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T A Splinter

Publications and source records attributed to T A Splinter.

At least 73 records · Page 4Linked to original sources
PubMed1992

The European Organization for Research and Treatment of Cancer experience with teniposide: preliminary results of a randomized study in non-small cell lung cancer.

Chemotherapy for non-small cell lung cancer (NSCLC) is unsatisfactory, and the search for new active drugs has been relatively unsuccessful. Most polychemotherapy regimens in NSCLC include cisplatin with a vinca alkaloid or etoposide. Among the new agents tested in recent years, teniposide produced a 17% response rate in 42 evaluable patients, with a 21% response rate in untreated patients. The Lung Cancer Cooperative Group of the European Organization for Research and Treatment of Cancer has started a randomized trial comparing two different schedules of teniposide administration with and without cisplatin. This paper reports the preliminary findings for the initial 80 patients in this randomized study.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Absolute bioavailability and pharmacokinetics of oral teniposide.

The absolute bioavailability and pharmacokinetics of orally administered teniposide were investigated in 25 patients. All patients received 50 to 60 mg/m2 teniposide intravenously on day 1, before oral administration. Six patients received 60 mg/m2 as a single oral dose on day 8; 5 patients received 60 mg/m2 and 120 mg/m2 as a single oral dose on days 8 and 15, respectively; 5 patients received 120 mg/m2 and 240 mg/m2 as a single oral dose on days 8 and 15, respectively; 6 patients received 60 mg/m2 as a single oral dose on 5 consecutive days from days 8 to 12; and 3 patients received 50 mg/m2 three times a day at 6-hour intervals on day 8. The mean absolute bioavailability was 41.6% +/- 14.2% with a large interindividual variability (range, 19.7% to 71.4%) and a low intraindividual variability (range, 2.8% to 13.9%). At a dose of 240 mg/m2, the bioavailability was decreased, whereas administration of multiple doses on 1 day or 5 consecutive days increased the overall bioavailability. In conclusion, teniposide can be administered orally with a bioavailability comparable with that of etoposide. The schedule dependency of both drugs warrants investigations of oral administration for 21 or more days. A formulation of teniposide capsules of 50 mg or less would be most helpful to facilitate oral administration.

Absorption↗
PubMed1992

A phase I study of daily oral teniposide for 20 days.

In this phase I study, teniposide was administered orally for 20 consecutive days to patients with refractory cancers. All patients but one were pretreated. When given for 20 consecutive days, the maximum tolerated dose of teniposide was 100 mg/d. Myelosuppression was the dose-limiting toxicity, and occurred between days 17 and 31. In all patients blood counts had sufficiently recovered by day 35 to begin another 20-day course. Gastrointestinal toxicity persisted in 6 of 15 patients despite antiemetics. Total alopecia was observed in 10 of 13 patients at risk. We recommend teniposide 100 mg/d for 20 consecutive days for evaluation of antitumor efficacy in phase II studies.

Administration, Oral↗
PubMed1992

Teniposide (VM-26) in ovarian cancer: a review.

Relatively few patients with gynecologic malignancies have been included in trials with teniposide given as a single agent. For 109 patients with advanced ovarian cancer treated with various doses and schedules, an overall response rate of 12% was reported. Most patients were heavily pretreated and presumably had resistant disease. Information about teniposide's activity in combination with other cytotoxic agents, as well as its efficacy in other gynecologic malignancies, is limited. In view of the favorable pharmacologic and toxicity profiles of teniposide and its possible synergism with cisplatin and carboplatin, new treatment strategies are discussed that may have implications for further investigation of the usefulness of teniposide in advanced ovarian cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

What is the optimal dose and duration of treatment with etoposide? I. Maximum tolerated duration of daily treatment with 50, 75, and 100 mg of oral etoposide.

Because etoposide is a cell-cycle phase-specific drug, its degree of cytotoxicity likely relies on duration of cell exposure to a specific concentration. We investigated the maximum tolerated duration of oral etoposide treatment at doses of 100, 75, and 50 mg/d in previously treated patients with biopsy-proven, advanced cancer. "Maximum tolerated" was defined as tumor progression or hematologic toxicity (World Health Organization [WHO] grade > or = 2). The maximum tolerated duration in 19 patients given 100 mg/d was > or = 21 days, since this was the predetermined cutoff point; 3 patients discontinued etoposide because of early tumor progression, and 6 others had developed leukopenia or thrombocytopenia (WHO grade > 2) by day 21. The maximum tolerated duration in 13 patients given 75 mg/d was a median of 11 weeks (range, 2 to 19); 6 patients developed tumor progression and 6 others leukopenia (WHO grade > or = 2) requiring discontinuation of treatment. Ten patients given 50 mg/d tolerated therapy for a median of 13 weeks (range, 3 to 26 weeks); treatment was halted in seven patients because of tumor progression, two because of leukopenia (WHO grade > or = 2), and one because of stomatitis. The data from this study and others suggest that above a certain minimal plasma level, etoposide induces concentration-dependent cumulative toxicity. What remains to be determined is the minimal plasma level per tumor type. It will also be interesting to see whether myelopoiesis, thrombocytopoiesis, and erythropoiesis have differential sensitivity to etoposide, since thrombocytopenia did not occur using daily etoposide doses of 50 and 75 mg, whereas at the same doses 10 of 23 patients required erythrocyte transfusion.

Administration, Oral↗
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↗