The genetics of the Lp Antigen

Several genetic models were considered to explain the distribution of qualitatively positive and negative children in 204 Caucasian families. A model which best describes the inheritance of the Lp antigenic expression involves a major genetic locus which distinguishes two overlapping continuously distributed modes of quantitative activity.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/66139/1/j.1469-1809.1974.tb01992.x.pd

Phase I/II study of oral etoposide plus GM-CSF as second-line chemotherapy in platinum-pretreated patients with advanced ovarian cancer

The aim of this phase I/II study was to determine the maximum tolerated dose (MTD) and the dose-limiting toxicities of chronic oral etoposide given on days 1–10 followed by rescue with subcutaneous (s.c.) granulocyte-macrophage colony-stimulating factor (GM-CSF) on days 12–19 as second-line chemotherapy in platinum-pretreated patients (pts) with advanced ovarian carcinoma. Cohorts of three to six pts were treated with doses of oral etoposide from 750 mg m−2 cycle−1 escalated to 1250 mg m−2 cycle−1 over 10 days, every 3 weeks. Subcutanous GM-CSF, 400 μg once daily, days 12–19, was added if dose-limiting granulocytopenia was encountered. In total, 18 pts with a median Karnofsky index of 80% (range, 70–100%) and a median time elapsed since the last platinum dose of 10 months (range, 1–24 months), 30% of whom showed visceral metastases, were treated at four dose levels (DLs) of oral etoposide on days 1–10 of each cycle as follows: DL 1, 750 mg m−2 cycle−1, without GM-CSF, three pts; DL 2, 1000 mg m−2 cycle−1, without GM-CSF, three pts; DL 3, 1000 mg m−2 cycle−1, with GM-CSF, six pts; and DL 4, 1250 mg m−2 cycle−1, with GM-CSF, six pts. All pts were assessable for toxicity and 16 pts for response. Dose-limiting toxicity (DLT) was reached at DL 4 by three of six pts, showing World Health Organization (WHO) toxicity grade 4. One patient died from gram-negative sepsis associated with granulocytopenia grade 4. Two more pts developed uncomplicated granulocytopenia grade 4. Thus, we recommend that DL 3 can be used for further phase II evaluation (i.e. oral etoposide 1000 mg m−2 cycle−1, days 1–10, followed by s.c. GM-CSF 400 μg, days 12–19). The clinical complete or partial responses in each patient cohort were: DL 1, one of three pts; DL 2, one of three pts; DL 3, three of five pts; and DL 4, two of five pts. In conclusion, in this phase I/II study, we defined the MTD and the dose recommended for the therapy with oral etoposide given over 10 days followed by s.c. GM-CSF in platinum-pretreated patients with advanced ovarian cancer. Our data demonstrate encouraging activity of this regimen and strongly support its further investigation in a phase II study