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T A Splinter

Publications and source records attributed to T A Splinter.

At least 37 records · Page 2Linked to original sources
PubMed1992

What is the optimal dose and duration of treatment with etoposide? II. Comparative pharmacokinetic study of three schedules: 1 x 100 mg, 2 x 50 mg, and 4 x 25 mg of oral etoposide daily for 21 days.

The large interpatient and intrapatient pharmacokinetic variability of oral etoposide is well known. We investigated whether dose fractionation would result in less variability. Fifteen patients (five in each etoposide schedule) were given either 100 mg once daily, 50 mg twice daily, or 25 mg four times daily for 21 days. On days 1, 8, and 15 blood samples were collected during 24 hours to measure plasma etoposide levels. Hematologic toxicity was determined by weekly leukocyte and platelet counts and expressed as the relative decrease in these parameters. Once-daily administration of etoposide 100 mg correlated with a significantly higher peak concentration than was observed with the other two schedules. The mean area under the concentration versus time curve (AUC) and mean time with a plasma etoposide concentration above 1 microgram/mL were similar with the three schedules. Peak plasma concentrations, AUCs, and times with plasma concentration above 1 micrograms/mL correlated significantly with the relative decrease in leukocyte but not platelet counts. Large interpatient and intrapatient variability of pharmacokinetic parameters was observed with all three schedules. These data do not support fractionating a daily 100-mg etoposide dose. Moreover, it does not appear useful to adjust oral etoposide doses based on pharmacokinetic data obtained once during a prolonged treatment period. Finally, adjusting oral etoposide doses based on hematologic toxicity seems advisable to decrease the interpatient variability of etoposide's pharmacokinetics.

Administration, Oral↗
PubMed1991

Phase II study of ACNU in non-small-cell lung cancer: EORTC study 08872.

A total of 62 patients with metastatic or locally advanced non-small-cell lung cancer were entered in a phase II study of ACNU. Initially, the drug was given i.v. at a dose of 100 mg/m2 every 6 weeks, but due to observed haematological side effects in chemotherapy-pretreated patients, the dose was lowered in this group to 75 mg/m2. We observed one complete response in a subject exhibiting multiple lung metastases and a partial response in two patients, one showing brain metastases and one who experienced local disease recurrence. The toxicity of ACNU mainly consisted of bone marrow suppression especially thrombocytopenia, with one toxic death occurring due to intracerebral haemorrhage. We concluded that at this dose and on this schedule, ACNU has limited activity in non-small-cell lung cancer.

Adult↗
PubMed1991

Evaluation of CA19-9 serum levels for monitoring disease activity during chemotherapy of pancreatic adenocarcinoma.

Between 1987 and 1990 21 patients with proven adenocarcinoma of the pancreas were treated with chemotherapy in four different phase II studies. For 14 patients, serial measurements of CA19-9 serum levels and clinical evaluations of response by computed tomography scan and/or ultrasound were available. Clinical stable disease and progressive disease were accompanied by stable or exponentially rising serum levels of CA19-9. One patient with clinical partial remission showed a 90% decline of CA19-9. However, a 75% decline of CA19-9 was also observed in a patient with rapidly progressive disease. These data seem to indicate that the CA19-9 serum level may be used as an easy and sensitive tool to evaluate progressive disease during chemotherapy.

Adenocarcinoma↗
PubMed1991

Ifosfamide in advanced adenocarcinoma of the oesophagus or oesophageal-gastric junction area. Rotterdam Esophageal Tumor Study Group.

25 previously untreated patients with inoperable or metastatic adenocarcinoma of the oesophagus or oesophageal-gastric junction area were treated with ifosfamide 6 g/m2 over 48 hours, combined with mesna 6 g/m2. 1 complete response and 1 partial response were seen among 23 patients evaluable, with a response duration of 29+ months and 7 months, respectively. Toxicity was not severe: grade 3 infection in 2 patients, grade 3 leucopenia in 3 patients and grade 3 nausea in 4 patients. No life-threatening episodes or central nervous system toxicity were encountered. Ifosfamide has limited activity in adenocarcinoma of the oesophageal-gastric junction area.

Adenocarcinoma↗
PubMed1991

Elevated serum tumor markers in patients with testicular cancer after induction chemotherapy due to a reservoir of markers in cystic differentiated mature teratoma.

Elevated serum tumor markers in patients with testicular cancer after induction chemotherapy indicate in most instances the presence of residual malignant disease. We describe 2 patients with elevated tumor markers after chemotherapy and before retroperitoneal lymph node dissection who did not prove to have residual malignant disease but cystic differentiated mature teratoma with a high content of alpha-fetoprotein and beta-human chorionic gonadotropin, respectively, in the cysts. It is postulated that leakage of the contents of these cysts to the plasma compartment was responsible for maintaining elevated serum tumor marker levels. Recognition of such entities is of consequence since unnecessary salvage chemotherapy in these patients may be avoided.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Prognostic value of serum thymidine kinase, tissue polypeptide antigen and neuron specific enolase in patients with small cell lung cancer.

In a group of seventy patients with small cell lung cancer the prognostic value of serum tumour markers was determined. Thymidine kinase (TK), tissue polypeptide antigen (TPA) and lactate dehydrogenase (LDH) but not neuron specific enolase (NSE) correlated significantly with survival. Since all markers were strongly interrelated with each other and with the extent of disease, the combined determination of TK, TPA and LDH or the combination of disease extent and a marker yielded no more prognostic information than a single measurement of one of these variables.

Adult↗
PubMed1991

Management of non-small cell and small cell lung cancer.

This review addresses means for the improvement of treatment results in small cell and non-small cell lung cancer. In small cell lung cancer prognostic factors such as the distinction between classic and variant type in vivo remain an important subject for further investigations. Data concerning the schedule dependency of etoposide will lead to the investigation of new treatment regimens. The effect of warfarin is intriguing and warrants further research. Investigations of the damaging effects of prophylactic brain irradiation versus the effect on survival should be awaited before the role of prophylactic brain irradiation can be defined. The role of radiotherapy in the improvement of survival of limited-disease patients remains controversial. In non-small cell lung cancer the role of both radiotherapy and chemotherapy is still a matter of a seemingly never-ending debate. A major problem is the selection of patients. Therefore only randomized phase III trials should be performed in carefully defined subgroups of patients, based upon stage, performance status, and presence or absence of symptoms.

Carcinoma, Non-Small-Cell Lung↗
PubMed1991

Growing teratoma syndrome successfully treated with lymphoblastoid interferon.

In most instances mature teratoma can be successfully resected following chemotherapy for advanced testicular cancer. However, some patients may eventually die because of uncontrollable local growth of an unresectable growing mature teratoma. This is a report on a patient with an unresectable growing mature teratoma in whom a long-lasting disease stabilization was achieved after treatment with lymphoblastoid interferon.

Adult↗
PubMed1991

Radioiodinated somatostatin analog scintigraphy in small-cell lung cancer.

Somatostatin receptors have been characterized on biopsy specimens from small-cell lung carcinoma (SCLC) and on cultured human SCLC cells. We recently described the in vivo visualization of various somatostatin receptor-positive tumors, such as carcinoids and endocrine pancreatic tumors, after injection of 123I-Tyr-3-octreotide, a radiolabeled somatostatin analog. In the present study, this imaging procedure using 123I-Tyr-3-octreotide is reported in 11 patients with lung tumors. In five of eight patients with SCLC (63%), we were able to demonstrate tumor deposits using 123I-Tyr-3-octreotide scintigraphy. Unexpected metastases were found in two patients. In one of three patients with SCLC in whom tumor was not visualized, nonvisualization may have been caused by tumor necrosis and recent radiotherapy. In one of two patients with malignant small-cell tumors as described by Askin, the neoplasm was visualized. Like SCLC, these tumors are thought to derive from neuroendocrine cells. In one patient, a squamous-cell carcinoma and a bronchial adenoma were not visualized. We conclude that in the majority of patients with SCLC, the tumor and its metastases can be visualized using 123I-Tyr-3-octreotide scintigraphy. However, the value of this new technique in terms of specificity and sensitivity requires further studies in a larger group of patients.

Adolescent↗
PubMed1991

Local treatment of liver metastases with recombinant tumour necrosis factor (rTNF): a phase one study.

Fifteen patients with therapy-resistant liver metastases were treated in a phase-I study with recombinant human TNF (rTNF). The rTNF was injected into one liver metastasis by ultrasound guidance, using a 50 microgram escalating dose schedule (3 patients/dosage) ranging from 100-350 micrograms/injection. Influenza-like symptoms like fever, chills, nausea and vomiting were the main clinical side effects. Two patients, treated concomitantly with rTNF and morphine, showed mild hypotension. Other toxicities, as reported after systemic use of rTNF, such as decrease in leukocyte and platelet counts, renal or liver toxicity were not observed. In eight patients growth arrest was observed in rTNF-treated metastases, whereas non-injected lesions showed growth progression. The maximum tolerated dose by this route of administration is greater than 350 micrograms/injection. Based on these observations it is concluded that the toxicity of rTNF injected into liver metastases by sonographic control is transient and mild and that intratumoural administration of rTNF might play a role in local tumour control.

Adult↗
PubMed1990

Chemotherapy as treatment of choice in extrapulmonary undifferentiated small cell carcinomas.

Extrapulmonary undifferentiated small cell carcinomas, especially those arising in the upper aerodigestive tract, form a group of neoplasms with a clinical behavior which resembles small cell carcinoma of the lung. In 11 patients treated by combination chemotherapy an objective response rate of 82% was achieved for a median duration of 8+ months. Median survival for all patients was 12 months. Long-term survival was observed in those patients with limited disease who achieved a complete response after chemotherapy followed by radiotherapy.

Adult↗
PubMed1990

Chemotherapy in advanced non-small cell lung cancer.

Chemotherapy in advanced non-small cell lung cancer (NSCLC) has been evaluated with response rate, survival and quality of life as criteria. The data were collected from 142 phase II and III trials. The three main conclusions are: (1) multivariate landmark analyses show that a response to chemotherapy has an independent significant value for prognosis, and all studies of chemotherapy vs. best supportive care show some survival benefit in favour of chemotherapy; (2) NSCLC patients are a heterogeneous group with a large variation of known and unknown prognostic factors, such as the treatment centre, for both response and survival; and (3) retrospective analysis of the data show that response rate and survival are significantly correlated at response rate over 30% and in limited disease patients. The following recommendations are made: (1) new drugs should be compared in randomised phase II trials with a standard active drug; (2) randomised phase III trials of single agents or best supportive care vs. combination chemotherapy should be repeated in a well-defined subgroup of patients with a high performance score and limited tumour load; and (3) the palliative effect of chemotherapy in randomised trials in patients with symptoms should be investigated with relief of symptoms and quality of life as endpoints.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

Diagnostic value of anti-neuronal antibodies for paraneoplastic disorders of the nervous system.

The diagnostic value of the presence of anti-neuronal antibodies in serum was examined in 21 patients suspected of paraneoplastic disorders of the nervous system (NS) (group 1) and was compared to three control groups; group 2: 25 patients with a neurological disease, without cancer and no sign of paraneoplastic disorder; group 3: 27 patients with neurological disease and cancer and no signs of a paraneoplastic disorder; group 4: 94 patients with cancer and without neurological disease. In group 1, anti-neuronal nuclear antibodies were detected in eight patients (38%), in titres from 1:1000 to 1:32,000. A small cell lung cancer was present in six patients, ovarian cancer in one patient and in one patient no tumour could be detected. The neurological symptoms preceded a diagnosis of cancer in five out of eight patients. Anti-neuronal antibodies were found in the serum of two out of 94 patients (2%) from control group 3 but not in serum from any of the other control groups. These data indicate a moderate sensitivity of 38%, but a high specificity of 98.6% (95% confidence interval 95.5-99.8%) for the presence of anti-neuronal nuclear antibodies if a paraneoplastic NS disorder is suspected.

Autoantibodies↗
PubMed1990

Choriocarcinoma with lung metastases during pregnancy with successful delivery and outcome after chemotherapy.

A patient with an intrauterine pregnancy of 27 weeks had a coexisting pulmonary metastatic choriocarcinoma. On the chest radiograph the lung metastases appeared as pulmonary infiltrates, simulating atypical pneumonia. Serum human chorionic gonadotrophin levels were normal for gestational age. Treatment with methotrexate was successful. This is the first reported case of choriocarcinoma in a woman with a pregnancy of less than 35 weeks in which both mother and child survived. The case emphasises the need to consider choriocarcinoma in any pregnant woman who presents with haemoptysis and pulmonary nodules or infiltrates.

Adult↗