Efficacy and Toxicity of Gemcitabine Plus Docetaxel Combination as a Second Line Therapy for Patients with Advanced Stage Soft Tissue Sarcoma

Osman, Kaya Ali; Büyükberber, Süleyman; Özkan, Metin; Alkış, Necati; Sevinç, Alper; Yildirim, Ozdemir Nuriye; Suleyman, Alici; Eşbah, Onur; Berk, Velı; Camcı, Celalettin; Ulas, Arife; Coskun, Ugur; Benekli, Mustafa

doi:10.7314/apjcp.2012.13.2.463

Cited by 13 publications

(5 citation statements)

References 20 publications

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“…4a, b). Next, we examined the differences in the sensitivities to Doxorubicin [20], Gemcitabine [21] and Docetaxel [22] applied to 3D and 2D cultures. Each clone formation of the three drugs was detected in both 2D and 3D cultures of HOSS1 cells (Fig.…”

Section: Resultsmentioning

confidence: 99%

Associations of chemo- and radio-resistant phenotypes with the gap junction, adhesion and extracellular matrix in a three-dimensional culture model of soft sarcoma

Bai

Yang

Fan

et al. 2015

J Exp Clin Cancer Res

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BackgroundThree-dimensional (3D) culture models are considered to recapitulate the cell microenvironment in solid tumors, including the extracellular matrix (ECM), cell-cell interactions, and signal transduction. These functions are highly correlated with cellular behaviors and contribute to resistances against chemo- and radio-therapies. However, the biochemical effects and mechanisms remain unknown in soft sarcoma. Therefore, we developed an in vitro 3D model of sarcoma to analyze the reasons of the chemo- and radio-resistance in therapies.MethodsFour soft sarcoma cell lines, HT1080, RD, SW872, and human osteosarcoma cell line 1 (HOSS1), a cell line established from a patient-derived xenograft, were applied to 3D culture and treated with growth factors in methylcellulose-containing medium. Spheroids were examined morphologically and by western blotting, RT-qPCR, and immunofluorescence staining to analyze cell adhesion, gap junctions, ECM genes, and related factors. Proliferation and colony formation assays were performed to assess chemo- and radio-resistances between 3D and two-dimensional (2D) cell cultures. Annexin V and Propidium Iodide staining was used to detect early apoptotic sarcoma cells treated with Doxorubicin, Gemcitabine, and Docetaxel in the 3D model.ResultsThe four soft sarcoma cell lines formed spheres in vitro by culture in modified condition medium. Compared with 2D cell culture, expression of ECM genes and proteins, including COL1A1, LOX, SED1, FN1, and LAMA4, was significantly increased in 3D culture. Analysis of cadherin and gap junction molecules showed significant changes in the gene and protein expression profiles under 3D conditions. These changes affected cell–cell communication and were mainly associated with biological processes such as cell proliferation and apoptosis related to chemo- and radio-resistances.ConclusionsOur findings revealed significant differences between 3D and 2D cell culture systems, and indicated that cellular responsiveness to external stress such as radiation and chemotherapeutics is influenced by differential expression of genes and proteins involved in regulation of the ECM, cell adhesion, and gap junction signaling.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-015-0175-0) contains supplementary material, which is available to authorized users.

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Section: Resultsmentioning

confidence: 99%

Associations of chemo- and radio-resistant phenotypes with the gap junction, adhesion and extracellular matrix in a three-dimensional culture model of soft sarcoma

Bai

Yang

Fan

et al. 2015

J Exp Clin Cancer Res

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“…Thus, it is possible that the higher incidence of adverse events in >G900/D70 group might associate with the inferior outcome because of discontinuation or dose reduction of GD. It has been reported that approximately half of the patients were required dose reduction of GD because of adverse effects in the previous randomized phase II trials using G900/D100 [18, 21]. Thus, such doses around G900/D100 might be too high for the patients with BSTS.…”

Section: Discussionmentioning

confidence: 99%

“…It has been also reported that GD exhibited higher response rates, progression-free survival (PFS), and overall survival (OS) than single-agent GEM in a randomized phase II trial for patients with advanced STS previously treated by up to three prior regimens [19]. The efficacy of GD as the second-line setting for advanced BSTS was also reported in the prospective and retrospective studies [20, 21]. However, only one study has been reported showing the effects of GD as adjuvant or first-line treatment on BSTS [22].…”

Section: Introductionmentioning

confidence: 93%

Feasibility and efficacy of gemcitabine and docetaxel combination chemotherapy for bone and soft tissue sarcomas: multi-institutional retrospective analysis of 134 patients

et al. 2016

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BackgroundBone and soft tissue sarcomas (BSTS) are rare malignant tumors. Recently, the combination of gemcitabine and docetaxel (GD) was shown to have activity as second-line setting in BSTS. However, the efficacy as first-line and adjuvant settings and precise profiles of adverse events in Japanese patients are not known yet. In the present study, the feasibility and efficacy of GD in patients with BSTS were investigated.MethodsPatients with BSTS treated with GD in our institutions were retrospectively analyzed. Information regarding clinical features, adverse events, and outcome was collected and statistically studied. Factors related to survival were analyzed using log-rank test and Cox proportional hazard regression method.ResultsA total of 134 patients were analyzed. GD was carried out as adjuvant setting in 9, first-line in 23, second-line in 56, and third-or-greater line in 46 patients. The response rate (RR) for all patients was 9.7%. RR for the patients treated as adjuvant or first-line setting was 18.8%, whereas that as second-or-greater line was 6.9%. The median progression-free survival (PFS) and overall survival (OS) of all patients were 4.8 (95% CI 3.5–6.1) and 16.4 (95% CI 9.8–22.9) months, respectively. Survival tended to be better in the patients treated as first-line than in those treated as second-or-greater line. Multivariate analysis demonstrated that history of prior chemotherapy (p = 0.046) and response to GD (p = 0.009) was significantly associated with PFS and OS, respectively. The leucopenia and neutropenia were the most frequent adverse events, and grade 3 or 4 leucopenia and neutropenia were observed in 69.4 and 72.4% of the patients. Grade 2 or 3 pneumonitis was observed in one (0.7%) and four (3.0%) patients, respectively. All the patients with pneumonitis had experienced prior chemotherapy and/or radiotherapy.ConclusionsGD used as both first- and second/later line is effective chemotherapy for a proportion of patients with advanced BSTS. Higher response rate and better outcome was achieved in chemotherapy-naïve patients. This regimen is associated with high incidence of severe hematological toxicity, as well as the risk of severe pneumonitis, especially in pre-treated patients. GD is promising for further analysis by phase III study for the patients with BSTS.

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“…We were also unable to systematically collect data regarding the toxicity of Gem/Doce and patients' quality of life. The main aim of this study was to investigate the efficacy of Gem/Doce in ES, since the adverse events and toxicity profile have been well described in other studies [21,23,24,25,26]. The most frequently occurring adverse events were hematologic, with some patients requiring a dose reduction.…”

Section: Discussionmentioning

confidence: 99%

“…Combination regimens using gemcitabine and docetaxel (Gem/Doce) have proven to be effective in STS, especially when used in uterine and nonuterine leiomyosarcoma [21,22,23,24], but are formally not approved for STS treatment. Thus far, there are no available data on the efficacy of Gem/Doce for ES.…”

Section: Introductionmentioning

confidence: 99%

Gemcitabine and Docetaxel for Epithelioid Sarcoma: Results from a Retrospective, Multi-Institutional Analysis

Pink¹,

Richter

Gerdes

et al. 2014

Oncology

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Objective: Epithelioid sarcoma (ES) presents unique clinical features in comparison to other sarcoma subtypes. Data regarding the benefits of chemotherapy are very limited. Combination regimens using gemcitabine and docetaxel (Gem/Doce) have proven to be effective, especially in uterine and nonuterine leiomyosarcoma. Yet, there is no available data on the efficacy of Gem/Doce in ES. Methods: A retrospective analysis of the three participating institutions was performed. Twenty-eight patients with an ES diagnosis presented at one of the participating institutions between 1989 and 2012. Of this group, 17 patients received chemotherapy. Results: Patients' median overall survival (OS) after the beginning of palliative chemotherapy was 21 months, and the 1-year OS was 87%. Twelve patients received Gem/Doce with a clinical benefit rate of 83%. The median progression-free survival (PFS) was 8 months for all patients receiving Gem/Doce. The best response was complete remission in 1 patient and partial remission in 6 patients. All 6 patients receiving Gem/Doce as a first-line treatment showed measurable responses with a median PFS of 9 months. Conclusions: In this retrospective study, Gem/Doce was an effective chemotherapeutic regimen for ES. Prospective studies are needed to better assess the effects of this combination drug therapy.

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Efficacy and Toxicity of Gemcitabine Plus Docetaxel Combination as a Second Line Therapy for Patients with Advanced Stage Soft Tissue Sarcoma

Cited by 13 publications

References 20 publications

Associations of chemo- and radio-resistant phenotypes with the gap junction, adhesion and extracellular matrix in a three-dimensional culture model of soft sarcoma

Associations of chemo- and radio-resistant phenotypes with the gap junction, adhesion and extracellular matrix in a three-dimensional culture model of soft sarcoma

Feasibility and efficacy of gemcitabine and docetaxel combination chemotherapy for bone and soft tissue sarcomas: multi-institutional retrospective analysis of 134 patients

Gemcitabine and Docetaxel for Epithelioid Sarcoma: Results from a Retrospective, Multi-Institutional Analysis

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