Soft tissue sarcomas (STS) are a heterogeneous group of malignancies, of mesenchymal origin, encompassing about 50 different subtypes, with a wide spectrum of histological patterns and biological behavior (1,2). Subtypes of STS like leiomyosarcoma, liposarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumour are the most common (3). STS can arise anywhere in the body, but most originate in the extremities, less frequently in the trunk, retroperitoneum, head and neck and viscera. They can occur at any age, including children and young adults, although more common in middle-age and older adults. In recent years,though there have been important advances in the understanding of the pathology and molecular biology of this group of cancers, the advances in the therapeutics have been moderate. About 50% of these tumours develop metastatic recurrences, which are usually fatal, with a median survival ranging from 11 to 18 months from the diagnosis of advanced disease(4-6). As first line, almost 30% of patients treated with doxorubicin and 7-38% patients treated with ifosphamide achieve objective response(7-10).Treatment options for patients with relapsed disease are limited. The role of second line chemotherapy for recurrent STS is much less well defined and there is no accepted standard regimen.Moreover, in advanced STS, the intent of therapy mainly focuses on palliation of symptoms and maintaining an acceptable quality of life.Gemcitabine, as a single agent and in combination with docetaxel have often been used in STS, mainly leiomyosarcomas (a subgroup of STS), where there also have been conflicting results in uterine and non-uterineleiomyosarcomas(11-13).The incidence of many of the individual subtypes of soft tissue sarcoma is too small to permit large-scale prospective randomized controlled trials.

STS are rare,accounting for less than 1% of adult malignancies and 2% of cancer deaths (14). Gastro-intestinal stromal tumors (GIST) is the most common subtype of all sarcomas(15), other common subtypes being leiomyosarcoma, liposarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumour (3). Survival estimates for primary localized STS depend on many factors, including anatomic location and tumour grade(16). Despite treatment almost half of the patients with STS develop recurrent or metastatic disease(4-6, 17,18). For primary resectable STS, surgery is the mainstay of treatment(19,20). For patients with unresectable recurrence or metastatic disease, systemic chemotherapy with conventional cytotoxic agents remains the main treatment modality, the treatment goal being palliation and amelioration of symptoms. The National Comprehensive Cancer Network(19) and the European Society for Medical Oncology(20), recommend anthracyclines (alone or in combination with other agents like ifosphamide) in most cases as first line treatment for metastatic STS.Almost 30% of patients treated with doxorubicin (7,8) and 7-38% patients treated with ifosphamide achieve objective response (9,10). These two drugs represent the large majority of first line treatments.Therapeutic options after failure of doxorubicin and/or ifosphamide are limited and there are no standard recognized therapies. Options include ifosphamide(high dose), trabectadine, gemcitabine in combination with docetaxel or dacarbazine based regimens(18). Seddon et al. conducted a phase II trial to assess the activity of gemcitabine and docetaxel as first line chemotherapy and found significant activity of this combination in first line setting in unresectable leiomyosarcoma(21).Promising anti-tumor activity in patients with metastatic or unresectableSTS has been reported with gemcitabine alone (22,23) docetaxel alone(24)or in combination (25,26).  Leu et al. confirmedbiological evidence of synergistic cytotoxicity(11). The bestresponses have been observed in leiomyosarcoma (LMS) using gemcitabine and docetaxel together, with up to 53% overall response (21, 25). It has often been hypothesized that despite lower response rates, this combinationmight also be efficient with other histological subtypes of sarcomas.The incidence of many of the individual subtypes of soft tissue sarcoma is too small to permit large-scale prospective randomized controlled trials.

 Current practice:

For the majority of STS, there is no evidence that a particular drug sequence is better than another and probably most patients with a good performance status benefit from exposed to a higher number of available regimens. As already mentioned, some STS subtypes are specially sensitive to certain drugs, and this fact could help in selecting the second line therapy, for example, high-dose ifosphamide for synovial sarcoma, trabectedin in myxoidliposarcoma and leiomyosarcoma, gemcitabine with docetaxel or dacarbazine in leiomyosarcoma(27). Studies in the United States(16) and internationally(18) have shown the heterogeneity in treatment patterns in STS following failure of first line therapy.Consequently, the choice of second line and later-line treatment for advanced STS should consider these interventions.  These therapies should also be evaluated for their efficacy/toxicity ratio and other parameters like median overall survival and quality of life.

AIM:To study the outcomes of gemcitabine-docetaxel combination as second-line systemic chemotherapy in patients of recurrent or metastatic soft tissue sarcomas.

OBJECTIVES:

  PRIMARY:To study the objective response rate(ORR) of combination of

Gemcitabine-Docetaxel chemotherapy in patients of metastatic/advanced soft

tissue sarcomas.

SECONDARY:To study the toxicity profile, tolerance, progression free

Survival(PFS), and overall survival(OS) in the study population.

STUDY METHODOLOGY

Study design: Retrospective observational Study (Analysis of clinical profile and laboratory reports of eligible STS patients treated with during study period. at Tata Memorial Centre(TMC), Mumbai.

Patient population: The medical records from the Institutional database of patients of advanced/metastatic soft tissue sarcoma diagnosed at TMH between 01.08.2013and 31.10.2016 and completed at least 3 cycles of chemotherapy with Gemcitabine-Docetaxel combination, in the advanced disease/metastatic setting, and undergone/undergoing response evaluation using either CECT/PET-CT/MRI imaging, with at least 2 months of follow-up data.