Randomized Multicenter and Stratified Phase II Study of Gemcitabine Alone Versus Gemcitabine and Docetaxel in Patients with Metastatic or Relapsed Leiomyosarcomas: A Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) French Sarcoma Group Study (TAXOGEM study).
ABSTRACT Background. This study aimed to evaluate the efficacy and toxicity of single-agent gemcitabine versus gemcitabine plus docetaxel as second-line therapy in patients with uterine and nonuterine leiomyosarcoma (LMS). Patients and Methods. Patients had metastatic or unresectable LMS and had received one prior anthracycline-based regimen. A total of 90 patients received either single-agent gemcitabine (arm A; gemcitabine, 1,000 mg/m(2) i.v. for 100 minutes on days 1, 8, and 15 of a 28-day cycle) or a combination of gemcitabine and docetaxel (arm B; gemcitabine, 900 mg/m(2) i.v. for 90 minutes on days 1 and 8, plus docetaxel, 100 mg/m(2) i.v. for 1 hour on day 8 of a 21-day cycle with lenograstim). The primary endpoint was the objective response rate. Results. The objective response rates were 19% and 24% in arm A (gemcitabine) and arm B (gemcitabine plus docetaxel), respectively, for patients with uterine LMS. For patients with nonuterine LMS, the objective response rates were 14% and 5% for arms A and B, respectively. The median progression-free survival times for arms A and B were 5.5 months and 4.7 months, respectively, for patients with uterine LMS. For patients with nonuterine LMS, the median progression-free survival times were 6.3 months and 3.8 months for arms A and B, respectively. One toxic death occurred in arm B. Conclusions. Both single-agent gemcitabine and gemcitabine plus docetaxel were found to be effective second-line therapies for leiomyosarcomas, with a 3-month progression-free survival rate of 40% for LMS with both uterine and nonuterine sites of origin. Single-agent gemcitabine yielded results similar to those of gemcitabine plus docetaxel in this trial, but patients using single-agent gemcitabine experienced less toxicity.
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ABSTRACT: Background Gemcitabine and docetaxel have been shown to be active in pre-treated relapsed leiomyosarcoma. This study investigated the combination as first line treatment in patients with unresectable locally advanced/metastatic leiomyosarcoma. Methods Patients received gemcitabine 900 mg/m2 days 1 and 8, and docetaxel 100 mg/m2 day 8, administered 3-weekly for up to 8 cycles, with GCSF support on days 9–15. Patients who had received previous radiotherapy were treated at 75% dose. Patients were evaluated for response by RECIST 1.0 after cycles 2, 4, 6 and 8, and 3-monthly after completing treatment. Results Forty-four patients were evaluable for response. Eligible patients had histologically proven leiomyosarcoma of the uterus (54.5%) or other sites (45.5%). Thirty-nine patients (84.4%) had metastatic disease, and 5 (15.6%) had locally advanced disease. Six patients (13.6%) had grade 1 disease, and 23 (75%) had grade 2/3 disease. All patients had demonstrated disease progression prior to trial entry. Responses were as follows: partial response 11 (25.0%), stable disease (confirmed) 16 (36.6%), stable disease (unconfirmed) 7 (15.9%), progressive disease 10 (22.7%). Median progression-free survival and overall survival were 7.1 months (95% CI 5.7–8.3) and 17.9 months (95% CI 10.6–25.2), respectively. Progression free rates at 3 and 6 months were 70.5% (95% CI 56.7–84.2%) and 59.1% (95% CI 44.3–73.9%). Conclusions This study demonstrates gemcitabine and docetaxel to be active in locally advanced/metastatic leiomyosarcoma in the first line setting. Further investigation comparing with current standard therapies for leiomyosarcoma is warranted.05/2015; 5(1). DOI:10.1186/s13569-015-0029-8
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ABSTRACT: Sarcomas are a rare family of heterogeneous tumors of mesenchymal origin characterized by their bad prognosis. In addition, limited active therapeutic options are available. The cytotoxic drug gemcitabine and the inhibition of the mTOR pathway have demonstrated modest activity in sarcomas as monotherapy. However, preclinical data suggest that the combination of both treatments results in enhanced antitumor activity. In vitro and in vivo experiments with the mTOR inhibitor sirolimus plus gemcitabine showed dramatic results in preclinical models of sarcoma. Moreover, a Phase I study demonstrated the favorable toxicity profile of the combination in patients with advanced solid tumors. Therefore, treatment with sirolimus plus gemcitabine deserves further investigation in sarcomas.Expert Review of Anticancer Therapy 01/2015; 15(3):1-3. DOI:10.1586/14737140.2015.1003045 · 3.06 Impact Factor
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ABSTRACT: To investigate the clinical and histopathological characteristics, with the prognostic factors, treatment outcome, pattern of relapse, and survival analysis of uterine sarcoma patients.Saudi medical journal 10/2014; 35(10):1215-22. · 0.55 Impact Factor