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Pazopanib and rhabdomyosarcoma

Vivek Subbiah, Christian Meyer, Ralph Zinner, Funda Meric-Bernstam, Marianna L Zahurak, Ashley O'Connor, Jason Roszik, Kenna Shaw, Joseph A Ludwig, Razelle Kurzrock, Nilofer A Azad
Purpose: Pazopanib, a multireceptor tyrosine kinase inhibitor targeting primarily VEGFRs1-3, is approved for advanced soft tissue sarcoma (STS) and renal cell cancer. Downstream of VEGFR, trametinib is an FDA-approved MEK inhibitor used for melanoma. We hypothesized that vertical pathway inhibition using trametinib would synergize with pazopanib in advanced STS. Experimental Design: In an open-label, multicenter, investigator-initiated National Comprehensive Cancer Network (NCCN)-sponsored trial, patients with metastatic or advanced STS received pazopanib 800 mg and 2 mg of trametinib continuously for 28-day cycles...
August 1, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Kwai Han Yoo, Hyo Song Kim, Su Jin Lee, Se Hoon Park, Sung Joo Kim, Soo Hee Kim, Yoon La Choi, Kyoo-Ho Shin, Yong Jin Cho, Jeeyun Lee, Sun Young Rha
BACKGROUND: We retrospectively reviewed outcomes of treatment with pazopanib, an oral multi-tyrosine kinase angiogenesis inhibitor, in patients with advanced soft tissue sarcoma, a rare and heterogeneous tumor group with limited treatment options. METHODS: Between 2009 and 2013, 43 patients with metastatic soft tissue sarcoma received pazopanib as salvage chemotherapy after one or more cytotoxic regimens. Response rate, progression-free survival, and overall survival were analyzed according to histological subtype, Eastern Cooperative Oncology Group performance status, and metastatic site...
2015: BMC Cancer
Nancy El-Bared, Philip Wong, Dian Wang
Since adjuvant radiotherapy was introduced in the 1970s for soft tissue sarcoma (STS), sequential clinical trials characterized the toxicities induced by radiotherapy when given post-operatively and pre-operatively. Gradual technological advancements led to more precise radiotherapy delivery through intensity-modulated radiation therapy (IMRT) and more accurate targeting through image-guided radiotherapy (IGRT) to minimize normal tissues from high-dose irradiation. These improvements ultimately reduced the long-term toxicities from radiotherapy...
May 2015: Current Treatment Options in Oncology
Akari Hashimoto, Kohichi Takada, Rishu Takimoto, Hiroto Horiguchi, Tsutomu Sato, Satoshi Iyama, Kazuyuki Murase, Kaoru Ono, Ayumi Tatekoshi, Tsuyoshi Hayashi, Koji Miyanishi, Yasushi Sato, Masayoshi Kobune, Yasuo Hirayama, Hiroshi Kitamura, Katsuya Nakanishi, Naoya Masumori, Tadashi Hasegawa, Junji Kato
Pazopanib, an oral tyrosine kinase inhibitor, is the first molecular-targeted agent approved for the treatment of advanced soft tissue sarcoma(STS). Rhabdomyosarcoma in adults is rare, accounting for less than 3%of all adult STS cases. A 57-year old woman presented with cervical lymphadenopathy. Computed tomography revealed a heterogeneous mass in the retroperitoneum, replacing the entire right kidney. On the basis of the above findings, the patient was diagnosed with alveolar rhabdomyosarcoma. She was first treated with 4 courses of vincristine, actinomycin D, and cyclophosphamide(VAC), which resulted in a partial response...
August 2014: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Michael Ferguson, Pooja Hingorani, Abha A Gupta
Within the context of modern cooperative group trials, modification of standard cytotoxic chemotherapy has not improved survival in patients with rhabdomyosarcoma (RMS) over the last 30 years. There is need and interest to incorporate novel targeted anticancer agents into the treatment plans for children and adolescents with newly diagnosed RMS; however, targets directly driven by FOXO1 translocation remain elusive, and molecular events driving translocation negative tumors similarly remain ill-defined. Thus, alternate pathways driving the tumors require identification and targeting...
2013: American Society of Clinical Oncology Educational Book
Stephen T Keir, Christopher L Morton, Jianrong Wu, Raushan T Kurmasheva, Peter J Houghton, Malcolm A Smith
Pazopanib is an oral angiogenesis inhibitor targeting vascular growth factor receptor-1, -2, and -3, platelet derived growth factor receptor-α, platelet derived growth factor receptor-β, and KIT that has demonstrated activity against a variety of adult cancer xenografts. Pazopanib was tested against a panel of pediatric rhabdomyosarcoma and Ewing sarcoma xenografts at a dose of 108 mg/kg/day or 100 mg/kg twice daily, administered orally for 28 days. While no objective responses were observed, pazopanib induced statistically significant differences in event-free survival compared to controls in approximately one-half of the sarcoma xenograft models tested...
September 2012: Pediatric Blood & Cancer
Sushil Kumar, Reza Bayat Mokhtari, Reihaneh Sheikh, Bing Wu, Libo Zhang, Ping Xu, Shan Man, Indhira Dias Oliveira, Herman Yeger, Robert S Kerbel, Sylvain Baruchel
PURPOSE: Low dose metronomic (LDM) chemotherapy, combined with VEGF signaling pathway inhibitors, is a highly effective strategy to coordinately inhibit angiogenesis and tumor growth in many adult preclinical cancer models. We have tested the efficacies of daily oral LDM topotecan alone and in combination with pazopanib, a VEGF receptor inhibitor, in three pediatric extracranial solid tumor mouse models. EXPERIMENTAL DESIGN: In vitro dose-response study of topotecan and pazopanib was conducted on several neuroblastoma, osteosarcoma, and rhabdomyosarcoma cell lines...
September 1, 2011: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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