A Phase I/IIA Trial of Continuous Five-Day Infusion of Squalamine Lactate (MSI-1256F) Plus Carboplatin and Paclitaxel in Patients with Advanced Non-Small Cell Lung Cancer

摘要: Purpose: Squalamine is an antitumor agent that has been shown to have antiangiogenic activity in animal models. This Phase I/IIA study was designed assess the safety, clinical response, and pharmacokinetics of squalamine when administered as a 5-day continuous infusion conjunction with standard chemotherapy every 3 weeks patients stage IIIB (pleural effusion) or IV non-small cell lung cancer. Experimental Design: Patients chemotherapy-naive cancer were treated escalating doses combination paclitaxel carboplatin. Paclitaxel carboplatin on day 1, followed by days 1–5, 21 days. Results: A total 45 enrolled (18 I dose escalation arm 27 IIA arm). The starting 100 mg/m 2 /day escalated 400 /day; two three at had dose-limiting toxicity included grade 3/4 arthralgia, myalgia, neutropenia. On basis safety toxicity, 300 selected II this regimen. An additional (a 33) according protocol treatment schema /day. There no pharmacokinetic evidence drug interactions for squalamine, carboplatin, paclitaxel. Forty-three evaluable response. Partial tumor responses observed 12 (28%) these patients; 8 (19%) reported stable disease. For all treated, median survival 10.0 months; 1-year 40%. Conclusions: given continuously daily 5 days, well tolerated. Patient data profile suggests use its maximum tolerated cytotoxic should be explored further potentially effective therapeutic strategy