Phase I Trial of Neoadjuvant Conformal Radiotherapy Plus Sorafenib for Patients with Locally Advanced Soft Tissue Sarcoma of the Extremity

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• 作者：Robert J. Canter MD (1)
  Dariusz Borys MD (2)
  Abimbola Olusanya PhD (1)
  Chin-Shang Li PhD (3)
  Li-Yuan Lee BA (4)
  Robert D. Boutin MD (5)
  Scott D. Christensen MD (6)
  Robert M. Tamurian MD (7)
  Arta M. Monjazeb MD ; PhD (8)
  
• 刊名：Annals of Surgical Oncology
• 出版年：2014
• 出版时间：May 2014
• 年：2014
• 卷：21
• 期：5
• 页码：1616-1623
• 全文大小：294 KB
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• 作者单位：Robert J. Canter MD (1)
  Dariusz Borys MD (2)
  Abimbola Olusanya PhD (1)
  Chin-Shang Li PhD (3)
  Li-Yuan Lee BA (4)
  Robert D. Boutin MD (5)
  Scott D. Christensen MD (6)
  Robert M. Tamurian MD (7)
  Arta M. Monjazeb MD, PhD (8)
  
  1. Division of Surgical Oncology, UC Davis Comprehensive Cancer Center, University of California Davis Medical Center, Sacramento, CA, USA
  2. Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, Sacramento, CA, USA
  3. Division of Biostatistics, Department of Public Health Sciences, University of California Davis, Sacramento, CA, USA
  4. Department of Psychology, University of Michigan, Ann Arbor, MI, USA
  5. Department of Radiology, University of California Davis Medical Center, Sacramento, CA, USA
  6. Division of Hematology/Oncology, Department of Internal Medicine, University of California Davis Medical Center, Sacramento, CA, USA
  7. Division of Orthopedic Oncology, Department of Orthopedic Surgery, University of California Davis Medical Center, Sacramento, CA, USA
  8. Department of Radiation Oncology, University of California Davis Medical Center, Sacramento, CA, USA
  
• ISSN：1534-4681

文摘

Background Despite effective local therapy with surgery and radiotherapy (RT), ~50?% of patients with high-grade soft tissue sarcoma (STS) will relapse and die of disease. Since experimental data suggest a significant synergistic effect when antiangiogenic targeted therapies such as sorafenib are combined with RT, we chose to evaluate preoperative combined modality sorafenib and conformal RT in a phase I/II trial among patients with extremity STS amenable to treatment with curative intent. Methods For the phase I trial, eight patients with intermediate- or high-grade STS?>5?cm in maximal dimension or low-grade STS?>8?cm in maximal dimension received concomitant sorafenib (dose escalation cohort 1:200 twice daily, cohort 2:200/400 daily) and preoperative RT (50?Gy in 25 fractions). Sorafenib was continued during the entire period of RT as tolerated. Surgical resection was completed 4-?weeks following completion of neoadjuvant sorafenib/RT. Three sorafenib dose levels were planned. Primary endpoints of the phase I trial were maximal tolerated dose and dose-limiting toxicity (DLT). Results Eight patients were enrolled in the phase I (five females, median age 44?years, two high-grade pleomorphic, two myxoid/round cell liposarcoma, four other). Median tumor size was 16?cm (range 8-9), and all tumors were located in the lower extremity. Two of five patients treated at dose level 2 developed DLT consisting of grade 3 rash not tolerating drug reintroduction. Other grade 3 side effects included anemia, perirectal abscess, and supraventricular tachycardia. Radiation toxicity (grade 1 or 2 dermatitis; N?=?8) and post-surgical complications (three grade 3 wound complications) were comparable to historical controls and other series of preoperative RT monotherapy. Complete pathologic reponse (?5?% tumor necrosis) was observed in three patients (38?%). Conclusion Neoadjuvant sorafenib in combination with RT is tolerable and appears to demonstrate activity in locally advanced extremity STS. Further study to determine efficacy at dose level 1 is warranted. (ClinicalTrials.gov identifier NCT00805727).