This Article Full Text 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 Herbst, R. S. Articles by Schiller, J. H. Search for Related Content PubMed PubMed Citation Articles by Herbst, R. S. Articles by Schiller, J. H.

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 Cancer¹

Department of Thoracic/Head and Neck Medical Oncology and Biostatistics, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030 [R. S. H., H. T. T., B. N. B., V. A.]; Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, Texas 78229 [L. A. H.]; Vanderbilt University, Nashville, Tennessee 37232 [D. P. C.]; Genaera Corporation, Plymouth Meeting, Pennsylvania 19462 [K. J. H., A. D., J. I. W., H. H., S. S.]; and The Department of Medicine, The University of Wisconsin, Madison, Wisconsin 53792 [J. H. S.]

Purpose: Squalamine is an antitumor agent that has been shown to have antiangiogenic activity in animal models. This Phase I/IIA study was designed to assess the safety, clinical response, and pharmacokinetics of squalamine when administered as a 5-day continuous infusion in conjunction with standard chemotherapy every 3 weeks in patients with stage IIIB (pleural effusion) or stage IV non-small cell lung cancer.

Experimental Design: Patients with chemotherapy-naive non-small cell lung cancer were treated with escalating doses of squalamine in combination with standard doses of paclitaxel and carboplatin. Paclitaxel and carboplatin were administered on day 1, followed by squalamine as a continuous infusion on days 1–5, every 21 days.

Results: A total of 45 patients were enrolled (18 patients in the Phase I dose escalation arm and 27 in the Phase IIA arm). The starting dose of squalamine was 100 mg/m²/day and escalated to 400 mg/m²/day; two of three patients at 400 mg/m²/day had dose-limiting toxicity that included grade 3/4 arthralgia, myalgia, and neutropenia. On the basis of safety and toxicity, 300 mg/m²/day was selected as the Phase II dose of squalamine in this combination regimen. An additional 27 patients (a total of 33) were enrolled according to the protocol treatment schema at 300 mg/m²/day. There was no pharmacokinetic evidence of drug interactions for the combination of squalamine, carboplatin, and paclitaxel. Forty-three patients were evaluable for response. Partial tumor responses were observed in 12 (28%) of these patients; an additional 8 evaluable patients (19%) were reported to have stable disease. For all of the patients treated, the median survival was 10.0 months; and 1-year survival was 40%.

Conclusions: The combination of squalamine given continuously daily for 5 days, with paclitaxel and carboplatin given on day 1, is well tolerated. Patient survival data and the safety profile of this drug combination suggests that the use of squalamine given at its maximum tolerated dose with cytotoxic chemotherapy should be explored further as a potentially effective therapeutic strategy for patients with stage IIIB or IV non-small cell lung cancer.

This article has been cited by other articles:

				C. J. Walsh, C. A. Luer, A.B. Bodine, C. A. Smith, H. L. Cox, D. R. Noyes, and M. Gasparetto Elasmobranch immune cells as a source of novel tumor cell inhibitors: Implications for public health Integr. Comp. Biol., December 1, 2006; 46(6): 1072 - 1081. [Abstract] [Full Text] [PDF]

				D. R. Yance Jr and S. M. Sagar Targeting Angiogenesis With Integrative Cancer Therapies Integr Cancer Ther, March 1, 2006; 5(1): 9 - 29. [Abstract] [PDF]

				M. N. Chernova, D. H. Vandorpe, J. S. Clark, J. I. Williams, M. A. Zasloff, L. Jiang, and S. L. Alper Apparent receptor-mediated activation of Ca2+-dependent conductive Cl- transport by shark-derived polyaminosterols Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2005; 289(6): R1644 - R1658. [Abstract] [Full Text] [PDF]

				R. J. Pietras and O. K. Weinberg Antiangiogenic Steroids in Human Cancer Therapy Evid. Based Complement. Altern. Med., March 1, 2005; 2(1): 49 - 57. [Abstract] [Full Text] [PDF]

				P. A. Kyzas, I. W. Cunha, and J. P.A. Ioannidis Prognostic Significance of Vascular Endothelial Growth Factor Immunohistochemical Expression in Head and Neck Squamous Cell Carcinoma: A Meta-Analysis Clin. Cancer Res., February 15, 2005; 11(4): 1434 - 1440. [Abstract] [Full Text] [PDF]