title: Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial: A TITE-CRM Phase I/II Clinical Trial.
abstract: BACKGROUND
  Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with RRx-001 and whole brain radiotherapy (WBRT) without neurologic or systemic toxicity in the context of a phase I/II clinical trial. RRx-001 is an reactive oxygen and reactive nitrogen species (ROS/RNS)-dependent systemically nontoxic hypoxic cell radiosensitizer with vascular normalizing properties under investigation in patients with various solid tumors including those with brain metastases.
  
  
  CONCLUSIONS
  Metastatic melanoma to the brain is historically associated with poor outcomes and a median survival of 4 to 5 months. WBRT is a mainstay of treatment for patients with multiple brain metastases, but no significant therapeutic advances for these patients have been described in the literature. To date, candidate radiosensitizing agents have failed to demonstrate a survival benefit in patients with brain metastases, and in particular, no agent has demonstrated improved outcome in patients with metastatic melanoma. Kim et al. report two patients with melanoma metastases to the brain that responded to treatment with novel radiosensitizing agent RRx-001 and WBRT without neurologic or systemic toxicity in the context of a phase I/II clinical trial.
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA. Electronic address: michekim@med.umich.edu.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Kim
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Hemant
authors.initials: H
authors.lastname: Parmar
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Yue
authors.initials: Y
authors.lastname: Cao
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Pramanik
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Schipper
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: James
authors.initials: J
authors.lastname: Hayman
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Larry
authors.initials: L
authors.lastname: Junck
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Aaron
authors.initials: A
authors.lastname: Mammoser
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Heth
authors.affiliation: Walter Reed National Military Medical Center, 8901 Wisconsin Ave, Bethesda, MD, 20889, USA.
authors.forename: Corey A
authors.initials: CA
authors.lastname: Carter
authors.affiliation: InterWest Partners, 2710 Sand Hill Rd #200, Menlo Park, CA, 94025, USA.
authors.forename: Arnold
authors.initials: A
authors.lastname: Oronsky
authors.affiliation: Stanford University School of Medicine, Radiation Oncology, 875 Blake Wilbur Dr Clinic D, Stanford, CA, 94305, USA.
authors.forename: Susan J
authors.initials: SJ
authors.lastname: Knox
authors.affiliation: EpicentRx Inc., 800W El Camino Real, Suite 180, Mountain View, CA, 94040, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Caroen
authors.affiliation: EpicentRx Inc., 800W El Camino Real, Suite 180, Mountain View, CA, 94040, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Oronsky
authors.affiliation: EpicentRx Inc., 800W El Camino Real, Suite 180, Mountain View, CA, 94040, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Scicinski
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Theodore S
authors.initials: TS
authors.lastname: Lawrence
authors.affiliation: University of Michigan, 1500 E Medical Center Drive, Ann Arbor, MI, 48109, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Lao