pazopanib and Fibrosarcoma

Pazopanib, a tyrosine kinase inhibitor (TKI), is a standard treatment for various tumours, including metastatic non-adipocytic soft-tissue sarcomas. In literature, erythrocytosis has been described as a TKI-related condition.. A 59-year-old man underwent surgical removal of a sub-scapular mass consistent with myxofibrosarcoma. After distant relapse, he first started chemotherapy, and then Pazopanib. He was found to have increased levels of hemoglobin (Hb) and hematocrit (Hct). He was asymphtomatic, with no history of pulmonary disease nor smoking habit. Erythropoietin (EPO) level was higher than normal. A polycythemia vera was ruled out.. We postulated a Pazopanib-related secondary erythrocytosis, since Hb and Hct levels increased from baseline during treatment, then normalized when Pazopanib was discontinued. We used the Naranjo Nomogram to assess the correlation between the adverse effect and Pazopanib, the correlation was "Probable", a score of 5. To the best of our knowledge, this is the first case report of Pazopanib-related secondary polycythemia in a patient with sarcoma. It is important to pay attention to blood count and to any symptoms potentially related to erythrocytosis in patients treated with TKIs.

Topics: Angiogenesis Inhibitors; Fibroma; Fibrosarcoma; Humans; Indazoles; Male; Middle Aged; Polycythemia; Protein Kinase Inhibitors; Pyrimidines; Soft Tissue Neoplasms; Sulfonamides

Myxofibrosarcoma (MFS) is the most common sarcomas in elderly patients and is either chemo-resistant or recurs with metastasis after chemotherapy. This recalcitrant cancer in need of improved treatment. We have established a patient-derived orthotopic xenograft (PDOX) of MFS. The MFS PDOX model was established in the biceps femoris of nude mice and randomized into 7 groups of 7 mice each: control; doxorubicin (DOX); pazopanib (PAZ); temozolomide (TEM); Irinotecan (IRN); IRN combined with TEM; IRN combined with cisplatinum (CDDP) and Salmonella typhimurium A1-R (S. typhimurium A1-R). Treatment was evaluated by relative tumor volume and relative body weight. The MFS PDOX models were DOX, PAZ, and TEM resistant. IRN combined with TEM and IRN combined with CDDP were most effective on the MFS PDOX. S. typhimurium A1-R arrested the MFS PDOX tumor. There was no significant body weight loss in any group. The present study suggests that the combination of IRN with either TEM or CDDP, and S. typhimurium have clinical potential for MFS.

Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Fibrosarcoma; Humans; Indazoles; Irinotecan; Male; Mice, Nude; Pyrimidines; Random Allocation; Salmonella Infections; Salmonella typhimurium; Sulfonamides; Temozolomide; Tumor Burden; Xenograft Model Antitumor Assays

We herein report the case of a patient presenting with myxofibrosarcoma (MFS) who underwent treatment with surgery, proton beam therapy (PBT), and pazopanib. A 64-year-old male was diagnosed with MFS, which ranged from the posterior neck to the shoulder. Surgery was performed as an initial treatment; however, the primary tumor recurred 83 months after the initial treatment. We, therefore, administered PBT. Although most of the recurrent tumor disappeared after PBT, multiple lung metastases were identified 3 months after the completion of PBT. We initiated antiangiogenic treatment with pazopanib. Although long-term survival was achieved with the treatments, the patient suffered from a skin ulcer and soft tissue necrosis and eventually died of general prostration caused by infection, and complicated by pneumonia. Although PBT and pazopanib were effective for treating the local recurrence and lung metastases of MFS, respectively, clinicians must be cognizant of the fact that the combination of high-dose irradiation and angiogenesis inhibitors, even in nonconcurrent cases, can result in a severe skin ulcer and soft tissue necrosis.

Topics: Angiogenesis Inhibitors; Debridement; Fatal Outcome; Fibrosarcoma; Head and Neck Neoplasms; Humans; Indazoles; Lung Neoplasms; Male; Middle Aged; Myxoma; Necrosis; Proton Therapy; Pyrimidines; Skin Ulcer; Soft Tissue Infections; Sulfonamides; Tomography, X-Ray Computed

Clinical and radiological diagnosis of infantile fibrosarcoma (IFS) is challenging because of its similarity to vascular origin tumors. Treatment involves complete resection. Although chemotherapy may allow more conservative resection, treatment guidelines are not strictly defined. One IFS patient with an unresectable tumor had disease progression during chemotherapy. A primary tumor sample showed high VEGFR-1/2/3 and PDGFR-α/β expression. After pazopanib therapy, most tumor showed necrosis within 29 days and could be removed completely, with no relapse in 8 months post-resection. When IFS features hypervascularity, VEGFR and PDGFR expression may be high, thus allowing consideration of VEGFR inhibitors such as pazopanib.

Topics: Angiogenesis Inhibitors; Axilla; Drug Resistance, Neoplasm; Fibrosarcoma; Humans; Indazoles; Infant; Male; Neoadjuvant Therapy; Pyrimidines; Receptors, Platelet-Derived Growth Factor; Receptors, Vascular Endothelial Growth Factor; Reverse Transcriptase Polymerase Chain Reaction; Sulfonamides

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