Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy.

PURPOSE: To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy. MATERIALS AND METHODS: 82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m(2)/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1-5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2-6. RESULTS: Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1-5, days 6-9 and days 1-9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1-9 (P = 0.029). During the entire period (days 1-9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P = 0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P = 0.037). Side effects were generally few and mild with both treatments and no significant differences were seen. CONCLUSION: Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin(1) receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.

Effect of topotecan on serum CA-125 in patients with advanced epithelial ovarian cancer.

The effect of topotecan on CA-125 serum levels was evaluated in 30 patients with advanced epithelial ovarian cancer. All patients had progressive disease and were relapsing during (11 patients) or after (19 patients) chemotherapy containing paclitaxel and platinum. Topotecan (1.0 mg/m(2)/day) was administered intravenously on Days 1-5 every 3 weeks. The patients had received a median of 2 (1-5) prior regimens. Four patients had increased CA-125 only, and 26 had both measurable disease and increased CA-125. Two patients (7%) achieved a clinical partial response with durations of 5 and 10+ months, respectively. Eighteen other patients (60%) exhibited no clinical change with a median duration of 5+ months (range: 2-11+ months). Among these patients 9 (30%) had a biochemical response. The rate of change in CA-125 (s, slope of the exponential regression curve) during treatment with topotecan was compared with s over a period before treatment. A decrease in s was observed in 20 patients (74%). Comparing the mean values of s before and during topotecan, a significant (P = 0.005) decrease was seen in the CA-125 serum levels. The mean doubling times before and during treatment were 59 and 1421 days, respectively. Toxicity was mainly hematologic. Neutropenia grades III and IV were seen in 16 and 10 patients, respectively. No patients died due to side effects. Generally the side effects were mild to moderate. In conclusion, at the given dose intensity topotecan shows activity in advanced paclitaxel- and platinum-resistant ovarian cancer based on CA-125 measurements.

Electron microscopy of treponemes subjected to the Treponema pallidum immobilization (TPI) test. II. Immunoelectron microscopy.

The experiments were carried out in order to investigate whether human IgG globulin is absorbed on to the surface of T. pallidum cells during incubation with human syphilis serum in the Treponema pallidum immobilization (TPI) test. Cells of T. pallidum Nichols subjected to the TPI test were further incubated with ferritin conjugated rabbit antihuman IgG globulin. Human IgG globulin could only be demonstrated on immunoimmobilized cells, i.e. cells incubated with human syphilis serum and unheated guinea pig serum (GPS). The surface of the swollen cells was completely covered by a fuzzy layer on to which the ferritin molecules appeared to be attached. In ultrathin sections of cells obtained from the same suspensions the surface of the outer cell membrane was outlined by ferritin molecules. In these cells a rather wide gap was observed between the outer membrane and the cytoplasmic membrane. The ribosomes seemed to have disappeared from the cytoplasm of the immunoimmobilized treponemes, but were present in motile cells obtained from control incubations.

Electron microscopy of treponemes subjected to the Treponema pallidum immobilization (TPI) test. I. Comparison of immunoimmobilized cells and control cells.

The ultrastructure of cells of T. pallidum Nichols subjected to the TPI test was studied in negatively stained specimens. Cells incubated in basal medium to which was added either human syphilis serum or heated guineapig serum (GPS) showed a normal morphology. This was also the cause for cells incubated with basal medium to which was added either human syphilis serum and heated GPS or normal human serum and unheated GPS. By dark-field microscopy cells obtained from these different incubation mixtures were found to be motile. In contrast, cells incubated in basal medium to which was added human syphilis serum and unheated GPS were all immobilized, and in the electron microscope they presented a morphology strikingly different from that of normal cells. The immunoimmobilized cells were swollen and their surface was completely covered with a layer of fuzzy material. The nature of this material and its possible role in rendering the treponemes immobile is discussed.