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.
SourceAvailable from: Salvatore Provenzano[Show abstract] [Hide abstract]
ABSTRACT: Conventional skeletal chondrosarcoma is a bone neoplasm, which is poorly sensitive to anthracyclines-based chemotherapy. We report on an 18-month-long tumour response to gemcitabine as single agent in a young patient with an advanced secondary peripheral conventional chondrosarcoma, previously treated unsuccessfully with anthracyclines, ifosfamide, platinum, etoposide.03/2015; 2015(5):9. DOI:10.1186/s13569-015-0025-z
[Show abstract] [Hide abstract]
ABSTRACT: Introduction: Pharmacological treatment plays a major role in the management of advanced, persistent or recurrent uterine leiomyosarcoma (LMS), whereas its usefulness in the adjuvant setting is still debated. A thorough literature search was undertaken using the Pubmed databases. Systematic reviews and controlled trials on medical treatment of uterine LMS were collected and critically analyzed. Other study types were secondarily considered when pertinent. Areas covered: Doxorubicin (DOX), ifosfamide and dacarbazine have been long used in the treatment of this malignancy. Novel active agents are represented by gemcitabine, docetaxel, trabectedin, pazopanib and aromatase inhibitors, whereas the role of eribulin, bevacizumab, aflibercept and mammalian target of rapamycin inhibitors is still investigational. Expert opinion: DOX alone, gemcitabine alone, DOX + dacarbazine and gemcitabine + docetaxel may be treatment options for first-line and second-line therapies. However, the clinical benefit of the combination chemotherapy versus single-agent chemotherapy is still debated. Trabectedin is a promising agent for recurrent uterine LMS, able to obtain a prolonged disease control, with 3-month and 6-month progression-free survival rates exceeding 50 and 30%, respectively, and with sometimes unexpectedly durable responses. Pazopanib is the only approved targeted therapy. Hormone therapy with aromatase inhibitors may be a therapeutic option in heavily treated patients with slowly progressive, steroid receptor-positive tumors. Whenever possible, women with recurrent uterine LMS should be encouraged to enter well-designed clinical trials aimed to detect novel active agents.Expert Opinion on Pharmacotherapy 11/2014; 16(3):1-12. DOI:10.1517/14656566.2015.985205 · 3.09 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Retroperitoneal leiomyosarcomas (LMSs) are rare gynecological malignancies that display poor prognosis and high mortality. Cell cycle-related and expression-elevated protein in tumor (CREPT) is an oncogene that is involved in the regulation of many cell cycle-related proteins. However, its distribution and clinical significance in retroperitoneal LMS remains poorly understood. This study assessed the histological classifications of postoperative tumor samples from 71 cases of retroperitoneal LMS that were collected at The General Hospital of the People's Liberation Army from January 1998 to December 2012. We found that more than half of the patients displayed positive expressions of CREPT, Ki-67 and PCNA via immunohistochemical analysis. The expression of CREPT correlated with histological grade (P = 0.044), and the PCNA expression level correlated with the differentiation of tumor cells and histological grade (P < 0.001 and P = 0.009, respectively). Multivariate analysis showed that survival was associated with histological grade and the expression level of CREPT (P = 0.011 and P = 0.012, respectively). Kaplan-Meier analysis showed that the patients lacking CREPT expression exhibited significantly longer overall postoperative survival (median, 60.0 months) than the patients displaying CREPT expression (median, 33.0 months), and CREPT expression correlated with distant recurrence within 5 years after surgery (P = 0.004). Western blot analyses showed that CREPT was more strongly expressed in the retroperitoneal LMS tumor tissue than in paired control tissue. Based on the above data, we concluded that CREPT displays unique immunostaining for retroperitoneal LMS tissue and can be used to supplement other currently available retroperitoneal LMS markers.