Phase I trials of WR2721 in combination with radiation therapy and with the alkylating agents cyclophosphamide and cis-platinum

Journal Article · · Cancer Clin. Trials; (United States)

DOI:https://doi.org/10.1016/0360-3016(81)90259-5· OSTI ID:5449735

Kligerman, M M; Blumberg, A L; Glick, J H; Nelson, D F; Glover, D; Yuhas, J M; Amols, H I; Goodman, R L

Three phase I trials of the radioprotector S-2-(3-aminopropylamino) ethylphosphorothioic acid (WR2721) have accessed 60 patients. Study 1 is devised to determine the maximum tolerated dose (MTD) of a single dose of the protector 15 to 30 minutes before a single radiation treatment of a size used routinely in palliative management. Study 2 plans to determine the MTD for up to 15 daily doses of the drug over 3 weeks during palliative radiotherapy. Also, the multipe-dose study will establish the MTD before palliative irradiation for fewer than five fractions a week. Study 3 uses the existing single-dose MTD determined in Study 1 as pretreatment 15 to 30 minutes before cyclophosphamide or cis-platinum. Toxic symptoms include emesis, hypotension, hypertension, somnolence, and sneezing. Only one serious episode of hypotension, considered idiosyncratic, and one instance of moderate to severe vomiting have occurred. Forty-one patients have been entered in Study 1 and a dose of 600 mg/m2 has been reached. The next step is to proceed to the planned highest level of 740 mg/m2. Of five patients in the multiple-dose study, one has been given, without toxicity, WR2721 at the level of 100 mg/m2 for 15 fractions over 3 weeks. Fourteen patients are accessed to the alkylating agent study. Using protector doses of 450 mg/m2, a cyclophosphamide level of 1500 mg/m2 has been accomplished. However, two of three patients who received 450 mg/m2 of WR2721 before 120 mg/m2 of cis-platinum have shown moderate elevation of the serum creatinine, both of which returned to normal.

• Research Organization: Department of Radiation Therapy, Hospital of the University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
• OSTI ID: 5449735
• Journal Information: Cancer Clin. Trials; (United States), Journal Name: Cancer Clin. Trials; (United States) Vol. 4:4; ISSN CCTRD
• Country of Publication: United States
• Language: English

Related Subjects

550603* -- Medicine-- External Radiation in Therapy-- (1980-)
560151 -- Radiation Effects on Animals-- Man
62 RADIOLOGY AND NUCLEAR MEDICINE
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ALKYLATING AGENTS
CARDIOVASCULAR DISEASES
CHEMOTHERAPY
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DOSES
DRUGS
ENDOXAN
FRACTIONATED IRRADIATION
HYPERTENSION
HYPOTENSION
IMMUNOSUPPRESSIVE DRUGS
IRRADIATION
PATIENTS
PLATINUM COMPOUNDS
RADIATION DOSES
RADIOPROTECTIVE SUBSTANCES
RADIOSENSITIVITY EFFECTS
SIDE EFFECTS
SYMPTOMS
THERAPY
TRANSITION ELEMENT COMPOUNDS
VASCULAR DISEASES
VOMITING