pazopanib has been researched along with Leiomyosarcoma* in 19 studies
3 review(s) available for pazopanib and Leiomyosarcoma
Article | Year |
---|---|
Current state of the art and emerging pharmacotherapy for uterine leiomyosarcomas.
Uterine leiomyosarcomas (ULMS) account for 1% of all uterine malignancies and for 30% of all uterine sarcomas. The preoperative diagnosis of ULMS is challenging for the physicians, as the symptoms of these tumors are often vague and nonspecific. Moreover, as ULMS have an aggressive biologic behavior, affected women frequently have very poor prognosis.. The aim of this review is to describe the current pharmacotherapy for ULMS, including the ongoing clinical trials.. Surgery is the standard treatment for patients with early-stage ULMS. In this setting, the role of adjuvant therapies is still unclear. In the case of advanced, persistent, or recurrent ULMS, chemotherapy is the standard care with the most frequently used drug being doxorubicin. As the outcomes for patients with the currently available conventional single or combined regimens are far from being satisfactory, new alternative and innovative medical compounds have or are being evaluated. Recently, pazopanib, and olaratumab, two innovative targeted drugs, have been approved by the Food and Drug Administration (FDA) for treating advanced soft-tissue sarcoma, including ULMS. However, further clinical investigations into new and innovation therapeutic options are warranted. Topics: Antibodies, Monoclonal; Antineoplastic Agents; Combined Modality Therapy; Doxorubicin; Female; Humans; Indazoles; Leiomyosarcoma; Prognosis; Pyrimidines; Sulfonamides; Uterine Neoplasms | 2019 |
Pharmacokinetic drug evaluation of pazopanib for the treatment of uterine leiomyosarcomas.
Uterine leiomyosarcomas (ULMS) represent 1.3% of all uterine malignant tumors. Surgery is the curative treatment for patients with early stage disease. In case of advanced, persistent or recurrent tumor, chemotherapy represents the standard of care, but these patients have a poor prognosis. As the results with available therapies are far from being satisfactory, research is focusing on identification of new compounds. In 2012 the Food and Drug Administration (FDA) licensed pazopanib for the treatment of advanced soft-tissue sarcomas failing previous chemotherapy. Areas covered: The aim of this article is to review the literature on the pharmacokinetics, pharmacodynamics, clinical efficacy and safety of the tyrosine kinase inhibitor (TKI), pazopanib in the treatment of ULMS. Expert opinion: The discovery of some relevant signalling pathways in LMS cells led to the development of new targeted drugs with promising results in the management of these tumors. Pazopanib is a multi-target second-generation TKI with activity against growth factors involved in angiogenesis. It has shown promising results both in terms of efficacy and safety, as shown in the EORTC 62043 Study and the PALETTE trial. Further studies are awaited to evaluate its efficacy in uterine leiomyosarcomas. Topics: Angiogenesis Inhibitors; Female; Humans; Indazoles; Leiomyosarcoma; Protein Kinase Inhibitors; Pyrimidines; Sulfonamides; Uterine Neoplasms | 2017 |
Uterine leiomyosarcoma: Epidemiology, contemporary treatment strategies and the impact of uterine morcellation.
Leiomyosarcoma, a rare tumor subtype, accounts for 1% of all uterine malignancies, but contributes to a significant proportion of uterine cancer deaths. Surgery is considered the mainstay of treatment for all soft tissue sarcomas, including uterine variants. However, uterine leiomyosarcoma is challenging to diagnose preoperatively and can mimic the appearance of benign uterine leiomyomas. Recently, concerns have grown in this regard, as surgeons have utilized uterine morcellation and myomectomy procedures unknowingly in the setting of occult uterine sarcoma. Because of aggressive tumor biology and relative chemotherapy and radiotherapy resistance, efficacious therapies to achieve prolonged survival or cure in those with both early and advanced-stage uterine leiomyosarcoma have been elusive. The strongest determinant of survival remains stage at diagnosis, though prediction models may provide a more accurate prognosis. Given the aggressive nature of this sarcoma subtype, novel early detection strategies and targeted therapies are the focus of several recently published and ongoing studies. While gemcitabine/docetaxel and doxorubicin remain the most active regimens in the treatment of advanced or recurrent disease, currently available cytotoxic regimens remain inadequate, with 5-year disease-specific survival of <30%. Pazopanib, trabectedin and olaratumab, are FDA-approved, targeted therapies with activity in uterine and other leiomyosarcomas, while aromatase inhibitors and immunotherapies are under active investigation. This review provides a critical appraisal of the literature regarding the contemporary surgical and medical management of uterine leiomyosarcoma, the role of targeted therapies, and the implications of uterine morcellation on gynecologic surgical practice. Topics: Angiogenesis Inhibitors; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Aromatase Inhibitors; Chemotherapy, Adjuvant; Deoxycytidine; Diagnostic Errors; Dioxoles; Docetaxel; Doxorubicin; Female; Gemcitabine; Humans; Hysterectomy; Indazoles; Laparoscopy; Leiomyoma; Leiomyosarcoma; Morcellation; Neoplasm Staging; Pyrimidines; Sulfonamides; Taxoids; Tetrahydroisoquinolines; Trabectedin; Uterine Myomectomy; Uterine Neoplasms | 2017 |
2 trial(s) available for pazopanib and Leiomyosarcoma
Article | Year |
---|---|
A phase II of gemcitabine combined with pazopanib followed by pazopanib maintenance, as second-line treatment in patients with advanced leiomyosarcomas: A unicancer French Sarcoma Group study (LMS03 study).
Options in second-line therapy after doxorubicin-based chemotherapy for metastatic/advanced leiomyosarcoma include gemcitabine (G), trabectedin and pazopanib (P) monotherapy. Currently, no combination therapy is better than monotherapy. LMS03 is an open-label multicentre single-group phase II study designed to assess the efficacy and tolerance of G + P in the second-line setting.. 106 pts were included with a mean age of 59.8 years and an ECOG 0 in 63.5%; the primary tumour site was uterus in 61%. Pts were treated with P + G for a median of 3.8 mo, and P for a median of 4.2 mo. The 9-month PFS rate was 32.1% (95% CI 23.1-41.1). After a median follow-up of 14.2 months, the PFS was 6.5 months (95% CI 5.6-8.2), and the overall survival was 22.4 months (95% CI 16.9-26.5). The best response was 23.8%. The most frequent reported grade 3-4 adverse events were haematological.. LMS03 failed to show that second-line therapy, with gemcitabine combined with pazopanib, followed by pazopanib alone, was beneficial for advanced LMS patients. Eudract N°2011-001308-36 and NCT01442662. Topics: Adult; Aged; Aged, 80 and over; Antimetabolites, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Deoxycytidine; Female; Gemcitabine; Humans; Indazoles; Leiomyosarcoma; Male; Middle Aged; Pyrimidines; Sulfonamides | 2020 |
Outcome of uterine sarcoma patients treated with pazopanib: A retrospective analysis based on two European Organisation for Research and Treatment of Cancer (EORTC) Soft Tissue and Bone Sarcoma Group (STBSG) clinical trials 62043 and 62072.
Uterine sarcomas are a group of mesenchymal tumours comprising several histologies. They have a high recurrence rate following surgery, modest outcome to systemic therapy, and poor overall survival. Pazopanib is a multi-targeted tyrosine kinase inhibitor approved for non-adipocytic advanced soft tissue sarcomas (STS). Here we investigated whether response to pazopanib in patients with uterine sarcomas differs from that of patients with non-uterine sarcomas.. Uterine sarcoma patients were retrieved from all soft tissue sarcoma patients treated with pazopanib in EORTC Phase II (n=10) and Phase III (PALETTE) (n=34) studies. Patient and tumour characteristics, response, progression free and overall survival data were compared.. Forty-four patients with uterine sarcoma were treated with pazopanib. The majority of patients had uterine leiomyosarcoma (LMS) (n=39, 88.6%) with high grade tumours (n=37, 84.1%) compared to 54.8% (n=164) in the non-uterine population. The median age was 55years (range 33-79) and median follow up was 2.3years. Uterine patients were heavily pre-treated, 61.3% having ≥2 lines of chemotherapy prior to pazopanib compared to 40.8% in the non-uterine population. Five patients (11%), all LMS, had a partial response (95% CI 3.8-24.6). Median progression free survival (PFS) 3.0months (95% CI 2.5-4.7) in uterine versus 4.5 (95% CI 3.7-5.1) in non-uterine STS. Median overall survival (OS) was 17.5months (95% CI 11.1-19.6), longer than the non-uterine population, 11.1months (95% CI 10.2-12.0) (p=0.352).. Despite heavy pre-treatment, pazopanib shows signs of activity in patients with uterine sarcoma with the similar outcomes to patients with non-uterine STS. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Female; Humans; Indazoles; Leiomyosarcoma; Middle Aged; Prognosis; Protein Kinase Inhibitors; Pyrimidines; Retrospective Studies; Sarcoma; Sulfonamides; Survival Rate; Uterine Neoplasms; Young Adult | 2016 |
14 other study(ies) available for pazopanib and Leiomyosarcoma
Article | Year |
---|---|
Real-world outcomes of pazopanib in metastatic soft tissue sarcoma: a retrospective Turkish oncology group (TOG) study.
Description of patient characteristics, effectiveness and safety in Turkish patients treated with pazopanib for metastatic soft tissue sarcoma (STS).. This multicenter study is based on retrospective review of hospital medical records of patients (≥ 18 years) treated with pazopanib for non-adipocytic metastatic STS at 37 Oncology clinics across Turkey. Objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS) and overall survival (OS) were evaluated with further analysis of data on the three most common histological subtypes (leiomyosarcoma [LMS], undifferentiated pleomorphic sarcoma [UPS], synovial sarcoma [SS]) in the cohort.. Data of 552 adults (57.6% women, median age: 52 years) were analyzed. DCR and ORR were 43.1% and 30.8%, respectively. Median PFS was 6.7 months and OS was 13.8 months. For LMS, UPS and SS, median PFSs were 6.1, 5.9 and 7.53 months and median OSs were 15.03, 12.87 and 12.27 months, respectively. ECOG ≥ 2 was associated with poor PFS and OS. Liver metastasis was only a factor for progression. Second-line use of pazopanib (vs. front-line) was associated with better PFS, its use beyond third line predicted worse OS. Adverse events (AE) occurred in 82.7% of patients. Most common AEs were fatigue (58.3%) and anorexia (52.3%) which were graded as ≥ 3 in 8.2% and 7.4% of patients, respectively.. Pazopanib is effective and well-tolerated in treatment of non-adipocytic metastatic STS. Its earlier use (at second-line), good performance status may result in better outcomes. Worldwide scientific collaborations are important to gain knowledge on rarer STS subtypes by conducting studies in larger patient populations. Topics: Adult; Female; Humans; Indazoles; Leiomyosarcoma; Male; Middle Aged; Neoplasms, Second Primary; Retrospective Studies; Sarcoma; Sarcoma, Synovial; Soft Tissue Neoplasms; Turkey | 2023 |
Pazopanib for metastatic soft-tissue sarcoma: A multicenter retrospective study.
Soft tissue sarcomas are associated with a poor prognosis and low chemotherapeutic efficiency. Pazopanib is an orally available multi-tyrosine kinase inhibitor that was explored in patients with non-adipocytic advanced soft tissue sarcomas. The aim of this retrospective study was to evaluate the real life data of single-agent pazopanib efficacy and safety for soft tissue sarcomas in the Turkish population.. We evaluated a total of 103 patients (41 males, 62 females) who received pazopanib for advanced non-adipocytic soft tissue sarcomas diagnosis in eight centers of Turkey, retrospectively. The pazopanib dose was 800 mg once daily. Progression-free survival, overall survival, and adverse events were analyzed.. The median age was 50 years (range, 38-58). Majority of the patients had leimyosarcoma (41%). Median progression-free survival was 4.3 months, and the median overall survival was 10.1 months. The main common toxicities were fatigue, anorexia, weight loss, nausea, hypertension, and grade ≥3 toxicities were fatigue, anorexia, weight loss, and liver disorder.. Pazopanib is an efficient and tolerable agent and is well tolerated in good performance status patients with relapsed, advanced non-adipocytic soft tissue sarcomas. Topics: Adult; Female; Humans; Indazoles; Leiomyosarcoma; Male; Middle Aged; Progression-Free Survival; Protein Kinase Inhibitors; Pyrimidines; Retrospective Studies; Sarcoma; Soft Tissue Neoplasms; Sulfonamides; Survival Analysis | 2021 |
Synergistic effects of pazopanib and hyperthermia against uterine leiomyosarcoma growth mediated by downregulation of histone acetyltransferase 1.
Pazopanib-a multitargeted tyrosine kinase inhibitor with prominent antiangiogenic effects-has shown promise in the treatment of soft-tissue sarcomas. Hyperthermia has been also applied as an adjunctive treatment to chemotherapy for these malignancies. Here, we show that pazopanib and hyperthermia act synergistically in inhibiting uterine leiomyosarcoma (LMS) cell growth. Compared with either treatment alone, the combination of pazopanib and hyperthermia exerted the highest antitumor activity in a xenograft model. Mechanistically, we found that combined treatment with pazopanib and hyperthermia inhibited histone acetyltransferase 1 (HAT1) expression in LMS cells. The Clock element on the HAT1 promoter was critical for pazopanib- and hyperthermia-induced HAT1 downregulation. Inhibition of HAT1-either by pazopanib and hyperthermia or through HAT1 silencing-was mediated by suppression of Clock. Accordingly, Clock protein reconstitution rescued both HAT1 levels and HAT1-mediated histone acetylation. Immunohistochemistry revealed a higher expression of HAT1 in uterine LMS than in leiomyomas (p = 0.007), with high HAT1 expression levels being associated with poor clinical outcomes (p = 0.007). We conclude that pazopanib and hyperthermia exert synergistic effects against LMS growth by inhibiting HAT1. Further preclinical studies on HAT1 as a potential drug target in uterine LMS are warranted, especially in combination with hyperthermia. KEY MESSAGES: Pazopanib and hyperthermia inhibit the growth of leiomyosarcoma. Their combined use inhibits HAT1 expression in leiomyosarcoma cells. The promoter Clock element is required for HAT1 downregulation. HAT1 expression is higher in leiomyosarcoma than in leiomyomas. An increased HAT1 expression is associated with poor clinical outcomes. Topics: Angiogenesis Inhibitors; Antineoplastic Agents; Biomarkers; CLOCK Proteins; Female; Gene Expression Regulation, Neoplastic; Histone Acetyltransferases; Humans; Hyperthermia, Induced; Indazoles; Leiomyosarcoma; Pyrimidines; Sulfonamides; Uterine Neoplasms | 2020 |
Tumour-bowel fistula as a possible complication of pazopanib therapy in retroperitoneal leiomyosarcoma.
Pazopanib is a vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) that inhibits the vascular endothelial growth factor receptor A pathway and has the potential to cause ischaemic bowel changes, including perforation. Here we report a case of a 51-year-old man with large, metastatic, retroperitoneal leiomyosarcoma that developed a tumour-bowel fistula after 4 weeks of pazopanib therapy. He presented to the emergency department with sepsis and 1-week history of worsening fever, chills, nausea and diarrhoea. Abdominal CT findings of mesenteric and portal vein gas, commonly found in mesenteric ischaemia and VEGFR modulator-induced bowel toxicity, provided evidence for the causal relation. Unfortunately, the case was not amenable to surgery and patient succumbed to the illness. Topics: Angiogenesis Inhibitors; Diagnosis, Differential; Humans; Indazoles; Intestinal Fistula; Intestinal Perforation; Leiomyosarcoma; Male; Middle Aged; Pyrimidines; Retroperitoneal Neoplasms; Sulfonamides; Tomography, X-Ray Computed | 2019 |
Promising effects of pazopanib with radiation on an advanced prostate leiomyosarcoma after failure of systemic chemotherapy.
Topics: Antineoplastic Agents; Combined Modality Therapy; Gamma Rays; Humans; Indazoles; Leiomyosarcoma; Male; Middle Aged; Prostate; Prostatic Neoplasms; Pyrimidines; Sulfonamides; Tomography, X-Ray Computed; Treatment Outcome | 2019 |
Cardiotoxicity Monitoring in Patients Treated with Tyrosine Kinase Inhibitors.
Tyrosine kinase inhibitors (TKIs) can cause cardiotoxicity, and some suggest routine monitoring of cardiac function during TKI use. We describe two cases of TKI-induced heart failure (HF) that suggest the utility of monitoring with laboratory tests is questionable. One patient developed HF 5 days after starting pazopanib. The other developed HF while receiving 25 mg per day sunitinib, and had previously received a higher dose (50 mg per day) with no symptoms of cardiotoxicy. In addition, she later received 5 cycles of sunitinib (25 mg per day) without developing an abnormal left ventricular ejection fraction (LVEF) value by echocardiography or cardiac symptoms. Although the LVEF is commonly performed to monitor TKI cardiotoxicity, evidence for its predictive utility is limited. These cases raise questions regarding the practical utility of sequential measurement of LVEF in adults treated with TKIs. We suggest a simple daily activity such as stair climbing to monitor exercise tolerance. Topics: Aged; Carcinoma, Renal Cell; Female; Heart Failure; Humans; Indazoles; Kidney Neoplasms; Leiomyosarcoma; Middle Aged; Prognosis; Protein Kinase Inhibitors; Pyrimidines; Sulfonamides; Sunitinib | 2019 |
A Case Report of Metastatic Primary Thyroid Leiomyosarcoma Treated with Pazopanib.
Topics: Aged; Antineoplastic Agents; Female; Humans; Indazoles; Leiomyosarcoma; Neoplasm Metastasis; Pyrimidines; Sulfonamides; Thyroid Neoplasms | 2018 |
Harnessing soft tissue sarcoma with low-dose pazopanib - a matter of blood levels.
Pazopanib is a tyrosine kinase inhibitor indicated for the treatment of renal cell carcinoma and soft tissue sarcoma. Despite the high inter-patient variability in pharmacokinetic exposure, pazopanib is administered at a fixed dose of 800 mg once daily (QD). Pharmacokinetic exposure is linked to both efficacy and toxicity. In this case report, we illustrate the value of therapeutic drug monitoring by describing two patients with adequate pazopanib trough concentrations (C. Patient A is a 69-year-old woman with metastatic leiomyosarcoma who had significant toxicities and a high C. It could be valuable to measure pazopanib levels in case of dose reductions due to toxicity, as exposure could still be adequate at considerably lower than standard doses. Topics: Aged; Angiogenesis Inhibitors; Dose-Response Relationship, Drug; Female; Humans; Indazoles; Leiomyosarcoma; Male; Middle Aged; Protein Kinase Inhibitors; Pyrimidines; Soft Tissue Neoplasms; Sulfonamides | 2018 |
Positive response of a primary leiomyosarcoma of the breast following salvage hyperthermia and pazopanib.
Topics: Breast Neoplasms; Female; Humans; Hyperthermia, Induced; Indazoles; Leiomyosarcoma; Middle Aged; Pyrimidines; Sulfonamides | 2018 |
Treatment patterns and clinical outcomes with pazopanib in patients with advanced soft tissue sarcomas in a compassionate use setting: results of the SPIRE study
A named patient program (NPP) was designed to provide patients with advanced soft-tissue sarcoma (aSTS) access to pazopanib, a multitargeted tyrosine kinase inhibitor. The SPIRE study was a retrospective chart review of participating patients.. Eligibility criteria for the NPP and SPIRE mirrored those of the pivotal phase-III study, PALETTE, which compared pazopanib with placebo in patients ≥18 years with aSTS and whose disease had progressed during or following prior chemotherapy or were otherwise unsuitable for chemotherapy. Outcomes of interest included treatment patterns, treatment duration, relative dose intensity, progression-free survival (PFS), overall survival (OS), clinical benefit rate, adverse events (AEs) and reasons for treatment discontinuation.. A total of 211 patients were enrolled (median age 56 years; 60% female). Most patients received pazopanib in second- and third-line therapy (28.0% and 28.4%, respectively), followed by fourth line (19.0%) and ≥ fifth line (18.5%). The median duration of pazopanib treatment was 3.1 months (95% CI: 2.8-3.8), with a mean daily dose of 715 mg equating to 92% of recommended dose. Median OS was 11.1 months and clinical benefit rate was 46%. There was evidence of some clinical benefit across most histological subtypes. At study end, 40% of patients were alive and of these, 18% remained on pazopanib. Thirteen percent (13%) of patients discontinued pazopanib due to AEs.. The SPIRE study demonstrated activity of pazopanib in heavily pretreated aSTS patients in a compassionate use setting. No new safety concerns were noted. Reassuringly, the relative dose intensity of pazopanib was 92%. Topics: Angiogenesis Inhibitors; Compassionate Use Trials; Disease-Free Survival; Female; Hemangiosarcoma; Humans; Indazoles; Leiomyosarcoma; Lung Neoplasms; Male; Middle Aged; Pyrimidines; Retrospective Studies; Sarcoma; Sarcoma, Synovial; Solitary Fibrous Tumors; Sulfonamides; Survival Rate; Time Factors; Uterine Neoplasms | 2017 |
The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study.
Because the efficacy and safety of pazopanib in Japanese patients with soft tissue sarcoma (STS) had not been evaluated previously in a large-scale cohort, the authors investigated the efficacy and safety of pazopanib in 156 Japanese patients with relapsed STS. This was a retrospective study based on the collection of real-life, postmarketing surveillance data.. Patients received pazopanib with the objective of treating local recurrence (n = 20), metastasis (n = 104), and both (n = 32). The patient median age was 53.8 years. The primary objective of this study was to clarify the efficacy of pazopanib for patients with STS.. The median treatment duration was 28.7 weeks, and the average dose intensity of pazopanib was 609 mg. Adverse events occurred in 127 patients (81.4%). In addition to the main common toxicities, such as hypertension and liver disorder, pneumothorax (n = 11) and thrombocytopenia (n = 16) also were observed. The median progression-free survival for all patients was 15.4 weeks. The median progression-free survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 18.6 weeks, 16.4 weeks, 15.3 weeks, and 8 weeks, respectively. The median survival for all patients was 11.2 months. The median survival for patients with leiomyosarcoma, synovial sarcoma, undifferentiated pleomorphic sarcoma, and liposarcoma was 20.1 months, 10.6 months, 9.5 months, and 7.3 months, respectively.. There were apparent differences in the efficacy of pazopanib treatment among histologic types of STS. Pazopanib treatment is a new treatment option; however, adverse events like pneumothorax and thrombocytopenia, which did not occur frequently in the PALETTE study (pazopanib for metastatic soft-tissue sarcoma), should be taken into consideration. Cancer 2016;122:1408-16. © 2016 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. Topics: Adolescent; Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Chemical and Drug Induced Liver Injury; Disease-Free Survival; Female; Fibrosarcoma; Humans; Hypertension; Indazoles; Japan; Leiomyosarcoma; Liposarcoma; Male; Middle Aged; Neoplasm Recurrence, Local; Neurilemmoma; Pneumothorax; Product Surveillance, Postmarketing; Pyrimidines; Retrospective Studies; Sarcoma; Sarcoma, Synovial; Sulfonamides; Survival Analysis; Thrombocytopenia | 2016 |
Autopsy case of pulmonary artery sarcoma forming aneurysm without FDG uptake.
Topics: Adult; Aneurysm; Aneurysm, Ruptured; Fatal Outcome; Fluorine Radioisotopes; Fluorodeoxyglucose F18; Humans; Indazoles; Leiomyosarcoma; Lung; Male; Neoplasm Invasiveness; Positron-Emission Tomography; Pulmonary Artery; Pyrimidines; Radiopharmaceuticals; Rupture, Spontaneous; Shock, Hemorrhagic; Sulfonamides; Vascular Neoplasms | 2016 |
[A Case of Severe Hematological Toxicity in Response to Pazopanib].
The patient(woman, approximately 46 years old)began pazopanib (PAZ) treatment (800 mg/day)f ollowing the recurrence of retroperitoneal leiomyosarcoma. Prior to treatment, the patient's platelet count was 18.6×10(4)/µl and her neutrophil count was 1.61×10(3)/µl . The platelet count decreased to 9.2×10(4)/µl on day 7 and to 5.4×10(4)/µl on day 21 after commencement of treatment. The neutrophil count was 0.97×10(3)/µl on day 28 and 0.68×10(3)/µl on day 35 after commencement of treatment. Thus, PAZ treatment was stopped on day 35. The blood sampling results on day 42 after commencement of treatment showed that the platelet count was 13.0×10(4)/µl and that the neutrophil count had recovered to 1.28×10(3)/µl . At that time, PAZ treatment was resumed at a reduced dose of 600 mg/day. By day 84 after commencement of treatment, the platelet count had increased from 12.7 to 13.8×10(4)/µl and the neutrophil count had increased from 1.02 to 1.34×10(3)/µl ; treatment was subsequently continued. The main adverse effects that have been reported for PAZ are hypertension and frequent liver dysfunction; these reports also indicate that the incidence of severe cytopenia(thrombocytopenia, neutropenia)is quite low. However, our patient exhibited cytopenia after commencement of PAZ treatment and her blood cell counts recovered once treatment was ceased, independent of other possible medications. Our findings suggest that cytopenia should be considered as an adverse effect of PAZ. Topics: Angiogenesis Inducing Agents; Female; Humans; Indazoles; Leiomyosarcoma; Middle Aged; Neutropenia; Pyrimidines; Recurrence; Retroperitoneal Neoplasms; Sulfonamides; Thrombocytopenia | 2016 |
A Case of Uterine Leiomyosarcoma with Long-Term Disease Control by Pazopanib.
Uterine leiomyosarcoma (ULMS) is an aggressive tumor associated with high rates of progression, recurrence, and mortality. Pazopanib is the only approved molecular targeted drug for advanced soft tissue sarcoma, and it has been proven to prolong progression-free survival relative to placebo. We herein report a case of ULMS with multiple lung metastases treated with pazopanib, which led to sustained disease control for 44 weeks. A 53-year-old woman was referred to our hospital due to massive uterine bleeding from a uterine corpus tumor mass. Total abdominal hysterectomy with bilateral salpingo-oophorectomy was performed as emergency surgery. The final histopathological diagnosis was uterine leiomyosarcoma, and computed tomography revealed multiple lung metastases. After chemotherapy with 17 cycles of gemcitabine and docetaxel and two cycles of doxorubicin, the lung metastases had increased in size and new lesions had appeared. Pazopanib administration at 800 mg/day was started as third-line therapy. Ten weeks later, the dose of pazopanib was reduced to 600 mg/day because of hepatic impairment and hypertension. However, lung metastases of ULMS were stabilized by pazopanib administration for about 44 weeks without a decline in the patient's quality of life. After 44 weeks of therapy, pazopanib administration was discontinued because of progressive disease and worsening of the patient's respiratory status. Pazopanib is an oral multityrosine kinase inhibitor of vascular endothelial growth factor receptor-1, -2, and -3; platelet-derived growth factor-α and -β; and c-Kit receptor. The role of pazopanib may be clinically significant in the treatment of advanced ULMS. Topics: Antineoplastic Agents; Female; Humans; Indazoles; Leiomyosarcoma; Lung Neoplasms; Middle Aged; Protein Kinase Inhibitors; Pyrimidines; Salvage Therapy; Sulfonamides; Tomography, X-Ray Computed; Uterine Neoplasms | 2016 |