>Methods</h4>In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assess ...[more]

PMID: 25170840

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Project description:Chemotherapy still plays an important role in metastatic melanoma, particularly for patients who are not suitable or have no access to highly efficacious new therapies. Pre-therapeutic chemosensitivity testing might be useful to identify optimal chemotherapy regimens for individual patients. This multicenter randomized phase-3 trial was aimed to test for superiority of chemosensitivity-directed combination chemotherapy compared to standard dacarbazine monochemotherapy, and to demonstrate the chemosensitivity test result as prognostic in metastatic melanoma. Chemo-naive patients with advanced melanoma were biopsied from metastatic lesions. Tumor cells were isolated and tested ex-vivo for sensitivity to chemotherapeutic agents using an ATP-based viability assay. Patients with evaluable test results were randomly assigned to receive either chemosensitivity-directed combination chemotherapy (paclitaxel+cisplatin, treosulfan+gemcitabine, treosulfan+cytarabine), or dacarbazine. The primary study endpoint was overall survival (OS). After inclusion of 287 patients and a median follow-up of 26 months, the per-protocol population (n=244) showed no difference in OS between chemosensitivity-directed therapy and dacarbazine (median 9.2 vs 9.0 months, HR=1.08, p=0.64). The disease control rate (CR+PR+SD) tended to be higher in patients treated with chemosensitivity-directed therapy (32.8% vs 23.0%, p=0.088); objective response rates (CR+PR) showed no difference between groups (10.7% vs 12.3%, p=0.90). Patients whose tumors were tested chemosensitive showed no better OS or response rate than patients with chemoresistant tumors. Severe toxicities (CTC grade 3-4) were significantly more frequently observed with chemosensitivity-directed combination chemotherapy than with dacarbazine (40.2% vs 12.3%, p<0.0001). These results indicate, that chemosensitivity-directed combination chemotherapy is not superior to dacarbazine, but leads to significantly more severe toxicities.

Dataset Information

Prospective study of the evolution of blood lymphoid immune parameters during dacarbazine chemotherapy in metastatic and locally advanced melanoma patients.

Background

Methods

Results

Conclusion

Publications

Prospective study of the evolution of blood lymphoid immune parameters during dacarbazine chemotherapy in metastatic and locally advanced melanoma patients.

Similar Datasets

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