[An Effective Treatment of Relapsed Leiomyosarcoma with Fourth-Line Trabectedin].

A 56-year-old women underwent retroperitoneal leiomyosarcoma resection in December 2011. In July 2015, CT showed multiple liver metastases, and she received first-line chemotherapy treatment with doxorubicin. After 2 courses of doxorubicin, her performance status deteriorated; therefore, she was treated with pazopanib as second-line chemotherapy. PFS with pazopanib was 5 months and that with eribulin was 2.5 months. She was then treated with trabectedin as fourth-line chemotherapy from July 2016. The liver metastases reduced, and the disease was controlled for 1 year and 6 months following administration of trabectedin. We continue to treat this patient with trabectedin, and no serious side effects have been observed.

Efficacy and safety of trabectedin as an early treatment for advanced or metastatic liposarcoma and leiomyosarcoma.

AIMS: We aimed to evaluate the effect of prior chemotherapies on the outcomes of patients with liposarcoma and leiomyosarcoma treated with trabectedin as a 24-h infusion every 3 weeks. PATIENTS & METHODS: Data from 129 patients who received trabectedin as second-line treatment following failure with an anthracycline/ifosfamide and those who had received at least two lines of prior chemotherapy were analyzed. RESULTS: Forty seven patients received one prior regimen (group A) and 82 patients received at least two lines of chemotherapy (group B). A favorable trend in median time to progression (4.4 vs 3.0 months), progression-free survival (4.4 vs 2.6 months) and overall survival (17.4 vs 13.3 months) was found in group A. A trend toward higher overall response rate (6.4 vs 4.9%) and disease control rate (34.0 vs 26.8%) also favored group A. Both groups had equivalent safety profiles. CONCLUSION: All efficacy outcomes were better in patients who received trabectedin as second-line treatment compared with patients with more extensive prior therapy.

Prolonged disease stability with trabectedin in a heavily pretreated elderly patient with metastatic leiomyosarcoma of the thigh and renal failure: a case report and review of the literature.

Leiomyosarcoma represents about 24% of all soft tissue sarcomas and can originate from retroperitoneum, uterus, or extremities. Adequate local control may be achieved with surgery and radiotherapy. In the presence of unresectable metastases either doxorubicin- or gemcitabine-based chemotherapy is the standard of treatment. Nevertheless, prognosis remains poor regardless of the selected chemotherapy regimen, and new effective therapeutic agents for patients with advanced leiomyosarcoma are needed. Trabectedin, a promising new DNA-damaging agent with a mechanism of action that is different from that of traditional alkylating agents, is approved in Europe for the treatment of patients with advanced soft tissue sarcoma, after failure of anthracyclines and ifosfamide, or who are unsuited to receive these agents and in combination with pegylated liposomal doxorubicin (PLD) for the treatment of patients with relapsed platinum-sensitive ovarian cancer. We present a case of a 76-year-old patient with progressive metastatic lung lesions from a previously resected primary leiomyosarcoma of the thigh and moderate renal failure, who achieved 17 months of disease stability during third-line treatment with trabectedin. Trabectedin was not associated with any cumulative toxicity and was consistently well tolerated for a total of 22 treatment cycles. Current evidence on trabectedin is also presented.

Increasing the chances for platinum-sensitive ovarian cancer patients.

Ovarian carcinoma is still one of the most common causes of death from cancer in the western world. Despite high sensitivity to chemotherapy, the majority of patients will relapse within 3 years. In this article the focus is centered on patients who have a late relapse (>12 months). Carboplatin-based regimens are the backbone of treatment for this group, producing clinical benefit with higher rates for progression-free and overall survival. However, not all patients can continue with platinum owing to loss of activity or toxicity (hypersensitivity, neurotoxicity and ototoxicity). In particular, hypersensitivity reactions to carboplatin are a concern and have been reported in approximately 15-20% of women receiving the drug. When expectations for a positive outcome with carboplatin are good, desensitization protocols may be useful so as to continue treatment. If platinum-based regimens are not possible then alternative forms of treatment are required; additional research efforts are being directed towards the development of nonplatinum-based therapies. Promising results have been obtained with the combination of trabectedin plus pegylated liposomal doxorubicin, providing encouragement that it will be a viable option for patients with recurrent ovarian cancer who cannot be treated with a platinum-based chemotherapeutic option.

Efficacy of trabectedin in patients with advanced or metastatic alveolar soft-part sarcoma.

BACKGROUND: Alveolar soft-part sarcoma (ASPS) is a rare sarcoma often occurring in young patients that is characterized by the unbalanced translocation der(17)t(X;17) (p11;q25). Although it usually shows an indolent clinical course, the prognosis is usually poor in advanced disease. Since standard chemotherapy regimens used in soft-tissue sarcomas lack efficacy in ASPS, new therapeutic options are needed. We investigated the efficacy of trabectedin, which has demonstrated activity in a variety of cancer types including some of the most prevalent translocation-related sarcomas. PATIENTS AND METHODS: 7 patients with metastatic or advanced ASPS treated with trabectedin in the Sarcoma Center Berlin-Brandenburg and the University Hospital of Greifswald were analyzed for median progression-free survival (mPFS), overall survival (OS), and therapy-related toxicity. RESULTS: In 6 patients with documented disease progression, disease stabilization was reached with trabectedin; only 1 patient experienced progressive disease. The mPFS and OS were 7 months and 21 months, respectively, since the start of trabectedin treatment. Overall, no severe Common Toxicity Criteria (CTC) grade 3 or 4 toxicity was observed. CONCLUSIONS: The poor prognosis of patients with ASPS has so far been due to the unavailability of effective systemic treatments. Trabectedin can be considered the only currently registered drug with clinical activity in this disease.

Trabectedin plus pegylated liposomal doxorubicin in relapsed ovarian cancer delays third-line chemotherapy and prolongs the platinum-free interval.

BACKGROUND: OVA-301 is a large randomized trial that showed superiority of trabectedin plus pegylated liposomal doxorubicin (PLD; CentoCor Ortho Biotech Products L.P., Raritan, NJ, USA). over single-agent PLD in 672 patients with relapsed ovarian cancer, particularly in the partially platinum-sensitive subgroup [platinum-free interval (PFI) of 6-12 months]. This superiority has been suggested to be due to the differential impact of subsequent (platinum) therapy. PATIENTS AND METHODS: a detailed analysis of subsequent therapies and survival outcomes in the overall population and in the subsets according to platinum sensitivity was therefore conducted. RESULTS: similar proportions of patients received subsequent therapy in each arm (76% versus 77%), including further platinum-based regimens (49% versus 55%). Patients in the trabectedin/PLD arm received subsequent chemotherapy at a later time (median delay 2.5 months versus PLD arm). Overall survival from subsequent platinum was significantly prolonged in the partially platinum-sensitive disease subset (hazard ratio = 0.63; P = 0.0357). CONCLUSION: the superiority of trabectedin/PLD over single-agent PLD in OVA-301 cannot be explained by differences in the extent or nature of subsequent therapies administered to these patients. On the other hand, these exploratory analyses support the hypothesis that the enhanced survival benefits in the partially platinum-sensitive subset might be due to an extended PFI leading to longer survival with subsequent platinum.

Response to trabectedin treatment in a highly pretreated patient with an advanced meningeal hemangiopericytoma.

Meningeal hemangiopericytoma is an uncommon and aggressive malignancy that, in contrast to meningiomas, shows a high propensity for local recurrence and the development of late extraneural metastases. The results of chemotherapy in advanced hemangiopericytoma have been disappointing, and they have been particularly poor in cases located in the meninges. We report a case of a heavily pretreated metastatic meningeal hemangiopericytoma in which fourth-line chemotherapy with trabectedin, a marine-derived antineoplastic agent effective in treating advanced soft tissue sarcomas, resulted in clinical benefit.

Management of relapsed ovarian cancer in routine clinical practice: a case study.

OBJECTIVE: In patients with recurrent ovarian cancer, there are certain situations where further surgery and/or next-line platinum-based chemotherapy is not feasible or is not the best option. Multidisciplinary teams have a key role in reviewing available options and selecting the most appropriate intervention. METHODS: A case study of relapsed ovarian cancer illustrates some of the factors that shape decision-making and shows the potential of a non-platinum-based regimen in the context of limited platinum sensitivity. RESULTS: Taking into account the patient's individual circumstances, many options were discarded by the tumor board. Further surgery was not recommended as initial surgery had been suboptimal. Platinum-based regimens incorporating bevacizumab were not indicated due to exposure to bevacizumab in the first-line setting. Other platinum-based regimens were not recommended in general, due to limited platinum sensitivity (relapse <12 months after previous platinum) and unacceptable toxicity. A decision was taken to treat with trabectedin + pegylated liposomal doxorubicin (PLD), which provided 15 months of disease control. Subsequent platinum rechallenge led to a complete response. CONCLUSION: Second-line use of trabectedin + PLD in patients with limited platinum sensitivity may restore sensitivity at next platinum.

Trabectedin for women with ovarian carcinoma after treatment with platinum and taxanes fails.

PURPOSE: To assess the efficacy and toxicity of the marine-derived alkaloid trabectedin (ET-743) in patients with advanced ovarian cancer refractory to or experiencing disease relapse after platinum- and taxane-based chemotherapy. PATIENTS AND METHODS: Fifty-nine patients from four institutions either resistant (n = 30) or sensitive (n = 29) to prior platinum and taxanes were treated with a 3-hour infusion of trabectedin every 3 weeks. Patients were monitored weekly for toxicity and restaged every two cycles for response. Response was assessed according to Response Evaluation Criteria in Solid Tumors Group. RESULTS: The peer-reviewed objective response rate in platinum-sensitive patients was 43% (95% CI, 23% to 65%) with an estimated median time to progression of 7.9 months (95% CI, 7.5 to 14.1 months); in platinum-resistant patients two partial responses were observed. Responses were durable for up to 12.9 months (median, 5 months). The predominant toxicities at the recommended dose of 1,300 microg/m(2) were neutropenia, asthenia, and self-limited increase of aminotransferases never requiring treatment interruption. CONCLUSION: Trabectedin administered as a 3-hour infusion at 1,300 microg/m(2) is a safe new drug with promising activity in relapsed ovarian cancer, showing a 43% objective response rate in patients with platinum-sensitive disease, which favorably compares with other salvage treatments and warrants additional development either alone or in combination.

Factors to consider and questions to ask in the management of recurrent ovarian cancer: a focus on the role of trabectedin + pegylated liposomal doxorubicin.

INTRODUCTION: Given the heterogeneity of both disease and clinical situation, recurrent ovarian cancer continues to be a considerable therapeutic challenge. While newer treatment options have led to improved clinical outcomes, treatment selection has become more complex. An increasing number of clinical questions must be addressed before the optimal strategy and sequence can be decided for an individual patient. Areas covered: In this review, evidence is examined to guide decision-making for the main treatment options of surgery, chemotherapy and targeted therapy. Expert commentary: For each option, the same set of patient- and tumor-related factors can be used to identify appropriate candidates. Over the next few years, results of ongoing randomized studies are expected to shed light on several unresolved issues in the treatment of recurrent ovarian cancer.

The association between body composition and toxicities from the combination of Doxil and trabectedin in patients with advanced relapsed ovarian cancer.

Emerging research suggests that body composition can predict toxicity of certain chemotherapeutic agents. We used data from a clinical study to investigate associations between body composition and combined DOXIL (pegylated liposomal doxorubicin; PLD) and trabectedin (Yondelis) treatment, an effective treatment for ovarian cancer that shows high interpatient variation in toxicity profile. Patients (n = 74) participating in a phase III randomized trial of relapsed advanced ovarian cancer receiving PLD (30 mg/m(2)) and trabectedin (1.1 mg/m(2)) were included. Muscle tissue was measured by analysis of computerized tomography images, and an extrapolation of muscle and adipose tissue to lean body mass (LBM) and fat mass (FM) were employed. Toxicity profile after cycle 1 was used and graded according to the National Cancer Institute Common Toxicity Criteria (version 3). Patients presented with a wide range of body composition. In overweight and obese patients (body mass index (BMI) ≥ 25 kg/m(2), n = 48) toxicity was more prevalent in those with lower BMI (p = 0.028) and a lower FM (n = 43, p = 0.034). Although LBM alone was not predictive of toxicity, a lower FM/LBM ratio was the most powerful variable associated with toxicity (p = 0.006). A different pattern emerged among normal weight patients (n = 26) where toxicity was rare among patients with smaller BMI (<21 kg/m(2)). A clear association between both FM and LBM (primarily driven by FM) in explaining PLD plus trabectedin toxicity emerged, but only in individuals with excess body weight, with a lower ratio predicting higher exposure and risk for toxicity.

Prolonged disease stability with trabectedin in two monorenal patients with retroperitoneal sarcoma.

Soft tissue sarcomas constitute a heterogeneous group of tumors of mesenchymal origin: at present, more than 50 separate histological subtypes of soft tissue sarcoma have been listed. Although there have been advances in the understanding of these tumors and their treatment over the past few years, there is still a lack of consensus on the standard of care, and new therapeutic options are eagerly awaited. Trabectedin has been approved for the treatment of patients with advanced soft tissue sarcomas after failure of anthracyclines and ifosfamide. However, the effectiveness and tolerability of this agent in retroperitoneal soft tissue sarcomas have been poorly characterized. Here we report the cases of two monorenal patients with a retroperitoneal sarcoma who achieved prolonged stabilization of disease with trabectedin. Trabectedin-associated toxicities were generally mild and were successfully managed by supportive care. Of note, the patients did not experience clinically relevant myelosuppression, which is currently considered the limiting toxicity of trabectedin.