Phase I Trial of Bortezomib and Concurrent External Beam Radiation in Patients With Advanced Solid Malignancies

Journal Article · Fri Oct 01 00:00:00 EDT 2010 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2009.07.1715· OSTI ID:21436196

Pugh, Thomas J; Changhu, Chen; Rabinovitch, Rachel ^[1]; Eckhardt, S Gail ^[2]; Rusthoven, Kyle E ^[1]; Swing, Robyn ^[3]; Raben, David ^[1]

---

1. Department of Radiation Oncology, University of Colorado Denver and Health Science Center, Aurora, Colorado (United States)
2. Department of Medicine, University of Colorado Denver and Health Science Center, Aurora, Colorado (United States)
3. Clinical Investigations Core, University of Colorado Denver and Health Science Center, Aurora, Colorado (United States)

Purpose: To determine the maximal tolerated dose of bortezomib with concurrent external beam radiation therapy in patients with incurable solid malignant tumors requiring palliative therapy. Methods and Materials: An open label, dose escalation, phase I clinical trial evaluated the safety of three dose levels of bortezomib administered intravenously (1.0 mg/m{sup 2}, 1.3 mg/m{sup 2}, and 1.6 mg/m{sup 2}/ dose) once weekly with concurrent radiation in patients with histologically confirmed solid tumors and a radiographically appreciable lesion suitable for palliative radiation therapy. All patients received 40 Gy in 16 fractions to the target lesion. Dose-limiting toxicity was the primary endpoint, defined as any grade 4 hematologic toxicity, any grade {>=}3 nonhematologic toxicity, or any toxicity requiring treatment to be delayed for {>=}2 weeks. Results: A total of 12 patients were enrolled. Primary sites included prostate (3 patients), head and neck (3 patients), uterus (1 patient), abdomen (1 patient), breast (1 patient), kidney (1 patient), lung (1 patient), and colon (1 patient). The maximum tolerated dose was not realized with a maximum dose of 1.6 mg/m{sup 2}. One case of dose-limiting toxicity was appreciated (grade 3 urosepsis) and felt to be unrelated to bortezomib. The most common grade 3 toxicity was lymphopenia (10 patients). Common grade 1 to 2 events included nausea (7 patients), infection without neutropenia (6 patients), diarrhea (5 patients), and fatigue (5 patients). Conclusions: The combination of palliative external beam radiation with concurrent weekly bortezomib therapy at a dose of 1.6 mg/m{sup 2} is well tolerated in patients with metastatic solid tumors. The maximum tolerated dose of once weekly bortezomib delivered concurrently with radiation therapy is greater than 1.6 mg/m{sup 2}.

• OSTI ID: 21436196
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Vol. 78, Issue 2; Other Information: DOI: 10.1016/j.ijrobp.2009.07.1715; PII: S0360-3016(09)02823-5; Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
ABDOMEN
ANTINEOPLASTIC DRUGS
CLINICAL TRIALS
DIARRHEA
FATIGUE
HEAD
KIDNEYS
LYMPHOPENIA
METASTASES
NECK
NEOPLASMS
PROSTATE
RADIATION DOSES
RADIOTHERAPY
TOXICITY
UTERUS
BODY
DISEASES
DOSES
DRUGS
FEMALE GENITALS
GLANDS
HEMIC DISEASES
IMMUNE SYSTEM DISEASES
LEUKOPENIA
MALE GENITALS
MECHANICAL PROPERTIES
MEDICINE
NUCLEAR MEDICINE
ORGANS
RADIOLOGY
SYMPTOMS
TESTING
THERAPY