Phase I study of MVE-2 therapy in human cancer

A. Rios; M. Rosenblum; M. Powell; E. Hersh

Phase I study of MVE-2 therapy in human cancer

A. Rios, M. Rosenblum, M. Powell, E. Hersh

Cancer Center

Research output: Contribution to journal › Article › peer-review

Original language	English (US)
Pages (from-to)	C-146
Journal	Proceedings of the American Society of Clinical Oncology
Volume	Vol. 1
State	Published - 1982

ASJC Scopus subject areas

General Medicine

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@article{a91d683a6c84419a968a92b8b92d27e2,

title = "Phase I study of MVE-2 therapy in human cancer",

author = "A. Rios and M. Rosenblum and M. Powell and E. Hersh",

note = "Funding Information: M. Rosenblum, A. Rios, E. Hersh and T. Loo. The University of Texas System Cancer Center, M.D. Anderson Hospital, Houston, Tx. 77030 MVE-2 is a polyanlonic macromolecule with an average molecular weight of 15,500 daltons. In concert with its phase I clinical trial, we developed a high performance liquid chro-matographlc (HPLC) method for analysis of MVE-2 in biological fluids to study its pharmacokinetics. The lowest limits of detection of MVE-2 were lO~g/ml in plasma and 25~g/ml in urine. Pharmacology studies were performed on six patients with cancer who received MVE-2 as a l-hour infusion. Four patients received 650 mg/m 2 and 2 received 1000 mg/m 2 and 1500 mg/m 2 respectively. MVE-2 disappeared from the plasma exponentially and its pharmacoklnetics could best (r2-0.95) be described by the open one compartment mathemai-cal model. Plasma t½ ranged from 13-15 minutes and was independent of dose. The apparent volume distribution (Vd) was 220 ml/kp and the clearance rate was II.I ml/mln/kg. Although the agent was cleared rapidly, only 45Z of the dose was excreted in the urine 24 hours after administration with only small amounts of MVE-2 excreted in urine thereafter. In light of the fast clearance but relatively low urinary excretion of this agen~ these studies suggest that MVE-2 may be rapidly sequestered or metabolized in vlvo. Supported by NCI contract 6Rd-87185, Grant CA-29769, Biomedical Research Support Grant RR 5511 and a grant from Adria Laboratories. Funding Information: MVE-2 a polymer of malelc anhydride and dlvlnyl ether, molecular weight 15,500 modifies host defenses and has antltumor activity in animals. 57 patients (12 with hematological malignancies and 45 with solid tumors) were treated and evaluated for toxicity and host defense parameters. The schedules of administration were: Weekly 25-650 mg/m ~ (32 pts); every-other-week 500-1200 mg/m 2 (19 pts); every-three-weeks 1200-1500 mg/m 2 (6 pts). No cardiac, pulmonary or hematological toxlcltles were observed. Proteinurla occurred in 24 patients treated with 500 mg/m 2 or more. It was reversible and was composed of 80% albumin and 20% globulin. BUN and serum creatlnine were normal and nephrotlc syndrome did not occur. The median pre, day 7 and day 21 value for host defense parameters were: Adherent monocyte macrophages in the peripheral blood: 6.3, 4.98 and 4.08 cells/ml blood x 104 , serum lysozyme 7.8, 9.9 and I0.I ug/ml, antlbody-dependent cellular cytotoxicity (ADCC) to chicken erythrocytes: 13.6, 17 and 20.9% target cell lysls (TCL), ADCC to human erythrocytes 7.0, 10.2, and 8.5% TCL, ADCC to the CEM human leukemia cell lines: 49.2, 54.7, and 52.7% TCL, and natural killer cell activity to the K562 cell line: 17.2, 21.3 and 20.8% TCL. Further studies of the proteinurla caused by MVE-2 are indicated. Supported by NCI Grant CA-29769 and Adria Laboratories. * Deceased.",

year = "1982",

language = "English (US)",

volume = "Vol. 1",

pages = "C--146",

journal = "Proceedings of the American Society of Clinical Oncology",

}

TY - JOUR

T1 - Phase I study of MVE-2 therapy in human cancer

AU - Rios, A.

AU - Rosenblum, M.

AU - Powell, M.

AU - Hersh, E.

N1 - Funding Information: M. Rosenblum, A. Rios, E. Hersh and T. Loo. The University of Texas System Cancer Center, M.D. Anderson Hospital, Houston, Tx. 77030 MVE-2 is a polyanlonic macromolecule with an average molecular weight of 15,500 daltons. In concert with its phase I clinical trial, we developed a high performance liquid chro-matographlc (HPLC) method for analysis of MVE-2 in biological fluids to study its pharmacokinetics. The lowest limits of detection of MVE-2 were lO~g/ml in plasma and 25~g/ml in urine. Pharmacology studies were performed on six patients with cancer who received MVE-2 as a l-hour infusion. Four patients received 650 mg/m 2 and 2 received 1000 mg/m 2 and 1500 mg/m 2 respectively. MVE-2 disappeared from the plasma exponentially and its pharmacoklnetics could best (r2-0.95) be described by the open one compartment mathemai-cal model. Plasma t½ ranged from 13-15 minutes and was independent of dose. The apparent volume distribution (Vd) was 220 ml/kp and the clearance rate was II.I ml/mln/kg. Although the agent was cleared rapidly, only 45Z of the dose was excreted in the urine 24 hours after administration with only small amounts of MVE-2 excreted in urine thereafter. In light of the fast clearance but relatively low urinary excretion of this agen~ these studies suggest that MVE-2 may be rapidly sequestered or metabolized in vlvo. Supported by NCI contract 6Rd-87185, Grant CA-29769, Biomedical Research Support Grant RR 5511 and a grant from Adria Laboratories. Funding Information: MVE-2 a polymer of malelc anhydride and dlvlnyl ether, molecular weight 15,500 modifies host defenses and has antltumor activity in animals. 57 patients (12 with hematological malignancies and 45 with solid tumors) were treated and evaluated for toxicity and host defense parameters. The schedules of administration were: Weekly 25-650 mg/m ~ (32 pts); every-other-week 500-1200 mg/m 2 (19 pts); every-three-weeks 1200-1500 mg/m 2 (6 pts). No cardiac, pulmonary or hematological toxlcltles were observed. Proteinurla occurred in 24 patients treated with 500 mg/m 2 or more. It was reversible and was composed of 80% albumin and 20% globulin. BUN and serum creatlnine were normal and nephrotlc syndrome did not occur. The median pre, day 7 and day 21 value for host defense parameters were: Adherent monocyte macrophages in the peripheral blood: 6.3, 4.98 and 4.08 cells/ml blood x 104 , serum lysozyme 7.8, 9.9 and I0.I ug/ml, antlbody-dependent cellular cytotoxicity (ADCC) to chicken erythrocytes: 13.6, 17 and 20.9% target cell lysls (TCL), ADCC to human erythrocytes 7.0, 10.2, and 8.5% TCL, ADCC to the CEM human leukemia cell lines: 49.2, 54.7, and 52.7% TCL, and natural killer cell activity to the K562 cell line: 17.2, 21.3 and 20.8% TCL. Further studies of the proteinurla caused by MVE-2 are indicated. Supported by NCI Grant CA-29769 and Adria Laboratories. * Deceased.

PY - 1982

Y1 - 1982

UR - http://www.scopus.com/inward/record.url?scp=0020451369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0020451369&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:0020451369

VL - Vol. 1

SP - C-146

JO - Proceedings of the American Society of Clinical Oncology

JF - Proceedings of the American Society of Clinical Oncology

ER -

Phase I study of MVE-2 therapy in human cancer

ASJC Scopus subject areas

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