Chronic daily administration of oral etoposide--a phase I trial.

In this phase I study, we administered etoposide (VP-16) orally for 21 consecutive days to patients with advanced refractory cancers. All patients had received previous chemotherapy, and 50% of patients had received more than one combination regimen. When given for 21 consecutive days, the maximum-tolerated dose of oral VP-16 was 50 mg/m2/d. Myelosuppression was the dose-limiting toxicity, and occurred between days 21 and 28. In most patients, blood counts had recovered sufficiently by day 35 to begin another 3-week course. WBC count nadirs of less than 1,000/microL occurred in four of 20 courses at this dose, and three patients required hospitalization for treatment of neutropenia and fever. Alopecia occurred in most patients; gastrointestinal (GI) and other toxicities were uncommon. Five of 16 patients with measurable tumor had partial responses of 3 to 4 months duration. Four of these five patients had malignancies that are usually unresponsive to VP-16 when administered by previously investigated schedules. This method of VP-16 administration is well tolerated, convenient, and may optimize antitumor efficacy by exploiting the schedule dependency of this drug. Phase II studies are necessary to define the level of activity of this schedule of VP-16.

Chronic daily administration of oral etoposide in refractory lymphoma.

In a phase II study, 25 patients with previously treated lymphoma received oral etoposide for 21 consecutive days. All patients were considered incurable with standard therapy. Etoposide was administered at 50 mg/m2 per day: courses were repeated every 28-35 days, depending on myelosuppression. 15 patients (60%) had partial responses (95% CI 41-77%), while 10 patients had no response. Median time to disease progression was 5 months (range 2-13 months). Oral etoposide was active against indolent and aggressive (intermediate and high grade) lymphomas; however, median time to progression was only 3 months in aggressive lymphoma compared with 8 months in indolent lymphoma. Myelosuppression was the major side-effect; 7 patients (28%) had a leucocyte nadir below 1000/microliters during the first course, and 11 patients required dose reduction during subsequent courses due to unacceptable leukopenia. All patients had total alopecia, but other side-effects were uncommon. These results highlight the importance of schedule in the administration of etoposide.

Choroid plexus papilloma with osseous and adipose metaplasia.

Rare cases of osseous and chondroid metaplasia in choroid plexus papillomas have been described. We report a case of left lateral ventricular choroid plexus papilloma presenting in a 25-year-old man. The tumor demonstrates prominent calcification with associated osseous metaplasia and a region of adipose metaplasia, which has not been previously described in these tumors. There is no evidence of mucin in the papilloma on mucicarmine and alcian blue stains. A MIB-1 labeling index (marker of cell proliferation) of 0.1% was noted. P53 immunoreactivity was not observed in the papilloma. Ann Diagn Pathol 5:43-47, 2001.