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S Rodenhuis

Publications and source records attributed to S Rodenhuis.

153 records · Page 9Linked to original sources
PubMed1985

Inefficacy of plasma exchange in cold agglutinin hemolytic anemia--a case study.

A therapeutic trial of plasma exchange was conducted in an 82-year-old woman with severe cold agglutinin hemolytic anemia, who was unresponsive to conventional treatment. In spite of considerable improvement of pertinent parameters (total IgM, cold agglutinin titer and thermal amplitude) this treatment failed to induce a clinical remission. This failure may be the result of the ability of the cold agglutinin to fix complement to the red cell membrane at temperatures much higher than the thermal amplitude. A simple laboratory test to detect this dissociation between complement fixing ability and agglutination activity is described.

Aged↗
PubMed1984

Phase I evaluation of SOAz (1,3,3,5,5 pentakis(aziridino)-1 lambda 6, 2,4,6,3 lambda 5, 5 lambda 5 thiatriaza-diphosphorine-1-oxide) in a weekly schedule.

Eleven patients with advanced cancer were treated with SOAz, the first aziridino substituted inorganic heterocyclic compound to undergo phase I clinical trials. The agent was administered as a rapid i.v. infusion once a week in a dose of 50, 75 or 100 mg/m2. Severe myelotoxicity, which was prolonged and delayed in onset, precluded continuing treatment for more than three courses in 9 of 11 patients. In two patients thrombocytopenia showed no signs of recovery 9 and 11 weeks after the last infusion. Two minor responses were noted and there was one therapy-related death. Because of severe myelotoxicity, which is cumulative and may be irreversible, this treatment schedule seems unsuitable for phase II studies.

Adult↗
PubMed1984

Patient motivation and informed consent in a phase I study of an anticancer agent.

In order to evaluate the quality of an informed consent procedure (I.C.P.) 48 patients with advanced cancer were offered participation in a phase I clinical trial and entered an I.C.P. consisting of three separate conversations. In the first session, the possible risks and benefits of a phase I study were informally explained by the patient's personal physician. The second session was attended by the patient, a relative, a registered nurse and a physician; the third session was held at least 5 days after the second. Forty-one patients gave their consent motivated by hope for improvement of their conditions, pressure exerted by relatives and friends, the desire to contribute to the progress of medicine or simply because they felt they had 'no choice'. Encouragement by relatives or friends seems to be a powerful incentive to participate. A period of a few days to consult relatives, friends or trusted physicians as a part of the procedure seems helpful in arriving at a well-considered decision.

Adult↗
PubMed1983

Determination of the antitumor agent SOAz (1,3,3,5,5 pentakis(aziridino)-1 lambda 6,2,4,6,3 lambda 5, 5 lambda 5 thia-triazadiphosphorine-1-oxide) by a gas chromatographic assay suitable for pharmacokinetic studies in man.

A sensitive method, based on capillary gas chromatography using a thermionic detector, has been developed for the new antitumor agent pentakis(aziridino)-thiatriazadiphosphorine-oxide, (NPAz2)2NSOAz ('SOAz'), in order to obtain pharmacokinetic data from patients receiving this drug IV in clinical trials. A structural analog of SOAz, (NPAz2)2NSOPh ('SOPh'), was used as an internal standard. The detection limit of SOAz with this method was 0.01 mg/l for serum and 0.04 mg/l for urine. The coefficient of variation (n = 10) was 6,0% at 1.5 mg/l in serum and 1.6% at 75.0 mg/l in urine. Analytical recoveries averaged 89.9% from serum and 86.7% from urine. In two patients treated with subtoxic doses of SOAz (55 mg/m2), serum levels were found ranging from 3.0 to 0.16 mg/l at 10 min and 12 h, respectively, after administration. This assay seems to be useful for determining SOAz in samples from patients receiving subtoxic doses of SOAz.

Aged↗
PubMed1983

Clinical pharmacokinetics of (NPAz2)2NSOAz: 'SOAz'.

Pharmacokinetic studies of 1,3,3,5,5 pentakis (aziridino)-1 lambda 6,2,4,6,3 lambda 5,5 lambda 5 thiatriazadiphosphorine-1-oxide ('SOAz'), a new antineoplastic agent containing an inorganic ring system and five aziridino groups, were performed in six patients who took part in a phase I clinical trial of the agent. The drug was administered as a rapid IV infusion. Serum decay curves could be fitted to an open two-compartment model of drug disappearance. After a short initial phase with a t 1/2 (+/- SD) of 7.8 +/- 4.2 min a terminal phase with a dose-independent half-life of 203 +/- 17 min occurred. The coefficient of apparent distribution was 0.71 +/- 0.13. The renal clearance was 75 +/- 11 ml/min and the total body clearance 162 +/- 23 ml/min. A percentage of 46.5 +/- 6.6 of the administered drug could be recovered unchanged in the urine within 24 h. It is concluded that in view of concentrations known to be effective in vitro, administration in large single doses may be advantageous. Dose adjustments should be made for patients with impaired renal function.

Adult↗
PubMed1983

Phase I clinical trial of (NPAz2)2NSOAz: 'SOAz'.

(NPAz2)2NSOAz ('SOAz') is the first of a new class of cytotoxic agents containing an inorganic heterocyclic ring system to enter clinical trial. It was used to treat 31 patients with advanced cancer by IV infusion over 30 min on days 1, 2, 3, and 4 of a 21-day cycle, which was postponed if necessary to allow for hematological recovery. A total of 46 courses evaluable for toxicity was given and the tumor response was evaluable in 21 patients. Seven dose levels, ranging from 25 mg/m2 to 300 mg/m2, were studied, with three to six patients at each level. The only major toxicity was myelosuppression, especially thrombocytopenia, which was dose-limiting. Platelets decreased from the 14th day onward, with a nadir 4-5 weeks after administration. Leukopenia was less predictable and reached a nadir 3-5 weeks after administration. In most patients recovery was complete after 6-9 weeks. Myelosuppression was clearly cumulative in succeeding courses and proved irreversible in three patients. Anemia also occurred, but otherwise SOAz was remarkably well tolerated. There were no responses and no therapy-related deaths. The highest tolerated dose for patients who had received no or only minor chemotherapy prior to treatment with SOAz was 300 mg/m2, and that for heavily pretreated patients, 175 mg/m2. Because of cumulative myelotoxicity phase II studies with SOAz are not recommended.

Adult↗
PubMedDate not supplied

Palliative chemotherapy after failure of high-dose chemotherapy in breast cancer--toxicity and efficacy.

We evaluated the toxicity and efficacy of the first palliative chemotherapy regimen after failure of high-dose chemotherapy in 148 patients with primary or metastatic breast cancer treated with high-dose chemotherapy (one full dose CTC, (cyclophosphamide 6000 mg/m2, thiotepa 480 mg/m2, carboplatin 1600 mg/m2) or multiple courses CTC or 'tiny' CTC (tCTC) (two-thirds of the agents of the full-dose regimen), all divided over 4 days). After a median follow-up time of 46.8 (range 1-120) months, 79 patients had a relapse or progressive disease and 41 patients were treated with palliative chemotherapy. The most commonly used regimens were classical CMF (n = 13), docetaxel (n = 16) and less frequently anthracycline (n = 4), paclitaxel (n = 5), capecitabine (n = 2) and vinorelbine (n = 2). In both the CMF and docetaxel group, 3 patients required a dose reduction because of hematological toxicity. Objective responses were seen with CMF (23%) and docetaxel (69%) with a median duration of 161 (range 28-481) and 196 (range 62-437) days, respectively. We found no relationship of toxicity and response with treatment-free interval after high-dose chemotherapy. This report shows that conventional-dose palliative chemotherapy regimens may be safe and effective after failure of high-dose chemotherapy.

Antineoplastic Agents, Phytogenic↗
PubMedDate not supplied

Mobilisation of blood progenitor cells with ifosfamide and etoposide (VP-16) in combination with recombinant human G-CSF (Filgrastim) in patients with malignant lymphomas or solid tumours.

The mobilisation characteristics of ifosfamide and etoposide followed by Granulocyte Colony-Stimulating Factor fGCSF, filgrastim) were analysed in 17 patients with malignant lymphoma and 24 patients with solid tumours, with respect to the optimum time to harvest progenitor cells and to the yields of progenitor cells that could be achieved. In addition, we analysed patient characteristics which could influence the size of the progenitor cell harvest. Clinical parameters which were co-related with the size of the circulating progenitor cells (CPC) harvests were: the dose of G-CSF, dose of if osfamide, sex, age, diagnosis and extent of pretreatment. CPC were mobilised with 3 g/m2 (n = 11) or 4 g/m2 (n = 30) ifosfamide on day 1 and etoposide 100 mg/m2/day, on days 1-3 i.v., followed by daily s.c. injections with filgrastim 5 micrograms/kg (n = 26) or 10 micrograms/kg (n = 15) from day 4. The maximal progenitor cell harvest was achieved on either day 12 or day 13 after the start of the ifosfamide/etoposide course. The median number of leukaphereses necessary to harvest the target quantity of 3 x 10(6) CD34+ cells/kg body weight was 1 (range 1-9). Thirteen/41 (32%) of the patients did not achieve the target yield of 3 x 10(6) CD34+ cells/kg. By multivariate analysis, the dose of GCSF and prior irradiation were associated with the number of progenitor cells harvested, while all other parameters, induding the dose of if osfamide and number of previous chemotherapy courses, were not. Sixteen patients received two or more mobilisation courses. Despite the fact that the same mobilisation schedule was used, the progenitor cell yields after the first mobilisation course did not predict the results after the subsequent mobilisation courses, indicating that unknown transient factors may significantly influence the CPC yield.

Adolescent↗