Propantheline protects the oral mucosa after high-dose ifosfamide, carboplatin, etoposide and autologous stem cell transplantation.
Oral mucositis is a dose-limiting toxicity of high-dose etoposide regimens. Since etoposide is excreted in saliva, we tested the hypothesis that the induction of xerostomia would reduce the severity of the mucositis. We designed a phase II trial of propantheline in patients receiving high-dose ICE (ifosfamide 20 mg/m2, carboplatin 1.8 g/m2, etoposide 3 g/m2 in divided doses over 6 days) chemotherapy plus autologous hematopoietic stem cell support. We treated 31 consecutive patients and graded the oral mucositis according to WHO criteria. Mild (WHO grade 0, I, II) mucositis occurred in 28 of 31 (90%) (95% CI 74-98%) patients; severe (WHO grade III, IV) mucositis occurred in three of 31 patients (10%) (95% CI 2-25%) patients. In contrast, a published reference group treated with the same doses and schedule of ICE reported mild mucositis in 10 of 46 (22%) (95% CI 11-36%) patients and severe mucositis in 36 of 46 (78%) (95% CI 64-89%). Propantheline therapy had no protective effect on esophagitis and enteritis associated with high-dose ICE. Minor toxicities were constipation and asymptomatic tachycardia; major toxicities were palpitations in one patient and urinary retention in one patient. We conclude that anticholinergic therapy dramatically reduced the oral mucositis associated with high-dose etoposide and should be considered as a supportive care measure for patients receiving etoposide-containing regimens.
Oblon
D J
DJ
Roger Williams Medical Center, Department of Medicine, Brown University School of Medicine, Providence, Rhode Island 02908, USA.
Paul
S R
SR
Oblon
M B
MB
Malik
S
S
D000328:Adult; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use; D016190:Carboplatin / Q000008:administration & dosage / Q000009:adverse effects; D018680:Cholinergic Antagonists / Q000008:administration & dosage / Q000627:therapeutic use*; D005047:Etoposide / Q000008:administration & dosage / Q000009:adverse effects; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D011413:Propantheline / Q000008:administration & dosage / Q000627:therapeutic use*; D013280:Stomatitis / Q000139:chemically induced* / Q000517:prevention & control*; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous
D000897:Anti-Ulcer Agents; D018680:Cholinergic Antagonists; D011413:Propantheline; D005047:Etoposide; D016190:Carboplatin; D007069:Ifosfamide