pazopanib and Hemangiosarcoma

Cardiac angiosarcoma (AS) is an extremely rare, malignant vascular tumor with <10 cases reported in the pediatric literature. Prognosis is dismal with overall survival often <1 year from initial diagnosis. In this report, we present the case of a 10-year-old boy with metastatic cardiac AS who is currently alive and is the longest pediatric survivor of metastatic cardiac AS reported in the literature. This is the only published pediatric case to successfully use a combination of surgical resection, conventional chemotherapy, radiation and targeted therapies including bevacizumab and pazopanib for metastatic cardiac AS.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Chemoradiotherapy; Child; Combined Modality Therapy; Heart Neoplasms; Hemangiosarcoma; Humans; Indazoles; Male; Neoplasms, Second Primary; Prognosis; Pyrimidines; Sulfonamides; Surgical Procedures, Operative

Angiosarcoma is a rare sarcoma subtype with a poor outcome. Carotuximab plus pazopanib produced a median progression-free survival (PFS) of 7.8 months in pazopanib-naive patients with chemotherapy-refractory angiosarcoma in a phase 1/2 trial.. To determine whether carotuximab plus pazopanib improves PFS compared with pazopanib alone in patients with advanced angiosarcoma.. The TAPPAS Trial: An Adaptive Enrichment Phase 3 Trial of TRC105 and Pazopanib vs Pazopanib Alone in Patients With Advanced Angiosarcoma was a multinational, multicenter, open-label, parallel-group, phase 3 randomized clinical trial of 123 patients 18 years or older with advanced angiosarcoma that was conducted between February 16, 2017, and April 12, 2019, at 31 sites in the US and the European Union. Patients were randomized 1:1 to receive pazopanib alone or carotuximab plus pazopanib. The trial incorporated an adaptive enrichment design. Inclusion criteria were no more than 2 prior lines of systemic therapy and an Eastern Cooperative Oncology Group performance status of 0 or 1. The efficacy analysis used the intent-to-treat population; the safety analysis included all patients who received a dose of either study drug.. Oral pazopanib, 800 mg/d, or intravenous carotuximab, 10 mg/kg, administered weekly, plus oral pazopanib, 800 mg/d, with dose modification allowed per patient tolerance or until disease progression.. The primary end point was PFS, assessed by blinded independent radiographic and cutaneous photographic review per Response Evaluation Criteria in Solid Tumors (RECIST) guidelines, version 1.1. Secondary end points included the objective response rate and overall survival. An interim analysis to determine the final sample size was conducted after enrollment of 123 patients. PFS in the group receiving pazopanib alone was compared with PFS in the group receiving carotuximab plus pazopanib using the log rank test.. Of 114 patients with evaluable data (53 in the pazopanib arm and 61 in the carotuximab plus pazopanib arm), 69 (61%) were female and the median age was 68 years (range, 24-82 years); 57 (50%) had cutaneous disease and 32 (28%) had had no prior treatment. The primary end point (PFS) was not reached (hazard ratio [HR], 0.98; 95% CI, 0.52-1.84; P = .95), with a median of 4.3 months (95% CI, 2.9 months to not reached) for pazopanib and 4.2 months (95% CI, 2.8-8.3 months) for the combination arm. The most common all-grade adverse events in the single-agent pazopanib arm vs the combination arm were fatigue (29 patients [55%] vs 37 [61%]), headache (12 patients [23%] vs 39 [64%]), diarrhea (27 patients [51%] vs 35 [57%]), nausea (26 patients [49%] vs 29 [48%]), vomiting (12 patients [23%] vs 23 [38%]), anemia (5 patients [9%] vs 27 [44%]), epistaxis (2 patients [4%] vs 34 [56%]), and hypertension (29 patients [55%] vs 22 [36%]).. In this phase 3 randomized clinical trial, carotuximab plus pazopanib did not improve PFS compared with pazopanib alone in patients with advanced angiosarcoma.. ClinicalTrials.gov Identifier: NCT02979899.

Topics: Aged; Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Female; Hemangiosarcoma; Humans; Indazoles; Male; Pyrimidines; Sulfonamides

Angiosarcomas are rare mesenchymal sarcomas that can present as primary cutaneous or noncutaneous disease. They express a variety of vascular endothelial growth factor receptors. The authors hypothesized that the treatment of angiosarcoma with pazopanib, a multikinase inhibitor with activity against vascular endothelial growth factor receptors, would result in disease response and prolonged disease stabilization.. This was an open-label, phase 2 trial of pazopanib in patients who had incurable angiosarcoma. The co-primary end points were response according to the Response Evaluation Criteria in Solid Tumors and progression-free survival (PFS) at 3 months. The starting dose of pazopanib was 800 mg daily.. Twenty-nine patients were accrued between 2011 and 2018, and 22 patients were evaluable for response. Toxicities were similar to those identified in prior reports. There was one partial response (3%), and the clinical benefit rate (including complete responses, partial responses, and stable disease) was 48%, which was observed more frequently in patients who had cutaneous disease. The median PFS was 14.4 weeks, and the 3-month PFS rate determined by Kaplan-Meier estimate was 54.6% (95% CI, 36.0%-82.9%), meeting the primary study objective. The Kaplan-Meier overall survival estimate was 16.1 months.. Pazopanib therapy in patients who had incurable angiosarcoma was associated with meaningful disease control, especially in those who had cutaneous disease with limited objective responses.. Angiosarcoma is a rare cancer that can be found on the skin or in internal organs. This study tested pazopanib, an oral targeted medication, to determine its benefit in patients with angiosarcoma who could not undergo the removal of their tumors by surgery. Pazopanib treatment was safe, and no new side effects were reported. The study showed that pazopanib controlled tumor growth in one half of patients at 3 months and was more common in angiosarcomas of the skin; it led to tumor shrinkage in a minority of patients (1 of 29).

Topics: Hemangiosarcoma; Humans; Indazoles; Pyrimidines; Receptors, Vascular Endothelial Growth Factor; Sulfonamides; Treatment Outcome; Vascular Endothelial Growth Factor A

Major challenges in clinical trials of ultra-orphan oncology diseases include limited patient availability and paucity of reliable prior data for estimating the treatment effect and, therefore, determining optimal sample size. Angiosarcoma (AS), a particularly aggressive form of soft tissue sarcoma with an incidence of about 2000 cases per year in the United States and Europe is poorly addressed by current systemic therapies. Pazopanib, an inhibitor of vascular endothelial growth factor receptor (VEGFR) is approved for the treatment of AS, with modest benefit. TRC105 (carotuximab) is a monoclonal antibody to endoglin, an essential angiogenic target highly expressed on proliferating endothelium and both tumor vessels and tumor cells in AS, that has the potential to complement VEGFR tyrosine kinase inhibitors. In a phase I/II study of soft tissue sarcoma, TRC105 combined safely with pazopanib and the combination demonstrated durable complete responses and encouraging progression-free survival (PFS). In addition, there was a suggestion of superior benefit in patients with cutaneous lesions versus those with the non-cutaneous lesions.. This article describes the design of a recently initiated phase III trial of TRC105 And Pazopanib versus Pazopanib alone in patients with advanced AngioSarcoma (TAPPAS trial). Given the ultra-orphan status of the disease and the paucity of reliable prior data on PFS or overall survival (end points required for regulatory approval as a pivotal trial), an adaptive design incorporating population enrichment and sample size re-estimation was implemented. The design incorporated regulatory input from the Food and Drug Administration (FDA) and European Medicines Agency and proceeded following special protocol assessment designation by the FDA.. It is shown that the benefit of the adaptive design as compared with a conventional single-look design arises from the learning and subsequent improvements in power that occur after an unblinded analysis of interim data.. NCT02979899.

Topics: Antibodies, Monoclonal; Antineoplastic Combined Chemotherapy Protocols; Epidemiologic Research Design; Follow-Up Studies; Hemangiosarcoma; Humans; Indazoles; Patient Selection; Prognosis; Pyrimidines; Sulfonamides; Survival Rate

Pazopanib is a multitargeted tyrosine kinase inhibitor approved for the treatment of patients with selective subtypes of advanced soft tissue sarcoma (STS) who have previously received standard chemotherapy including anthracyclines. Data on the efficacy in vascular sarcomas are limited. The main objective of this study was to investigate the activity of pazopanib in vascular sarcomas.. A retrospective study of patients with advanced vascular sarcomas, including angiosarcoma (AS), epithelioid hemangioendothelioma (HE) and intimal sarcoma (IS) treated with pazopanib in real life practice at EORTC centers as well as patients treated within the EORTC phase II and III clinical trials (62043/62072) was performed. Patient and tumor characteristics were collected. Response was assessed according to RECIST 1.1. and survival analysis was performed.. Fifty-two patients were identified, 40 (76.9%), 10 (19.2%) and two (3.8%) with AS, HE and IS, respectively. The response rate was eight (20%), two (20%) and two (100%) in the AS, HE and IS subtypes, respectively. There was no significant difference in response rate between cutaneous and non-cutaneous AS and similarly between radiation-associated and non-radiation-associated AS. Median progression-free survival (PFS) and median overall survival (OS; from commencing pazopanib) were three months (95% CI 2.1-4.4) and 9.9 months (95% CI 6.5-11.3) in AS, respectively.. The activity of pazopanib in AS is comparable to its reported activity in other STS subtypes. In this study, the activity of pazopanib was similar in cutaneous/non-cutaneous and in radiation/non-radiation-associated AS. In addition, pazopanib showed promising activity in HE and IS, worthy of further evaluation.

Topics: Adult; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Female; Follow-Up Studies; Hemangioendothelioma, Epithelioid; Hemangiosarcoma; Humans; Indazoles; Lymphatic Metastasis; Male; Middle Aged; Neoplasm Staging; Neoplasms; Prognosis; Pyrimidines; Retrospective Studies; Sulfonamides; Survival Rate; Tunica Intima

Cutaneous angiosarcoma (CAS) is a rare and highly aggressive type of vascular tumor. Although chemoradiotherapy with taxanes is recognized as a first-line therapy for CAS, second-line therapy for CAS remains controversial. From the above findings, the efficacy and safety profiles of taxane-switch (change paclitaxel to docetaxel or vise), eribulin methylate, and pazopanib regimens in second-line chemotherapy were evaluated retrospectively in 50 Japanese taxane-resistant CAS patients. Although there was no significant difference in progression-free survival (P = 0.3528) among the regimens, the incidence of all adverse events (AEs) (P = 0.0386), as well as severe G3 or more AEs (P = 0.0477) was significantly higher in the eribulin methylate group and pazopanib group than in the taxane-switch group. The present data suggest that switching to another taxane should be considered for the treatment of taxane-resistant CAS in second-line therapy based on the safety profiles.

Topics: Antineoplastic Combined Chemotherapy Protocols; Drug Resistance, Neoplasm; East Asian People; Female; Hemangiosarcoma; Humans; Paclitaxel; Retrospective Studies; Skin Neoplasms; Taxoids

Angiosarcoma is a highly aggressive mesenchymal tumor. Although systemic chemotherapy is often considered for the inoperable or metastatic angiosarcoma, the outcome of such treatment is unsatisfactory and poorly delineated.. We reviewed electronic medical records of 75 patients with angiosarcoma who were treated with systemic chemotherapy for inoperable or metastatic disease. Patients were classified as having liver involvement if they had either primary or metastatic hepatic lesions.. Among the patients evaluated, 51 patients (68%) were male and 24 patients (32%) had primary cutaneous angiosarcoma. Liver involvement was present in 28 patients (37.3%). A total of 59 patients received first-line weekly paclitaxel (wPac) and showed an objective response rate (ORR) of 23.7% (n=14), a median progression-free survival (mPFS) of 4.0 months (95% confidence interval [CI], 3.0 to 6.1), and a median overall survival (mOS) of 10.2 months (95% CI, 7.0 to 14.6). Among patients without liver involvement, patients receiving wPac (n=35) had significantly prolonged mPFS (5.8 months vs. 3.2 months, respectively; p=0.014) with a tendency for prolonged mOS (13.8 months vs. 11.6 months, respectively; p=0.13) than those receiving other regimens (n=12). A total of 24 patients received second- or later-line pazopanib monotherapy and showed an ORR of 16.7% (n=4), a mPFS of 2.4 months (95% CI, 1.8 to 4.3) and a mOS of 5.4 months (95% CI, 3.5 to not available).. Treatment with first-line wPac and later-line pazopanib seems to provide survival benefit, especially for patients with advanced angiosarcoma without liver involvement.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Female; Follow-Up Studies; Hemangiosarcoma; Humans; Indazoles; Liver Neoplasms; Male; Middle Aged; Paclitaxel; Prognosis; Pyrimidines; Retrospective Studies; Skin Neoplasms; Sulfonamides; Survival Rate

Topics: Aged; Angiogenesis Inhibitors; Duodenal Ulcer; Fatal Outcome; Female; Gastrointestinal Hemorrhage; Hemangiosarcoma; Humans; Indazoles; Lung Neoplasms; Lymphangiosarcoma; Pyrimidines; Stomach Ulcer; Sulfonamides

Topics: Hemangiosarcoma; Humans; Indazoles; Pyrimidines; Skin Neoplasms; Sulfonamides

Topics: Hemangiosarcoma; Humans; Indazoles; Interleukin-2; Pyrimidines; Scalp; Skin Neoplasms; Sulfonamides

Paclitaxel is a standard of care for patients with primary cutaneous angiosarcoma of the scalp and face. However, no standard second-line treatment for paclitaxel-resistant patients has ever been established. Since primary cutaneous angiosarcoma expresses a high level of vascular endothelial growth factor receptor, the multitargeted tyrosine kinase inhibitor pazopanib seemed to be the most promising agent, and several retrospective studies have demonstrated its activity against this disease. However, the efficacy and safety of pazopanib in paclitaxel-resistant patients with primary cutaneous angiosarcoma have never been evaluated in a clinical trial.. In February 2018 the Dermatologic Oncology Group of Japan Clinical Oncology Group started a single-arm confirmatory trial to evaluate the efficacy and safety of pazopanib as a second-line treatment for patients with primary cutaneous angiosarcoma whose disease was resistant to paclitaxel or who were unable to tolerate paclitaxel (JCOG1605, JCOG-PCAS). Patients with primary cutaneous angiosarcoma not associated with lymphedema or radiation, progressing despite first-line paclitaxel monotherapy are included in the study. No prior systemic chemotherapy other than paclitaxel is permitted. Pazopanib is administered orally at an initial dosage of 800 mg once daily. Dose modifications for adverse events are made according to the dose reduction criteria described in the protocol. Treatment is continued until recurrence, disease progression, unacceptable toxic effects, patient refusal, or death. The primary endpoint is progression-free survival, secondary endpoints include overall survival, response rate, disease control rate, adverse events, and serious adverse events. We plan to recruit 30 participants in 5.5 years from 23 Japanese institutions. The follow-up period is set as 1 year after completion of accrual. The study protocol was approved by the Japan Clinical Oncology Group Protocol Review Committee in December 2017. Ethical approval for this study was granted by Ethics Committee of each institute.. If the primary endpoint is met, pazopanib will be regarded as a standard of care for paclitaxel-resistant patients for whom no standard second-line treatment is established.. Registry number: UMIN000031438 [ http://www.umin.ac.jp/ctr/index.htm ]. Date of Registration: 23/Feb/2018. Date of First Participant Enrollment: 8/Mar/2018.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents, Phytogenic; Drug Resistance, Neoplasm; Female; Follow-Up Studies; Hemangiosarcoma; Humans; Indazoles; Male; Middle Aged; Paclitaxel; Prognosis; Pyrimidines; Research Design; Salvage Therapy; Skin Neoplasms; Sulfonamides; Young Adult

The growing population of young cancer survivors and a trend toward postponing pregnancy until later years in life are leading to a deeper attention towards understanding treatment-induced sequelae, and, in particular, the effects of cancer and/or treatment on fertility. Nowadays, the infertility risks potentially associated with molecular targeted therapies are not established, and clinical reports are sparse. Moreover, the increasing use of molecular targeted drugs in the adjuvant setting and in diseases with better prognosis makes preservation of fertility a major topic in current research.. Here, we report the case of an 18-year-old woman, with a 3-cm superficial lump of the right breast, who had no remarkable family or medical history. Menarche had occurred at the age of 14 years, with normal regular periods.. High-grade angiosarcoma, with metastatic progression and multiple relapse, was diagnosed.. After diagnosis, right radical mastectomy was carried out with no evidence of residual disease. No adjuvant treatment was delivered. Lymph node metastasis were found later and chemotherapy with doxorubicin 25 mg/m/day and ifosfamide 1 g/m/day (both on days 1-3) every 21 days was administered. During treatment, the patient reported menstrual irregularities but no amenorrhea. Due to further local relapse a few years later, the patient was treated for progressive metastatic disease with gemcitabine 1000 mg/m on days 1 and 8 every 21 days for 6 cycles, and underwent surgery, followed by pegylated liposomal doxorubicin, 50 mg/m on day 1 every 28 days. After further disease progression 5 years after first diagnosis, pazopanib was administered at a dose of 800 mg daily for 10 months.. The patient experienced a transient ovarian insufficiency possibly due to pazopanib. Since amenorrhea developed within 2 months from the initiation of pazopanib treatment and menses returned regularly only after discontinuation of the treatment itself.. This is the first case report that strongly suggests a correlation between pazopanib exposure and development of ovarian insufficiency. Our case tantalizes to inspire additional preclinical and clinical research on the true incidence, possible dose dependence, and reversibility of pazopanib (and other TKIs) -induced ovarian failure.

Topics: Adolescent; Breast Neoplasms; Combined Modality Therapy; Endosonography; Female; Hemangiosarcoma; Humans; Indazoles; Mastectomy; Primary Ovarian Insufficiency; Pyrimidines; Receptors, Vascular Endothelial Growth Factor; Sulfonamides; Vagina

Topics: Aged; Amputation Stumps; Amputation, Surgical; Biopsy; Chemoradiotherapy; Disease Progression; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Hemangiosarcoma; Humans; Indazoles; Leg; Lymphangiosarcoma; Neoplasm Recurrence, Local; Progression-Free Survival; Protein Kinase Inhibitors; Pyrimidines; Skin; Skin Neoplasms; Sulfonamides

Topics: Angiogenesis Inhibitors; Apoptosis; Cell Line, Tumor; Cell Survival; Dermis; Endothelium, Vascular; Fibroblasts; Hemangiosarcoma; Human Umbilical Vein Endothelial Cells; Humans; Indazoles; Pyrimidines; Skin Neoplasms; Sulfonamides; Toxicity Tests

Primary hepatic angiosarcoma (PHA) is a rare and aggressive solid tumor, with high rates of local recurrence and distant metastasis, and poor prognosis. There are no established treatment guidelines for PHA.. A 78-year-old asymptomatic man with PHA that was successfully treated with pazopanib plus PD-1 inhibitor and RetroNectin-activated killer cells (RAK cells). After one month of treatment, there was a clear reduction in the size and number of the liver metastases; and after nearly 15 months, most of the lesions were stable, no new lesions had developed, and the side effect of treatment was minor.. Pazopanib, PD-1 inhibitor and RAK cells could serve as a potential option for the treatment of advanced PHA.

Topics: Aged; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Biopsy; Cell Line, Tumor; Combined Modality Therapy; Hemangiosarcoma; Humans; Immunohistochemistry; Immunotherapy, Adoptive; Indazoles; Liver Neoplasms; Magnetic Resonance Imaging; Male; Neoplasm Metastasis; Neoplasm Staging; Programmed Cell Death 1 Receptor; Pyrimidines; Sulfonamides; Treatment Outcome

Peritoneal angiosarcoma is an extremely rare sarcoma (0.01287% incidence per 100,000) with an aggressive course and a poor prognosis. In this case, the manifestation of peritoneal angiosarcoma was ascites, which caused difficulty in early diagnosis and the diagnosis of peritoneal angiosarcoma, was made only after the surgery.. A 61-year-old man working in Mainland China presented with a 1-month history of abdominal distension. A contrast-enhanced abdominal computed tomography (CT) scan revealed peritoneal carcinomatosis with massive ascites. However, his tuberculosis (TB) polymerase chain reaction was negative. The ascites cell block and cytology also revealed negative for malignant cells. The patient underwent intra-abdominal tumor excision. After the operation, the patient's blood pressure (BP) dropped. Due to the state of shock, he was transferred to an intensive care unit (ICU).. According to the pathology report, the neoplastic cells were positive for cytokeratin, cluster of differentiation 31 (CD31), cluster of differentiation 34 (CD34), and negative for cytokeratin 7 (CK7), cytokeratin 7 (CK20). Therefore, the diagnosis of epithelioid angiosarcoma was made.. The patient took 400 mg of Pazopanib once a day.. Even though vasopresser was used, the patient's BP was still low. Finally, he expired.. Initialy, the patient presented with abdominal distension and large amount of ascites in the beginning. TB peritonitis was highly suspected after the abdominal CT scan. Therefore, surgical procedures would be essential in the identification of proper diagnosis. In the future, the diagnosis of peritoneal epithelioid angiosarcoma should also be taken into consideration for patients with abnormal ascites besides the common diagnoses of TB, liver cirrhosis, and infection.

Topics: Ascites; Hemangiosarcoma; Humans; Hypotension; Indazoles; Male; Middle Aged; Peritoneal Neoplasms; Postoperative Complications; Pyrimidines; Receptors, Vascular Endothelial Growth Factor; Sulfonamides; Tomography, X-Ray Computed

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

Pazopanib is a potent and selective multi-targeted tyrosine kinase inhibitor that has been reported to extend progression-free survival in cases of metastatic soft-tissue sarcoma. However, the efficacy of pazopanib for cutaneous angiosarcoma has not been confirmed. We report eight cases of angiosarcoma treated with pazopanib, and review the efficacy and safety of pazopanib therapy. We retrospectively investigated the clinical information, including age, sex, body surface area, location, performance status, lung or pleural metastasis, preceding treatment, oral dose of pazopanib, response rate, progression-free survival and adverse effects. Five of the eight patients needed to stop the pazopanib treatment due to severe adverse effects, including thrombocytopenia, anemia, drug-associated pancreatitis, acute fulminant hepatitis and general fatigue. Progression-free survival ranged 0.5-3.5 months (mean ± standard deviation, 1.81 ± 1.03). Overall survival ranged 3-26 months (14.13 ± 9.47). Six of the eight cases showed progressive disease, and two of the eight cases showed stable disease. To assess overall survival in angiosarcoma treated with pazopanib, we compared the pazopanib-treated group (n = 8) with the non-pazopanib-treated control group (n = 10). There was no significant difference between two groups (P = 0.19, log-rank test). In conclusion, our case series suggests that pazopanib does not bring remarkable improvement in patients with angiosarcoma.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anemia; Chemical and Drug Induced Liver Injury; Disease-Free Survival; Fatigue; Female; Hemangiosarcoma; Humans; Indazoles; Male; Protein Kinase Inhibitors; Protein-Tyrosine Kinases; Pyrimidines; Retrospective Studies; Sulfonamides; Thrombocytopenia; Treatment Outcome

Topics: Aged; Angiogenesis Inhibitors; Disease Progression; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Indazoles; Male; Pyrimidines; Skin Neoplasms; Sulfonamides

Angiosarcoma is a malignant neoplastic disease originating from or differentiating toward vascular endothelium, for which systemic pharmacologic treatment has limited durability. The molecular oncogenesis of angiosarcoma is often linked to inappropriate activations of vascular endothelial growth factor receptor (VEGFR) family members, which presents an opportunity for the use of therapy that selectively targets the machinery of vascular signaling.. Hybridization capture of 3,320 exons of 182 cancer-related genes and the introns of 14 genes frequently rearranged in cancer was applied to more than 50 ng of DNA extracted from a formalin-fixed, paraffin-embedded biopsy of recurrent angiosarcoma and was sequenced to high, uniform coverage of 939x.. The angiosarcoma harbored amplifications of VEGFR2 (KDR) of 8 copies and VEGFR3 (FLT4) of 16 copies. The patient was initially treated with sorafenib, an inhibitor of VEGFR2, and developed progressive disease. The patient then received pazopanib, an inhibitor of VEGFR2 and VEGFR3 and experienced a potent antitumor response resulting in clinically stable disease for 6 months.. This exceptional response to pazopanib treatment suggests that a subset of patients with angiosarcoma with genomic alterations in vascular signaling genes may respond well to pazopanib.

Topics: Aged, 80 and over; Angiogenesis Inhibitors; Hemangiosarcoma; Humans; Indazoles; Male; Pyrimidines; Signal Transduction; Sulfonamides; Vascular Endothelial Growth Factor Receptor-2

Although cutaneous angiosarcoma (cAS) has one of the worst prognoses among malignant skin tumors, few effective drug options for secondary treatment have been discovered to date because of the limited number of cases. Therefore, this study was aimed at determining pazopanib's potential as a new cAS treatment option. We retrospectively evaluated five patients with taxane-resistant unresectable cAS treated with pazopanib at a university hospital. Their characteristics and treatment outcomes were retrieved from their records. Progression-free survival (PFS), overall survival (OS), disease progression, and toxicity were evaluated; furthermore, the response to pazopanib was assessed in relation to the expression of vascular endothelial growth factor receptor 2 (VEGFR-2). The median PFS from the time of pazopanib initiation was 94 days. Two patients showed partial response, two showed stable disease, and one had progressive disease in the case of the best overall response. VEGFR-2 expression was positive in all cases, and patients with high expression had improved median OS compared to that in those with low expression. VEGFR-2 expression was correlated with a longer OS. The most common toxicities were hypertension and anorexia followed by myelosuppression. This is the largest case series reported wherein pazopanib was used for taxane-resistant cAS. Although the cytoreductive effect and survival benefits were not significant in this small sample, we consider pazopanib a valid treatment option for preserving patients' quality of life. Our results suggest pazopanib treatment slows the progression of disease and stabilizes it in patients with taxane-resistant cAS.

Topics: Aged; Aged, 80 and over; Angiogenesis Inhibitors; Bridged-Ring Compounds; Disease-Free Survival; Drug Resistance, Neoplasm; Female; Hemangiosarcoma; Humans; Indazoles; Male; Middle Aged; Pyrimidines; Retrospective Studies; Skin Neoplasms; Sulfonamides; Taxoids

Topics: Administration, Oral; Aged; Aged, 80 and over; Angiogenesis Inhibitors; Female; Hemangiosarcoma; Humans; Indazoles; Male; Neoplasm Recurrence, Local; Protein Kinase Inhibitors; Pyrimidines; Skin Neoplasms; Sulfonamides; Treatment Outcome

Topics: Aged, 80 and over; Angiogenesis Inhibitors; Antineoplastic Agents; Female; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Indazoles; Protein Kinase Inhibitors; Pyrimidines; Quality of Life; Scalp; Skin Neoplasms; Sulfonamides

Topics: Angiogenesis Inhibitors; Head and Neck Neoplasms; Hemangiosarcoma; Humans; Indazoles; Male; Middle Aged; Pyrimidines; Scalp; Skin Neoplasms; Sulfonamides

Topics: Adrenal Cortex Hormones; Adult; Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Delayed Diagnosis; Diagnostic Errors; Doxorubicin; Drug Resistance, Neoplasm; Etoposide; Heart Neoplasms; Hemangiosarcoma; Humans; Ifosfamide; Indazoles; Lymphoma, Non-Hodgkin; Magnetic Resonance Imaging; Male; Myocardium; Paclitaxel; Pericardial Effusion; Pericardiocentesis; Pericarditis; Pericardium; Protein Kinase Inhibitors; Pulmonary Embolism; Pyrimidines; Remission Induction; Sulfonamides; Vincristine