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Biomedical subjects

G Stoter

Publications and source records attributed to G Stoter.

At least 163 records · Page 9Linked to original sources

Stenting in malignant vena caval obstruction.

BACKGROUND: For patients with recurrent vascular obstruction of the vena cava due to tumor regrowth after chemotherapy or radiation therapy and occasionally surgery, no current therapy is available. With the development of intravascular stenting, a new option becomes available in the treatment of a vena caval syndrome. METHODS: Twenty-two patients were treated for malignant obstruction of the vena cava by single, double, and triple Z-type metal stents. All patients had been pretreated extensively and their disease was not amenable to other therapeutic techniques at the time of stenting. RESULTS: Correct positioning of the stents was achieved in all patients. In 68% of patients (n = 15), the symptoms completely disappeared without recurrence until death as a result of tumor progression. In 18% of patients (n = 4), a remarkable improvement was observed, but there was no complete disappearance of symptoms. In 14% of patients (n = 3), reocclusion of the vena cava occurred. The median survival time was 3.0 months (range, 1 week to 9 months). CONCLUSIONS: The application of Z-type metal stents in patients with recurrent malignant obstruction of the vena cava appears to be a useful palliative procedure.

Constriction, Pathologic↗

Phase II study of daily oral miltefosine (hexadecylphosphocholine) in advanced colorectal cancer.

34 patients with metastatic colorectal cancer were treated with the ether lipid miltefosine (hexadecylphosphocholine). Most patients received 3 x 50 mg daily, while in 11 patients the dose could be escalated to 4 x 50 mg daily. Nausea and vomiting were the most frequent side-effects occurring in all but 3 patients, nephrotoxicity was observed in 11 patients. Leucocytosis was observed in 24 and thrombocytosis in 17 patients. 28 patients are evaluable for response. 1 patient obtained a partial response of liver metastases for a duration of 8 months. 3 patients had stable disease while 24 progressed during treatment. We conclude that miltefosine in this dose and schedule has limited activity in colorectal cancer.

Administration, Oral↗

Prognosis after resection of residual masses following chemotherapy for metastatic nonseminomatous testicular cancer: a multivariate analysis.

Following chemotherapy for metastatic nonseminomatous testicular cancer, 86 patients with normal serum markers AFP and HCG underwent resection of residual tumour masses (63 laparotomy, 11 thoracotomy, 12 both). Prognostic factors for relapse and survival were analysed with Kaplan-Meier curves and Cox regression analysis. Putative prognostic factors included age, the primary histology, prechemotherapy level of the tumour markers AFP and HCG, the extent of disease (lymph nodes, lung and hepatic metastases) before and after chemotherapy, the histology of the resected material and the completeness of the surgical procedure. Eleven patients relapsed during follow-up (median 47 months), accounting for a 5 year relapse free percentage of 87.4%. Adverse prognostic factors were (1) prechemotherapy level of HCG (> or = 10,000 IU l-1; (2) incomplete resection; and (3) the extent of disease, especially of lung metastases (prechemotherapy number < or = 3,4-19, > or = 20; or size after chemotherapy > 1 cm; or presence of any residual lung metastasis after chemotherapy without residual abdominal metastases). The histology found at resection was not associated with the risk of relapse, which might be explained by the effectiveness of postresection chemotherapy, which in the majority of these patients was a salvage regimen rather than two further cycles of the initial cytostatics. A good and a poor risk group were formed, based on HCG level and completeness of resection. The effect of salvage chemotherapy after resection of viable cancer cells needs further investigation.

Adult↗

Phase I/II study of a short course of weekly cisplatin in patients with advanced solid tumours.

Twenty-five patients with advanced solid tumours were entered in a phase I/II study of six, weekly cycles of cisplatin. Nineteen patients were chemonaive and six were previously treated. The starting dose was 50 mg m-2 week-1. This dose could be escalated without major toxicity to 70 mg m-2 week-1. At a dose of 80 mg m-2 myelosuppression grade 3 occurred as well as grade 1 nephro- and neurotoxicity. The maximum tolerated dose was 85 mg m-2 with dose limiting thrombocytopenia. Hypertonic saline was effective in preventing nephrotoxicity. Ondansetron was a very effective antiemetic in the first weeks of treatment but its efficacy waned later on. Responses were observed in head and neck cancer, melanoma and mesothelioma. At the dose level of 80 mg m-2 the optimal dose intensity was reached. This schedule will be tested further in phase II studies.

Adult↗

Oral piritrexim, an effective treatment for metastatic urothelial cancer.

Piritrexim is a lipid-soluble inhibitor of dihydrofolate reductase (DHFR) that enters tumour cells rapidly by passive diffusion, cannot be polyglutamated, and is as effective as methotrexate in inhibiting DHFR. Bioavailability after oral dosing is approximately 75%. We performed a phase II study with oral piritrexim in non-chemotherapy pretreated patients with metastatic urothelial cancer. Thirty-three patients were treated with 25 mg three times daily for 5 consecutive days, repeated weekly, with provision for dose escalation or reduction according to the toxicity observed. Of 29 evaluable patients, one patient achieved a complete response of 19+ weeks duration, and ten patients achieved a partial response with a median duration of 22 weeks (range 16-48), for a total response rate of 38%. Piritrexim was generally well tolerated, with myelosuppression as the major toxicity, that frequently required dose modification. We conclude that piritrexim appears to be an active agent in patients with metastatic urothelial cancer when administered as a 5-day, low-dose oral schedule. It would be attractive to investigate the combination of piritrexim and cisplatin.

Administration, Oral↗

Phase II study of oral administration of etoposide for patients with well- and moderately-differentiated adenocarcinomas of unknown primary site.

BACKGROUND: The prognosis of patients with well- and moderately-differentiated adenocarcinomas of unknown primary is poor, as a consequence of chemotherapy resistance. PATIENTS AND METHODS: We performed a phase II study with prolonged oral administration of etoposide in 25 chemotherapy-naive patients with well- and moderately-differentiated adenocarcinomas of unknown primary site. The treatment regimen was 50 mg/m2 for 21 days, every four weeks. RESULTS: Of 24 evaluable patients, two achieved partial responses (8%) lasting 15+ and 17 months, 11 patients had stable disease, and 11 progressed during treatment. The major toxicity was myelosuppression. WHO grades 3 or 4 leukocytopenia was seen in six patients but confined to the first treatment cycle in five of them. Four of these latter five patients already had disease progression after one treatment cycle. A primary tumor site was later identified in four patients, three colon carcinomas and one carcinoma of the pancreas. CONCLUSION: Etoposide given in this dose and schedule has only limited activity in patients with well- or moderately-differentiated adenocarcinomas of unknown primary site.

Adenocarcinoma↗

Piritrexim-induced pulmonary toxicity.

We describe a patient with transitional cell carcinoma of the renal pelvis who developed respiratory dysfunction and an abnormal chest x-ray with diffuse interstitial opacities while on chemotherapy with piritrexim, a methotrexate analog. Drug discontinuation resulted in complete resolution of the clinical and radiographic picture. The pulmonary toxicity is probably induced by piritrexim.

Aged↗

Activation of the immune system of cancer patients by continuous i.v. recombinant IL-2 (rIL-2) therapy is dependent on dose and schedule of rIL-2.

The effect of dose and schedule of continuous i.v. rIL-2 infusions on leucocyte subset counts, activation status of CD56+CD3- natural killer (NK) and CD3+ T lymphocytes, and cytolytic activities of peripheral blood mononuclear cells (PBMC) was studied. A single 4-day course of rIL-2 in escalating doses (0.9-11.5 x 10(6) U/m2 per day) was given to 18 patients with various types of metastatic cancer. The serum IL-2 concentration during rIL-2 therapy ranged between 23 and 64 U/ml and was proportional to the administered rIL-2 dose, as was the rebound lymphocytosis following therapy. Before therapy, the CD56+CD3- NK cells expressed low levels of the p75 chain of the IL-2 receptor (IL-2R) and virtually no IL-2R(p55). Most CD3+ T cells were IL-2R(p55-,p75-). Between 2 and 4 days following therapy, i.e. at the time of lymphocytosis, the percentage of CD56+,CD3- NK cells among the lymphocytes had increased proportional to the administered rIL-2 dose. The levels of IL-2R(p75) expression by the CD56+,CD3- NK cells had increased. The percentages of CD3+ T cells expressing IL-2R(p55), HLA-DR and CD45RO had increased proportional to the administered rIL-2 dose. The level of lymphokine- activated killer (LAK) activity against Daudi cells was also positively correlated with rIL-2 dose. Subsequently, seven patients received 4-weekly cycles of rIL-2 (2.9-4.4 x 10(6) U/m2 per day) during 4 consecutive weeks. This schedule led to marked increments in lymphocyte and eosinophil counts, and to increased cytolytic activities compared with pretreatment. We conclude that CD56+,CD3- NK and CD3+ T cells are activated differentially by continuous i.v. rIL-2 proportional to dose and duration of treatment.

Cytotoxicity, Immunologic↗

Prognostic factors in metastatic non-seminomatous germ cell tumours: an interim analysis of the EORTC GU-Group experience.

Univariate and multivariate analyses were performed in 632 patients treated with cisplatin combination chemotherapy for metastatic non-seminomatous testicular germ cell tumours. Multivariately, the most important poor prognosis factors for the prediction of survival were: HCG > or = 10,000 IU/l, lung metastases > or = 10, abdominal metastases with a horizontal diameter of > or = 5 cm and the presence of supraclavicular metastases. If patients had 2 or more of these factors the death rates increased from 30% for patients with 2 factors to 65% for patients with 3 or 4 factors. The patients studied here are not a random sample of the metastatic testicular cancer patients in general, as the population studied comprised a large proportion of low volume metastatic disease patients. Therefore, the final analysis will include patients from all the recently completed trials.

Analysis of Variance↗

Interleukin-2-induced thyroid dysfunction is correlated with treatment duration but not with tumor response.

PURPOSE: To analyze the putative relationship between immunotherapy-associated dysthyroidism and the probability of a tumor response. PATIENTS AND METHODS: A total of 89 consecutive patients with advanced cancer were treated with interleukin-2 (IL2)-based immunotherapy in a prospective study. RESULTS: Twenty patients developed thyroid dysfunction. Repeatedly positive tests for thyroid antibodies developed in 28% of the patients. Twenty-two patients achieved a response. There was no relationship between the formation of antibodies and the probability of response. There appeared to be a trend toward a relationship between thyroid dysfunction and response (P = .23). A strong relationship was found between response on the one hand and cumulative dose of IL2 (P = .01) and treatment duration with IL2 (P = .025) on the other. The frequency of thyroid dysfunction was also significantly correlated with treatment duration (P = .001). After adjustment for cumulative dose of IL2 and treatment duration, no relationship between thyroid dysfunction and response remained (P = .99). CONCLUSION: There is no relationship between thyroid dysfunction and the probability of tumor response. Thyroid dysfunction is merely a function of treatment duration and cumulative dose of IL2.

Adult↗

Optimization of culture conditions for activation and large-scale expansion of human T lymphocytes for bispecific antibody-directed cellular immunotherapy.

We investigated the optimal culture conditions (i.e., activation procedure, medium composition and type of culture vessel) for rapid in vitro expansion of large numbers (greater than 5 x 10(9) of blood T lymphocytes. These expanded lymphocytes can be targeted to be cytotoxic to ovarian carcinoma cells with a bispecific monoclonal antibody (BsAb) specific for CD3 and for the ovarian carcinoma-associated antigen MOv18. Both phytohemagglutinin (PHA) and monoclonal antibody (MAb) CD3 induced rapid T-cell proliferation, although the growth kinetics after PHA activation were slightly faster. A 50-fold increase in cell number was obtained after 14 and 16 days for PHA and CD3 MAb, respectively. The induction of BsAb-directed cytolysis was faster after CD3 MAb than after PHA activation of lymphocytes, but became similar around day 20. A mixture of media consisting of 78% RPMI 1640, 20% AIM-V and 2% human plasma (Mix-med) yielded better results than 100% AIM-V medium. Culture of lymphocytes in polyolefin bags, compared with tissue culture flasks, or cryopreservation did not affect lymphocyte yield and function. In most cultures the proportion of CD8+ lymphocytes increased, suggesting a growth advantage of CD8+ over CD4+ lymphocytes in this culture system. A protocol employing PHA activation, Mix-med and polyolefin bags has been used successfully to activate and expand blood lymphocytes for the first 5 patients entered into a phase-I/II clinical trial for the intraperitoneal treatment of ovarian carcinoma using CD3 x anti-MOv18 BsAb-directed T lymphocytes.

Antibodies, Monoclonal↗

A dose-finding study of miltefosine (hexadecylphosphocholine) in patients with metastatic solid tumours.

The ether lipid miltefosine (hexadecylphosphocholine) was orally given to patients with various tumours in a dose-finding study. All patients initially received a daily total dose of 100 mg, which in the absence of side-effects was increased to 150 mg and further to 200 mg. A total of 54 patients were entered and were evaluable for gastrointestinal toxicity. Nausea and vomiting were found to be dose-limiting; 22% of patients ultimately tolerated a dose of 100 mg, 59% tolerated a dose of 150 mg and 19% tolerated a dose of 200 mg. In addition 30% of patients developed renal dysfunction, which was thought to be related to the drug. No other toxicities were observed. For further phase II studies it is recommended that one starts with a dose of 150 mg daily, divided over three administrations.

Adult↗

Phase I study of intravenous fosquidone (GR63178A-NSC D611615) using a three times a week schedule.

In a Phase I study fosquidone was administered to 23 patients (15 female, 8 male; mean age 53.6 years) with various solid tumours. Increasing doses (50-325 mg/m2) were given intravenously three times a week for 3 weeks. The MTD was established a 325 mg/m2 dose, the dose limiting factor being phlebitis in two of three patients. The other main side-effects were headache (9 patients), pain (11 patients) and nausea and vomiting (16 patients). The majority of these were mild (WHO grade 1-2), but two patients reported WHO grade 3 and 4 pain. There was no clear relationship between dose, severity and frequency of side-effects. Four tumour regressions (three minor and one partial response) were achieved at varying dose levels (50, 100, 160 and 325 mg/m2) in patients with different tumours (laryngeal, colorectal and lung). The recommended dose for Phase II studies is 250 mg/m2 given intravenously three times a week for 3 week.

Adult↗