Gemcitabine and Docetaxel in Metastatic Sarcoma: Past, Present, and Future

Abstract

Objective. In the era of oral molecular kinase inhibitors, cytotoxic chemotherapy agents are somewhat overlooked, but remain the backbone of treatment for most cancers. Patients with non-gastrointestinal stromal tumor sarcomas, such as leiomyosarcoma, liposarcoma, and undifferentiated high-grade pleomorphic sarcoma (formerly called malignant fibrous histiocytoma), have received doxorubicin and ifosfamide as the backbone of their treatment for over 15 years or more. The goal of this article is to review the data that have led to the use of gemcitabine and docetaxel as a useful combination for patients with metastatic sarcomas, and to comment on possible synergy of the combination.Methods and results. The literature regarding the use of gemcitabine, docetaxel, or both, is reviewed, with emphasis on patients with metastatic sarcoma.Results. Activity of gemcitabine and docetaxel is observed in leiomyosarcoma and undifferentiated highgrade pleomorphic sarcoma. There is apparent schedule dependence of the combination in other cancers; it is unclear if schedule matters in patients with sarcomas. The dose and schedule of gemcitabine and docetaxel examined in phase II studies are probably too high for routine practice.Conclusions. The combination of gemcitabine and docetaxel is an effective option for patients with metastatic sarcoma, increasing the armamentarium for the practicing oncologist in treating this heterogeneous group of diseases. Given the low response rate to docetaxel as a single agent, it is likely that there is true clinical synergy of the combination. The Oncologist 2007;12: 999 -1006 Disclosure of potential conflicts of interest is found at the end of this article.

A Three-Gene Signature for Outcome in Soft Tissue Sarcoma

“…The tumors are relatively resistant to radio and chemotherapy (3,4). Whenever possible patients receive surgery in combination with radiotherapy, second-line treatment, or treatment of metastatic disease, mainly consists of ifosfamide or dacarbazine and doxorubicin, but with limited success and no relevant survival benefit for the combination regimes (5,6). The locally invasive growth and the prognosis determining high rate of metastases often lead to difficulties accomplishing a complete resection.…”

Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial

“…5 The only truly new treatment approved for sarcoma failing standard therapy is trabectedin (approved by the European Medicines Agency in 2007). 6,7 Gemcitabine with dacarbazine or docetaxel [8][9][10] and paclitaxel for angiosarcoma 11 seem to improve progression-free and overall survival in non-randomised and adaptively randomised trials.…”

The Pharmacologic Basis of Ifosfamide Use in Adult Patients with Advanced Soft Tissue Sarcomas

“…This holds true for angiosarcomas of the scull and myxoid/round cell liposarcomas, in which paclitaxel and trabectedin, respectively, induce response rates that are higher than those seen using other compounds. The combination of gemcitabine and docetaxel exhibits antitumor activity against metastatic leiomyosarcomas and undifferentiated high-grade pleiomorphic sarcomas [75]. With respect to ifosfamide, synovial sarcoma in particular is thought to be highly sensitive to this drug, but this is merely based on small series of patients while randomized data are lacking [4,6,69,76,77].…”