This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Motzer, R. J. Articles by Bosl, G. J. Search for Related Content PubMed PubMed Citation Articles by Motzer, R. J. Articles by Bosl, G. J.

Phase II Trial of Suramin in Patients with Advanced Renal Cell Carcinoma: Treatment Results, Pharmacokinetics, and Tumor Growth Factor Expression¹

Genitourinary Oncology Service, Division of Solid Tumor Oncology, Department of Medicine [R. J. M., D. M. N., H. I. S., D. F. B., C. L., G. J. B.], Laboratory of Mammalian Cell Transformation [D. M. N., A. P. A.], Department of Radiology [P. O.], Department of Pathology [V. R.], Program of Molecular Pharmacology and Therapeutics [W. P. T.], and Division of Pharmacy Services [J. I.], Memorial Sloan-Kettering Cancer Center and the Department of Medicine [R. J. M., D. M. N., H. I. S., D. F. B., G. J. B.], Cornell University Medical College, New York, New York 10021

Twenty-six patients with advanced renal cell carcinoma were treated with suramin administered by continuous infusion, with dosing determined by a nomogram. One patient achieved a partial response and five patients achieved a minor response or had stable disease for > 3 months. Toxicities included an immune-mediated thrombocytopenia in one patient and Staphylococcus sepsis that was not associated with neutropenia in five patients. Pharmacokinetic parameters were determined by the ADAPT II MAP-Bayesian parameter estimation program. Patient data were fit using a two-compartment open model and first-order rate elimination. This showed a wide interpatient variation in time to target level (median, 13.8 days), volume of distribution (median, 15.2 liters/m²), and t_1/2-ß (median, 20.6 days). The patients who achieved a partial response, minor response, or stable disease had a slower elimination rate of suramin, compared to patients with progressive disease. Tumor specimens were obtained prior to therapy and were analyzed for the production of five different growth factor-specific RNA transcripts. These included transforming growth factor , acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor types A and B. No difference in the pattern of growth factor expression was seen in tumors of responding and nonresponding patients. Suramin does not have significant antitumor activity in renal cell carcinoma. The wide variability in pharmacokinetics suggests that individual dosing should be used in future trials of suramin for treatment for other malignancies. Pertinent corollary studies of tumor biology and clinical pharmacology should be included whenever possible in clinical trials in patients with renal cell carcinoma.

¹ Supported in part by NIH Grants CM-57732 and CA-05826 and a National Kidney Foundation Young Investigator Award (D. M. N.). R. J. M. and D. M. N. are recipients of an American Cancer Society Career Development Award.

² To whom requests for reprints should be addressed, at Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021.

Received 5/14/92. Accepted 8/ 7/92.

This article has been cited by other articles:

				R. J. Motzer, J. Bacik, L. H. Schwartz, V. Reuter, P. Russo, S. Marion, and M. Mazumdar Prognostic Factors for Survival in Previously Treated Patients With Metastatic Renal Cell Carcinoma J. Clin. Oncol., February 1, 2004; 22(3): 454 - 463. [Abstract] [Full Text] [PDF]

				R. J. Motzer, J. Bacik, T. Mariani, P. Russo, M. Mazumdar, and V. Reuter Treatment Outcome and Survival Associated With Metastatic Renal Cell Carcinoma of Non-Clear-Cell Histology J. Clin. Oncol., May 1, 2002; 20(9): 2376 - 2381. [Abstract] [Full Text] [PDF]

				R. J. Motzer, M. Mazumdar, J. Bacik, P. Russo, W. J. Berg, and E. M. Metz Effect of Cytokine Therapy on Survival for Patients With Advanced Renal Cell Carcinoma J. Clin. Oncol., May 9, 2000; 18(9): 1928 - 1935. [Abstract] [Full Text] [PDF]

				R. J. Motzer, M. Mazumdar, J. Bacik, W. Berg, A. Amsterdam, and J. Ferrara Survival and Prognostic Stratification of 670 Patients With Advanced Renal Cell Carcinoma J. Clin. Oncol., August 1, 1999; 17(8): 2530 - 2530. [Abstract] [Full Text] [PDF]

				A Levitzki and A Gazit Tyrosine kinase inhibition: an approach to drug development Science, March 24, 1995; 267(5205): 1782 - 1788. [Abstract] [PDF]