A Phase Ib Clinical Trial of PV701, a Milk-Derived Protein Extract, for the Prevention and Treatment of Oral Mucositis in Patients Undergoing High-Dose BEAM Chemotherapy

Abstract

Despite the best available agents to prevent mucositis, most patients receiving high-dose chemoradiotherapy regimens experience severe mucositis, and new therapies are needed. In this study, we evaluated the safety and tolerability of a milk-derived growth factor extract (PV701 mouthwash) intended to prevent oral mucositis (OM) after carmustine, etoposide, cytosine arabinoside, and melphalan (BEAM) chemotherapy. PV701 mouthwash (15 mL x 13.5 mg/mL) was administered 6 times a day for 12 days, from day--6 to day +5, to patients with lymphoma, who were given BEAM on day--6 to day--2, with autologous stem cells infused on day 0. Dose de-escalation of PV701 was planned if dose-limiting toxicities occurred. The severity and duration of OM, the duration of enteral/parenteral feeding, the requirement for intravenous opiates, and admission to intensive care were recorded. Outcomes were also compared with those of historical control patients. Nine patients received PV701 13.5 mg/mL. PV701 was well tolerated, and no dose-limiting toxicities were observed. Compared with 89 historical controls, the 9 PV701-treated patients had significantly less frequent grade 2 or 3 OM ( P=.0006) and had grade>or=3 OM for an estimated 5 fewer days ( P=.0003). There was a reduction in the need for enteral/parenteral feeding ( P=.012), its duration ( P=.010), and its frequency ( P=.022) and in the duration of intravenous opiates ( P=.0006). We conclude that PV701 mouthwash is readily administered with minimal side effects at a dose of 1215 mg/d, and further investigation of this agent is warranted.

The role of alternative and natural agents, cryotherapy, and/or laser for management of alimentary mucositis

“…The most common problems encountered by the authors included single studies with not enough power, lack of adequate controls, and lack of investigator or patient blinding. The review of selected studies on alternate/ natural agents revealed small clinical trials that evaluated vitamins A [14], E [11,22,29], B 12 [7], folate and diet supplement [1,7], glutamine [3,4,20] aloe vera [27], PV701 (milk-derived protein extract) [21], and one preclinical study of the effect of curcumin (plant extract) associated with vitamin E in rats [22]. In general, results of these studies were conflicting and had insufficient evidence to allow for a guideline.…”

Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients

“…TGF-β mouthwashes or enriched food were not effective to reduce oral mucositis in the used formulations [80][81][82]. A mouthwash with bovine milk-derived whey growth factors (PV-701) was well tolerated, and as compared to historical controls, the severity as well as the duration of oral mucositis seemed to be decreased in autologous HSCT recipients [83]. With respect to the use of topical EGF, the panel expressed concerns about the potential unfavorable effects of this growth factor on tumor growth [84][85][86], whereas the use of subcutaneous IL-11 was associated with severe side effects and mortality [87].…”

Emerging approaches for prophylaxis and management of oropharyngeal mucositis in cancer therapy

“…Animal mucositis models have shown effect, leading to a Phase Ib clinical trial in nine patients undergoing BEAM (BCNU, etoposide, cytosine arabinoside and melphalan) chemotherapy and compared with historical controls [150]. The results suggested that the severity and duration of oral mucositis was reduced, and reduction in the need for parenteral feeding and use of opiates was seen.…”

“…Mucotrol is a topical mouth rinse, made up of milk-derived proteins, that includes a number of growth factors: TGF-β, platelet-derived growth factor, insulin-like growth factor, FGFs and bacteriostatic proteins [150]. Animal mucositis models have shown effect, leading to a Phase Ib clinical trial in nine patients undergoing BEAM (BCNU, etoposide, cytosine arabinoside and melphalan) chemotherapy and compared with historical controls [150].…”