Update on gemcitabine and docetaxel combination therapy for primary and metastatic sarcomas

Hensley, Martee L.

doi:10.1097/cco.0b013e32833aafef

Cited by 30 publications

(23 citation statements)

References 29 publications

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“…A later study of 122 patients, 38 (31%) of whom had LMS, showed a response rate of 11% with gemcitabine alone versus 27% in LMS treated with the combination of gemcitabine-docetaxel. The study showed that, for metastatic STS including LMS, OS and PFS were superior with gemcitabine-docetaxel versus gemcitabine alone (17.9 vs 11.5 and 6.2 vs 3.0 months, respectively) [19]. This supported previous trials in advanced STS showing promise for this doublet [18•, 20, 21].…”

Section: Conventional Systemic Therapies For Lmsmentioning

confidence: 69%

“…Many studies have looked at karyotyping for LMS with little consistency, in keeping with the expected heterogeneity and complexity [46]. The chromosomal changes described in LMS include imbalances or aberrations in the form of gains (chromosomes 1, 5, 6, 8, 15, 16, 17, 19, 20, 22, X), losses (chromosomes 1p, 2, 3, 4, 6q, 8, 9, 10p, 11p, 12q, 11q, 13, 16, 17p, 18, 19, 22q), and amplifications (chromosomes 1,5,8,12,13,17,19,20). Some gains and losses of chromosomal material are more frequently observed and tend to correlate with poor outcome, large tumor size, and metastatic disseminationeg, loss of 1p12-pter, 2p, 13q14-q21 (targeting the Rb pathway), 10q (targeting PTEN), and 16q; gains of 17p, 8q, and 5p14 pter [42].…”

Section: Novel Therapeutic Strategiesmentioning

confidence: 99%

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Novel Approaches to Treatment of Leiomyosarcomas

Collins

Thomas

2011

Curr Oncol Rep

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Soft tissue sarcomas are rare tumors and include subtypes with variable clinical, pathological, and genetic characteristics, including leiomyosarcoma. Current chemotherapy options include the use of doxorubicin, ifosfamide, gemcitabine and docetaxel, and trabectedin, but these have poor response rates in the metastatic setting. While some targeted therapies with tyrosine kinase inhibitors have shown promise, there is a clear need for novel, targeted strategies for this enigmatic form of soft-tissue sarcoma. The genomic instability and multiple, complex karyotypic abnormalities of leiomyosarcomas is a potential for therapy with agents with proven activity in other cancers with genomic instability, such as BRCA-related breast or ovarian cancer. There are few pathways affected in leiomyosarcoma that suggest obvious opportunities, but poly ADP-ribose polymerase (PARP) inhibitors hold promise. This article outlines current therapeutic options available and undergoing study, as well as explores the rationale for the study of PARP inhibitors in leiomyosarcomas, with or without chemotherapy.

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Section: Conventional Systemic Therapies For Lmsmentioning

confidence: 69%

Section: Novel Therapeutic Strategiesmentioning

confidence: 99%

Novel Approaches to Treatment of Leiomyosarcomas

Collins

Thomas

2011

Curr Oncol Rep

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“…To the best of our knowledge, this study is the first to evaluate the efficacy and tolerability of G/P in patients with STS. The combination of taxanes and gemcitabine is increasingly utilized in STS, as well as in bone sarcoma (7)(8)(9)15). Early-phase II studies evaluating fixed-dose rate infusion of gemcitabine 900 mg/m 2 administered over 90 min (days 1 and 8) in combination with docetaxel 100 mg/m 2 (day 8) every 21 days, achieved objective response rates of 17-36%, with a median time-to-progression of 5.6-6.2 months (4,7).…”

Section: Discussionmentioning

confidence: 99%

“…While single-agent gemcitabine exhibited only modest activity, the overall response rates in phase II trials combining gemcitabine with docetaxel were in the range of 16-53% in this patient group (3-6). A higher efficacy with superior progression-free survival (PFS) and overall survival (OS) was also demonstrated with this combination in several comparative trials (3,7,8). Therefore, it became common practice in several sarcoma centers to initiate combination treatment, hypothesizing synergy between gemcitabine and docetaxel.…”

mentioning

confidence: 99%

Gemcitabine in combination with paclitaxel for advanced soft-tissue sarcomas

Sonnenblick

Eleyan

Peretz

et al. 2015

Molecular and Clinical Oncology

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Abstract.A limited number of chemotherapeutic agents have been found to be active against advanced soft-tissue sarcomas (STSs), particularly sarcomas that have progressed following doxorubicin treatment. The aim of this retrospective study was to determine the response to treatment with gemcitabine plus paclitaxel in patients with STSs. Data were collected on all patients with advanced non-resectable STS who were treated with a fixed dose 700 mg/m 2 gemcitabine in combination with 70 mg/m 2 paclitaxel on days 1 and 8 every 3 weeks. A total of 30 patients were included, with a median age of 56.4 years (range, 40-70 years). The gemcitabine/paclitaxel combination was well tolerated, with an overall response in 27% and a clinical benefit in 57% of the patients. The median progression-free survival was 6.1 months and the overall survival was 14.3 months. In conclusion, gemcitabine plus paclitaxel was found to be tolerable and effective in patients with advanced STSs. IntroductionSoft-tissue sarcomas (STSs) are a heterogeneous family of malignancies originating from mesenchymal tissues. Patients who present with advanced-stage STS or develop disease recurrence following initial resection carry a poor prognosis, since the majority of chemotherapeutic agents have not achieved any survival benefit in this disease. However, ~30% of patients treated with doxorubicin achieve an objective response and the response rates may increase to 35-40% when doxorubicin is combined with ifosfamide (1,2). The combination of gemcitabine and docetaxel was also proven to be effective in advanced STS, particularly in patients with uterine leiomyosarcoma (LMS) (3). While single-agent gemcitabine exhibited only modest activity, the overall response rates in phase II trials combining gemcitabine with docetaxel were in the range of 16-53% in this patient group (3-6). A higher efficacy with superior progression-free survival (PFS) and overall survival (OS) was also demonstrated with this combination in several comparative trials (3,7,8). Therefore, it became common practice in several sarcoma centers to initiate combination treatment, hypothesizing synergy between gemcitabine and docetaxel. Myelosupression is the primary toxicity (grade 3-4 neutropenia in 17%, grade 3 anemia in 25% and severe thrombocytopenia in 10% of the patients) associated with this type of treatment (9). In addition, grade 3 non-hematological toxicities, including fatigue and myalgia, developed in 25% of the patients. Patients with advanced sarcoma are usually heavily pretreated, with limited bone marrow tolerance and impaired quality of life. Paclitaxel and docetaxel share the same mechanisms of action and were found to exhibit similar efficacies in certain types of cancer, such as breast and lung cancer. Paclitaxel has been proven to be more tolerable when administered weekly, according to studies on breast cancer (10-12). For example, in a prospective randomized trial assessing different schedules and regimens of paclitaxel vs. docetaxel in adjuvant therapy for breast ca...

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“…En l'absence de toxicité cumulative (notamment cardiaque), le doublet de gemcitabine et docétaxel peut permettre un traitement prolongé [7] comme nous l'avons vérifié chez plusieurs de nos patients. Cette action apparaît dans beaucoup de sous-types histologiques plus cytostatique que cytotoxique, à l'instar des nouvelles thérapeutiques ciblées, inhibiteurs de tyrosine-kinase antiangiogéniques [18] ou inhibiteurs de m-TOR [3] dont l'effet antitumoral semble dans l'état actuel des études du même ordre.…”

Section: Réponse Au Traitement Et Survieunclassified