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The present study investigated escalating doses of CA4P administered intravenously to patients with advanced cancer. <\/jats:p><jats:p> Patients and Methods: Patients with solid malignancies and good performance status received CA4P as a 10-minute infusion daily for 5 days repeated every 3 weeks. Pharmacokinetic sampling was performed during cycle 1. Patients receiving \u2265 52 mg\/m<jats:sup>2<\/jats:sup>\/d had serial dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) studies to measure changes in tumor perfusion with CA4P treatment. <\/jats:p><jats:p> Results: Thirty-seven patients received 133 treatment cycles. CA4P dose levels ranged from 6 mg\/m<jats:sup>2<\/jats:sup> to 75 mg\/m<jats:sup>2<\/jats:sup> daily. Severe pain at sites of known tumor was dose limiting at 75 mg\/m<jats:sup>2<\/jats:sup>. Dose-limiting cardiopulmonary toxicity (syncope and dyspnea or hypoxia) was noted as well in two patients treated at 75 mg\/m<jats:sup>2<\/jats:sup>. Other toxicities included hypotension, ataxia, dyspnea, nausea or vomiting, headache, and transient sensory neuropathy. Plasma CA4P and CA4 area under the concentration-time curve and maximal concentration values increased linearly with dose. Tumor perfusion, as measured by the first-order rate constant of gadolinium plasma to tissue transfer during DCE-MRI studies, was found to decrease in eight of 10 patients. Relationships were also demonstrated between perfusion changes and pharmacokinetic indices. A partial response was observed in a patient with metastatic soft tissue sarcoma, and 14 patients exhibited disease stability for a minimum of two cycles. <\/jats:p><jats:p> Conclusion: Doses of CA4P on a daily times five schedule of 52 to 65 mg\/m<jats:sup>2<\/jats:sup> were reasonably well-tolerated. The 52 mg\/m<jats:sup>2<\/jats:sup> dose is recommended for further study based on cumulative phase I experience with CA4P. Antitumor efficacy was observed, and the use of DCE-MRI provided a valuable noninvasive measure of the vascular effects of CA4P treatment. <\/jats:p>","DOI":"10.1200\/jco.2003.12.986","type":"journal-article","created":{"date-parts":[[2003,11,26]],"date-time":"2003-11-26T01:39:00Z","timestamp":1069810740000},"page":"4428-4438","source":"Crossref","is-referenced-by-count":260,"title":["Phase I Trial of the Antivascular Agent Combretastatin A4 Phosphate on a 5-Day Schedule to Patients With Cancer: Magnetic Resonance Imaging Evidence for Altered Tumor Blood Flow"],"prefix":"10.1200","volume":"21","author":[{"given":"James P.","family":"Stevenson","sequence":"first","affiliation":[{"name":"From the University of Pennsylvania Cancer Center, Philadelphia, PA; Mary Babb Randolph Cancer Center, Morgantown, WV; Oxigene Inc, Boston, MA; and Gray Cancer Center, Norwood, United Kingdom."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Rosen","sequence":"additional","affiliation":[{"name":"From the University of Pennsylvania Cancer Center, Philadelphia, PA; 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