Human / Clinical Studies
In 2001, a phase II trial (AETERNA-AE-MM-00-02) of AE-941/Neovastat was initiated in patients with relapsed or refractory multiple myeloma. This trial closed approximately 1 year later, and no results have been reported.
Two randomized phase III trials of AE-941/Neovastat in patients with advanced cancer have been approved by the U.S. Food and Drug Administration (FDA). In one trial (MDA-ID-99303), which is completed, treatment with oral AE-941/Neovastat plus chemotherapy and radiation therapy was compared with treatment with placebo plus the same chemotherapy and radiation therapy in patients with stage III NSCLC. In the second trial, which closed to patient recruitment in 2002, treatment with oral AE-941/Neovastat was compared with treatment with placebo in patients with metastatic renal cell carcinoma. Results from this second phase III trial have not been reported in the peer-reviewed scientific literature. Despite AE-941/Neovastat being granted orphan drug status by the FDA in 2002 for use in the treatment of renal cell carcinoma, the company that produces AE-941/Neovastat, Aeterna Laboratories, announced in early 2004 that this application would be discontinued in favor of a focus on the treatment of NSCLC.[20,21]
In 2010, the results of a randomized, double-blind, placebo-controlled phase III trial aimed at assessing the effect of adding AE-941 to chemotherapy and radiation therapy on the overall survival of patients with nonresectable stage III NSCLC were reported. A total of 379 eligible patients received induction chemotherapy followed by concurrent chemotherapy with chest radiation therapy; participating centers used one of two chemotherapy regimens, either carboplatin and paclitaxel, or cisplatin and vinorelbine. No statistically significant difference in overall survival was observed between the group (n = 188) receiving chemotherapy and radiation therapy plus AE-941 (120 mL administered orally twice daily) and the group receiving chemotherapy and radiation therapy plus placebo (n = 191). Both AE-941 and placebo were well tolerated.
Cartilage Use in Cancer Treatment: Clinical Studies With Therapeutic Endpointsa,b
No. = number; NSCLC = non-small cell lung cancer; wk = week.
a See text and the NCI Dictionary of Cancer Terms for additional information and definition of terms.
b Other clinical studies have been conducted, but no results have been reported.
c Strongest evidence reported that the treatment under study has anticancer activity or otherwise improves the well-being of cancer patients.
d Chemotherapy, radiation therapy, hormonal therapy, or cytokine therapy given/allowed at the same time as cartilage therapy.
e For information about Levels of Evidence analysis and an explanation of the level of evidence scores, see Levels of Evidence for Human Studies of Cancer Complementary and Alternative Medicine.
f Study results reported in review article or abstract form only; insufficient information presented for Level of Evidence analysis.
g Insufficient information available to describe these studies separately.
|Reference Citation(s) ||Type of Study ||Type(s) of Cancer||Cartilage Product (Source)||No. of Patients: Treated; Control||Strongest Benefit Reportedc||Concurrent Therapyd||Level of Evidence Scoree|
||| Nonconsecutive case series||Various advanced or recurrent ||Catrix (bovine)||31; None||Complete response, 19 patients ||Yes ||3iiiDiii |
|||Phase II trial ||Various metastatic ||Catrix (bovine)||9; None||Complete response, 1 patient, metastatic renal cell carcinoma ||No ||3iiiDiii |
|||Phase II trial ||Metastatic renal cell ||Catrix (bovine)||35; None||Partial response, 3 of 22 evaluable patients||Unknown||Nonef|
|[10,17]||Two phase I/II trialsg||Various advanced, refractory solid tumors||AE-941/ Neovastat (shark) ||331; None ||Improved survival, higher versus lower doses, patients with stage III/IV non-small cell lung cancer (unplanned retrospective analysis), and patients with refractory renal cell carcinoma (prospective analysis)||Unknown||Nonef|
|||Phase I/II trial||Advanced non-small cell lung cancer ||AT-941/Neovastat (shark) ||80; None ||No dose-limiting toxicity found. Improved survival time in patients receiving the highest doses when survival analysis was conducted, and stable disease for greater number of patients receiving higher doses. No tumor response observed.||Yes or refused standard therapy||None|
|||Phase I/II trial ||Various advanced solid tumors||Cartilade (shark)||60; None ||Stable disease for 12 wk or more, 10 of 50 evaluable patients||No ||3iiiDiii|
|||Phase II trial||Metastatic, refractory breast ||Unknown (shark) ||20; None ||Stable disease for 8 wk or more, 2 of 10 evaluable patients ||No ||Nonef|
|||Phase II trial ||Metastatic, hormone- refractory prostate||Unknown (shark)||12; None ||Stable disease for 20 wk or more, 3 of 10 evaluable patients ||No ||Nonef|
|||Phase II trial ||Various advanced brain ||BeneFin (shark) ||12; None ||Stable disease for 20 wk or more, 2 of 10 evaluable patients||No ||Nonef|
|||Phase III randomized, placebo-controlled, double-blind trial (2 arms)||Breast and colorectal||BeneFin (shark)||42; 41||No statistically significant difference||No||1i|
|||Randomized controlled phase III trial||NSCLC||AE-941 (shark)||188; 191||None||Cisplatin and vinorelbine; carboplatin and paclitaxel||1iA|
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- Lu C, Lee JJ, Komaki R, et al.: Chemoradiotherapy with or without AE-941 in stage III non-small cell lung cancer: a randomized phase III trial. J Natl Cancer Inst 102 (12): 859-65, 2010.