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Biomedical subjects

R Dubbelman

Publications and source records attributed to R Dubbelman.

30 records · Page 2Linked to original sources
PubMed1990

Dose-finding studies with carboplatin, ifosfamide, etoposide, and mesna in non-small cell lung cancer.

Carboplatin, a clinically active analogue of cisplatin, was added to a regimen containing ifosfamide and etoposide, two agents with proven activity in non-small cell lung cancer (NSCLC). From August 1986 until November 1988, 43 consecutive patients (29 men and 14 women), mean age 57 years, performance status of 2 or less, with symptomatic, inoperable NSCLC were accrued and received carboplatin 100 mg/m2 on days 1, 3, and 5, or 300 or 350 mg/m2 on day 1; ifosfamide 1,500 mg/m2 and etoposide 60 or 100 mg/m2 every 4 weeks. Thirty-four patients were previously untreated, nine had been irradiated before, and two had also received previous chemotherapy. So far, 154 courses have been administered; 19 patients have received four or more courses. With the combination of 350 mg/m2 carboplatin and 100 mg/m2 etoposide, myelosuppression was dose-limiting; nephrotoxicity and neurotoxicity did not occur. Evaluation of response after two or four courses in 40 patients showed an objective response in 40%, whereas 30% progressed during therapy. Carboplatin added to etoposide and ifosfamide is a feasible combination that warrants further study in a randomized fashion.

Adult↗
PubMed1990

Long-term venous access with a Hickman catheter: complications and patient satisfaction.

Hickman catheters can be used to secure prolonged access to the venous system. We have retrospectively analysed the incidence of complications, risk factors for the occurrence of complications and patient satisfaction in 120 catheters. The total number of complications was 30, leading to the removal of 15 catheters. The majority of complications were infectious, occurring 28 times and leading to catheter removal in 13 patients. Other complications (i.e. catheter thrombosis) were rare. The only identifiable risk factor for the occurrence of complications was the male gender, associated with a higher rate of catheter infection. Patient satisfaction after catheter insertion, assessed by a questionnaire to which 24 of the 30 patients responded, was high. This report indicates that the use of Hickman catheters is associated with an acceptable complication rate and a high level of patient satisfaction.

Adolescent↗
PubMed1988

Monitoring of interaction products of cis-diamminedichloroplatinum(II) and cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II) with DNA in cells from platinum-treated cancer patients.

The formation and stability of interaction products between the anti-cancer drug cis-diamminedichloroplatinum(II) (cis-DDP) and DNA were studied in buccal epithelial and urinary cells from ten cancer patients who received cis-DDP-based therapy. Buccal cells were collected 1 h before and 1-2 h after i.v. infusions with cis-DDP. The interaction products were visualized in an immunocytochemical peroxidase assay, using an antiserum against cis-DDP-modified calf thymus DNA. The nuclear staining density was measured by microdensitometry. Nuclear staining densities in buccal cells after infusions of greater than or equal to 20 mg/m2 cis-DDP were always higher than pretreatment values. Repeated sampling from individual patients treated for 2-5 consecutive days with daily doses of 20-70 mg/m2 cis-DDP indicated that cis-DDP-DNA binding in buccal cells increased in proportion to the cumulative total dose of cis-DDP. The variation in dose-density response between patients was 17%. Apparent adduct loss in buccal cells from four patients, as measured 8-17 days after the last infusion, amounted to 67-86%. Platinum-induced DNA modifications could also be detected in buccal cells from two cis-diammine(1,1-cyclobutanedicarboxylato)platinum(II)-treated patients. In vitro experiments with human buccal cells and lymphocytes indicated linear relationships between DNA modification and either cis-DDP concentration or incubation time. Nuclear staining densities in pretreatment buccal cells from ten cancer patients treated in vitro with 33 microM cis-DDP for 1 h revealed that interpatient variation in in vitro DNA modification by cis-DDP was low. No quantitative correlation was found between in situ and in vitro DNA modification.

Carboplatin↗
PubMed1988

Pharmacokinetics of carboplatin after intraperitoneal administration.

The pharmacokinetics of carboplatin, ultrafilterable platinum, and total platinum after intraperitoneal (i.p.) administration were studied in peritoneal fluid, plasma, red blood cells (RBCs), and urine during a phase-I trial in patients with minimal, residual ovarian cancer. Samples were collected from 7 patients who had received carboplatin (200-500 mg/m2) in 21 dialysis fluid. The fluid was withdrawn after a 4-h dwell. Platinum concentrations were measured by flameless atomic absorption spectrometry, and intact carboplatin was determined by HPLC with electrochemical detection. Peak concentrations of carboplatin in plasma were obtained 2 h after the end of instillation. The mean ratio of peak concentrations of carboplatin in instilled fluid and plasma was 24 +/- 11. The peritoneal clearance of carboplatin was 8 +/- 3 ml/min, which was 12 times less than the plasma clearance (93 +/- 32 ml/min). Due to this clearance ratio, the AUCs for the peritoneal cavity were about 10 times higher than those for plasma. On average, 34% +/- 14% of the dose was still present in the instillation fluid that had been withdrawn after a dwell time of 4 h. In plasma, the mean value of AUC/Dnet (Dnet = Dose - amount recovered from the peritoneal cavity) after i.p. administration was comparable with that of AUC/D after i.v. administration. This means that unrecovered carboplatin (66%) was completely absorbed from the peritoneal cavity. It may be expected from this bioavailability that the maximum tolerated dose (MTD) of i.p.-administered carboplatin with a 4-h dwell is around 1.5 times higher than that after i.v. administration. Overall pharmacokinetic parameters of carboplatin and platinum in plasma were comparable after i.p. and i.v. administration.

Aged↗
PubMed1988

Complications of Tenckhoff catheter implantation in patients with multiple previous intraabdominal procedures for ovarian carcinoma.

In patients with minimal residual ovarian carcinoma after aggressive surgical and chemotherapeutic treatment, nephrotoxicity and/or peripheral neuropathy often prohibit continued treatment with intravenous combination cisplatin-based chemotherapy. It is attractive to continue treatment of these patients with intraperitoneal (ip) delivered chemotherapy. From 1981 through 1984 a Tenckhoff catheter was implanted in 59 women for ip chemotherapy after a staging laparoscopy or laparotomy. Minor complications occurred in 8 patients and could be treated conservatively. Ten patients suffered major complications, leading to three (re)laparotomies and catheter extraction in 7 of 10 patients. No patient died of complications, but mean hospitalization time of patients with major complications was 25 days as compared to 11 days for patients without complications. An analysis of nine factors that could lead to postoperative complications failed to reveal a statistically significant risk factor. From this study no profile of a typical high-risk patient emerges.

Adolescent↗
PubMed1985

Phase I study and pharmacokinetics of intraperitoneal carboplatin.

In the early stages of this phase I study the tolerance of carboplatin intraperitoneally was good. Pharmacokinetic profiles suggest a possible therapeutic advantage for giving the drug intraperitoneally for the treatment of tumour nodules situated in the peritoneum. The extent of penetration of carboplatin through tumour nodules has not yet been assessed but tumour nodules are being processed for nuclear activation analysis.

Antineoplastic Agents↗
PubMed1985

Experimental and clinical results with intraperitoneal cisplatin.

Up to 30% of ovarian cancer patients with minimal residual disease may achieve a complete remission with intraperitoneal cisplatin therapy. This mode of therapy, however, is toxic and cumbersome. Sodium thiosulfate was shown to protect renal function, as well as lessen hematologic complications of cisplatin therapy. A major problem with cisplatin in terms of achieving maximal therapeutic dosages is neurotoxicity. Different platinum chemotherapeutic agents, pharmacodynamics, and pharmacokinetics of intraperitoneal administration, and rescue agents other than sodium thiosulfate are presently being investigated by The Netherlands Cancer Institute.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1984

[Main point].

Explore the source record for details and available documents.

Adolescent↗
PubMed1984

Phase I trial of N-methylformamide.

N-methylformamide was administered iv and later orally to 19 patients in a phase I study, with a starting dose of 300 mg/m2/day X 5. The cycles were planned to be repeated every 2 weeks, and doses were escalated in four steps to 1200 mg/m2/day X 5. The principal toxic effect of the drug was nausea and vomiting, but this was not severe enough to interfere with oral medication. Parallel bioavailability studies confirmed excellent absorption of the drug. Biochemical disturbances included reversible elevation in transaminases not related to dose, peripheral neuropathy in one patient, and drug interaction with alcohol in another. The dose-limiting toxic effect was reversible hyperbilirubinemia. One patient became jaundiced. Among 15 evaluable patients, there were two partial responses (prostate and cervix carcinoma) and two minimal responses (ovarian carcinoma and hypernephroma). The recommended dose for the phase II study is 800 mg/m2/day X 5 orally, repeated every 2 or 3 weeks.

Adult↗
PubMedDate not supplied

Hydroxyethylation of hemoglobin by 1-(2-chloroethyl)-1-nitrosoureas.

Following treatment of cancer patients with three 1-(2-chloroethyl)-1-nitrosoureas, hemoglobin was isolated and analyzed by GC-MS for N-(2-hydroxyethyl)-N-terminal valine. This alkylated amino acid was liberated as a (pentafluorophenyl)thiohydantoin from the hemoglobin by a modified Edman degradation procedure. Following intravenous infusion of fotemustine [diethyl[1-[3-(2-chloroethyl)-3-nitrosoureido]ethylphosphonate] (ca. 90 mg/m2) the levels of (hydroxyethyl)valine in two patients increased steadily, reaching a peak of ca. 300 pmol/g after 6 h. In a further five patients receiving fotemustine (100 mg/m2) alkylation levels 24 h after treatment ranged from 132 to 1524 pmol/g of globin. Treatment with TCNU [1-(2-chloroethyl)-3-[2-[(dimethylamino)sulfonyl]ethyl]-1- nitrosourea] or ACNU [1-[(4-amino-2-methylpyrimidin-5-yl)methyl]-3-(2-chloroethyl)-3- nitrosourea] resulted in similar increases in (hydroxyethyl)valine in hemoglobin, although the amounts (as with fotemustine) showed considerable interindividual variation. It appears that the measurement of (hydroxyethyl)valine in hemoglobin may be a suitable monitor of exposure to hydroxyethylating agents during (chloroethyl)nitrosourea chemotherapy.

Alkylation↗