Neoadjuvant pazopanib in nonrhabdomyosarcoma soft tissue sarcomas (ARST1321): A report of major wound complications from the Children's Oncology Group and NRG Oncology
Mark L. Kayton, Department of Surgery, K. Hovnanian Children's Hospital at Jersey Shore University Medical Center, Hackensack-Meridian Health Network, Neptune, New Jersey, USA.
Aaron R. Weiss, Department of Pediatrics, Maine Medical Center, Portland, Maine, USA.
Wei Xue, Department of Biostatistics, University of Florida, Gainesville, Florida, USA.
Odion Binitie, Department of Sarcoma, Moffitt Cancer Center, Tampa, Florida, USA.
Andrea Hayes Dixon, Department of Surgery, Howard University, Washington, District of Columbia, USA.
R Lor Randall, Department of Orthopaedic Surgery, University of California Davis, Sacramento, California, USA.
Joel I. Sorger, Department of Orthopedic Surgery, Cincinnati Children's Hospital, Cincinnati, Ohio, USA.
Douglas S. Hawkins, Department of Pediatrics, University of Washington School of Medicine and Seattle Children's Hospital, Seattle, Washington, USA.
Sheri L. Spunt, Department of Pediatrics, Stanford University School of Medicine, Palo Alto, California, USA.
Dian Wang, Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois, USA.
Lynn Million, Department of Radiation Oncology, Stanford University School of Medicine, Palo Alto, California, USA.
Stephanie Terezakis, Department of Radiation Oncology, Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, USA.
Edwin Choy, Department of Medical Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Scott H. Okuno, Department of Oncology, Mayo Clinic, Rochester, Minnesota, USA.
Rajkumar Venkatramani, Department of Pediatrics, Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
Yen-Lin Chen, Department of Radiation Oncology, Massachusetts General Hospital, Boston, Massachusetts, USA.
Thomas J. Scharschmidt, Department of Orthopaedics, James Cancer Hospital and Nationwide Children's Hospital, Columbus, Ohio, USA.
BACKGROUND AND OBJECTIVES: The impact upon wound healing of targeted molecular therapies, when incorporated into neoadjuvant therapy of soft tissue sarcoma, is largely unknown. Here, we describe wound complications following addition of pazopanib, a tyrosine kinase inhibitor (TKI), to neoadjuvant radiotherapy (RT) +/- chemotherapy for soft tissue sarcoma. METHODS: Wound complications were evaluated on dose-finding and randomized arms of ARST1321, a phase II/III study incorporating neoadjuvant RT, +/- pazopanib, +/- ifosfamide/doxorubicin (ID) for sarcoma therapy. RESULTS: Of 85 evaluable patients, 35 (41%) experienced postoperative wound complications. Most (57%) were grade III. Randomization to pazopanib + RT + ID carried a 50% wound complication rate (17/34, with 47% grade III), compared to 22% (5/23) with ID + RT alone. In nonchemotherapy study arms, pazopanib + RT resulted in a 59% wound complication rate versus 25% for those receiving RT alone. Grade III wound complications occurred among 26% (15/58) of all patients receiving pazopanib. Wound complications occurred a median of 35 days postoperatively. Some occurred following diagnostic biopsies and at remote surgical sites. CONCLUSION: The addition of pazopanib to neoadjuvant chemotherapy and RT resulted in a higher wound complication rate following therapy of soft tissue sarcoma. The rate of grade III complications remained comparable to that reported in contemporary literature.