Clinical study of a new antimetastatic compound, Nafazatrom (Bay g 6575): Effects on platelet consumption and monocyte prostaglandin production in patients with advanced cancer Journal Article
| Authors: | Warrell, R. P. Jr; Bockman, R. S.; Staszewski, H.; Maiese, K. |
| Article Title: | Clinical study of a new antimetastatic compound, Nafazatrom (Bay g 6575): Effects on platelet consumption and monocyte prostaglandin production in patients with advanced cancer |
| Abstract: | Nafazatrom (Miles Laboratories, West Haven, CT) is a potent inhibitor of metastasis in several animal model systems. The compound is active whether cancer cells are injected intravenously or are allowed to spontaneously metastasize from established tumors. Before studying the antimetastatic effects of Nafazatrom in a long‐term randomized clinical trial, the authors conducted a preliminary study to evaluate its toxicity as well as its effects on certain parameters hat have been associated with the biology of metastasis. Since the interaction of platelets, monocytes, and tumor cells may be important for metastasis formation, the authors serially evaluated plasma levels of factors secreted from activated platelets (beta‐thromboglobulin and platelet factor 4) that are inversely correlated with platelet survival. Products of arachidonate metabolism from monocytes were also measured since Nafazatrom is known to modulate prostaglandin production. Thirty‐one patients received doses of Nafazatrom ranging from 75 to 1500 mg/m2 orally three times a day. The dose was escalated every 2 weeks. There was no toxicity at any dose level. No major antitumor responses were observed. There was no consistent change in levels of platelet factors either within individual patients or for the population as a whole. Although Nafazatrom (20 μM) decreased tritiated arachidonate incorporation into peripheral blood monocytes from normal subjects in vitro, this effect was not seen in patients treated with the drug. Release of 3PGE2 and 3HETE from cultured monocytes was also not altered by treatment with Nafazatrom. It was concluded that Nafazatrom is safe and well‐tolerated up to total doses of 4500 mg/day. The data suggest that the antimetastatic activity of Nafazatrom in vivo is mediated by mechanisms other than by a decrease in platelet consumption or by modulation of arachidonate metabolism by monocytes. Cancer 57:1455–1460, 1986. Copyright © 1986 American Cancer Society |
| Keywords: | adult; cancer chemotherapy; clinical article; aged; human cell; drug efficacy; antineoplastic agents; cells, cultured; metastasis; lung neoplasms; pyrazoles; prostaglandin; drug toxicity; phase 1 clinical trial; radioisotope; monocyte; monocytes; drug therapy; macrophages; arachidonic acid; prostaglandins e; therapy; oral drug administration; thrombocyte function; blood platelets; middle age; drug evaluation; intoxication; thrombocyte factor 4; new drug; cancer; human; male; female; priority journal; support, non-u.s. gov't; platelet factor 4; blood and hemopoietic system; beta-thromboglobulin; beta thromboglobulin; nafazatrom; arachidonic acid h 3; prostaglandin e2 h 3 |
| Journal Title: | Cancer |
| Volume: | 57 |
| Issue: | 8 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 1986-04-15 |
| Start Page: | 1455 |
| End Page: | 1460 |
| Language: | English |
| DOI: | 10.1002/1097-0142(19860415)57:8<1455::Aid-cncr2820570803>3.0.Co;2-j |
| PUBMED: | 2936443 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 18 August 2021 -- Source: Scopus |
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