A phase I study of WR-2721 in combination with total body irradiation (TBI) in patients with refractory lymphoid malignancies

Journal Article · Wed Jan 01 04:00:00 EST 1992 · International Journal of Radiation Oncology, Biology and Physics; (United States)

OSTI ID:5514479

Coia, L; Krigel, R; Hanks, G; Comis, R; Algazy, K; Peters, R; McCulloch, W; Schien, P ^[1]

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1. Department of Radiation Oncology, Fox Chase Cancer Center/University of Pennsylvania, PA (United States)

This Phase I study was designed to establish the maximum tolerated dose (MTD) of WR-2721 when given twice weekly with total body irradiation (TBI) in the treatment of patients with advanced refractory lymphoid malignancies and to define the toxicities of this combination and schedule. Patients eligible for this study had advanced recurrent indolent non-Hodgkin's lymphoma (NHL) or chronic lymphocytic leukemia (CLL). Patients had symptomatic or progressive disease, a performance status of 0, 1, or 2, and adequate bone marrow, hepatic, and renal function. Only patients failing one or two regimens of prior chemotherapy were eligible. Patients who had received prior extended field irradiation were ineligible. Patients received TBI twice weekly (Tuesday and Friday) to a total of 10 doses at 15 cGy/fx. WR-2721 was given intravenously over 15 min beginning 30 min before irradiation. The escalation of WR-2721 was Level 1: 740 mg/m2 and Level 2: 910 mg/m2. The MTD of WR-2721 was that dose which produced predictable and reversible toxicity and would not interfere with patient well-being. Seven patients were entered onto the study, three at 740 mg/m2 and four at 910 mg/m2. Five patients had CLL and two patients small lymphocytic NHL. No patient had hypotension or nausea requiring reduction in dose level or even interruption of infusion of WR-2721. At 740 mg/m2 no grade 3 or 4 toxicities related to WR-2721 were observed, but two patients could not complete treatment because of TBI-induced prolonged thrombocytopenia following treatments 5 and 8. One patient completed all 10 treatments. At 910 mg/m2 of WR-2721, two patients requested removal from study because of malaise, one after 5 cycles and one after 7 cycles. One patient completed all 10 treatments.

• OSTI ID: 5514479
• Journal Information: International Journal of Radiation Oncology, Biology and Physics; (United States), Journal Name: International Journal of Radiation Oncology, Biology and Physics; (United States) Vol. 22:4; ISSN IOBPD; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

550600 -- Medicine
550603* -- Medicine-- External Radiation in Therapy-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANTINEOPLASTIC DRUGS
COMBINED THERAPY
DISEASES
DOSES
DRUGS
EXTERNAL IRRADIATION
IMMUNE SYSTEM DISEASES
IRRADIATION
LEUKEMIA
LYMPHOMAS
MAXIMUM PERMISSIBLE DOSE
NEOPLASMS
PATIENTS
RADIATION DOSES
SAFETY STANDARDS
STANDARDS
THERAPY
WHOLE-BODY IRRADIATION