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.
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.
Prince
H Miles
HM
Hematology Service, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. Miles.Prince@petermac.org
Regester
Geoff
G
Gates
Priscilla
P
Jablonskis
Lina
L
Seymour
John F
JF
Lillie
Kate
K
West
Raelene
R
Wolf
Max
M
Januszewicz
Henry
H
Belford
David
D
D000328:Adult; D000368:Aged; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002330:Carmustine / Q000008:administration & dosage; D002417:Cattle; D045424:Complex Mixtures / Q000008:administration & dosage / Q000737:chemistry; D003561:Cytarabine / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D006133:Growth Substances / Q000008:administration & dosage*; D018380:Hematopoietic Stem Cell Transplantation; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000628:therapy; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D008892:Milk / Q000737:chemistry; D009061:Mouth Mucosa / Q000382:microbiology; D009067:Mouthwashes / Q000008:administration & dosage*; D011034:Podophyllotoxin / Q000008:administration & dosage; D013280:Stomatitis / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology
D000900:Anti-Bacterial Agents; D045424:Complex Mixtures; D006133:Growth Substances; D009067:Mouthwashes; D003561:Cytarabine; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine