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T A Splinter

Publications and source records attributed to T A Splinter.

At least 19 recordsLinked to original sources
PubMed1992

Extra-uterine endometrial stromal sarcoma with DNA flow cytometric analysis.

A case of a primarily extra-uterine low-grade endometrial stromal sarcoma is described. The patients clinical course, including various surgical, chemotherapeutical and hormonal therapies, is outlined and discussed. Transition from benign endometriosis to clinically malignant endometrial stromal sarcoma is illustrated by microscopy and DNA flow cytometry. A change in nuclear DNA content is demonstrated. This is possibly a useful aid in identifying the malignant potential of this tumor with such a misleading microscopic appearance.

Adult↗
PubMed1992

Intrathecal administration of etoposide in the treatment of malignant meningitis: feasibility and pharmacokinetic data.

Two patients presenting with malignant meningitis resulting from small-cell carcinoma of the lung and with lymphoblastic leukemia, respectively, were treated by intrathecal administration of etoposide. In both cases, this treatment was well tolerated and produced relief of the central nervous system symptoms. Pharmacokinetic data showed that cerebrospinal fluid drug levels of up to 5.2 micrograms/ml were achieved, which were considerably higher than those obtained after i.v. administration of high-dose etoposide.

Adult↗
PubMed1992

Phase II study of ACNU as second-line treatment in small-cell lung cancer. EORTC Lung Cancer Cooperative Group.

A total of 24 patients presenting with small-cell lung cancer either resistant to or relapsing within 3 months after first-line treatment were entered in a phase II study of 1-(4-amino-2-methyl-5-pyrimidinyl)-methyl-(2-chloroethyl)-3- nitrosourea hydrochloride (ACNU). ACNU was given i.v. at a dose of 75 mg/m2 every 6 weeks. We observed a partial response of 7 months' duration in one patient and one case of stable disease that lasted for 6 months; all other subjects exhibited progressive disease. Two patients developed brain metastases during treatment. The toxicity of ACNU consisted mainly of bone marrow suppression, especially thrombocytopenia. At this dose and on this schedule, ACNU shows minimal activity as second-line treatment in small-cell lung cancer.

Carcinoma, Small Cell↗
PubMed1992

Evaluation of tissue polypeptide antigen serum levels for monitoring disease activity during chemotherapy in patients with transitional carcinoma of the urinary tract.

In 28 patients with transitional carcinoma of the urinary tract, all treated with chemotherapy, serial measurements of serum tissue polypeptide antigen (TPA) were performed and correlated to clinical evaluations of response. At the start of chemotherapy elevated levels of TPA were found in 4 out of 14 patients with T2-4NO-2MO tumours and in 7 out of 14 patients with distant metastases. In most patients with elevated TPA levels who responded to chemotherapy, TPA levels rapidly returned to normal. False positive elevations of TPA were observed in 2 patients. It is concluded that serial measurement of TPA for monitoring disease activity has limited value because of the low sensitivity of TPA, especially for patients with early-stage cancer, and because of the occurrence of false positive results.

Adult↗
PubMed1992

Comparison of two carboplatin-containing regimens with standard chemotherapy for small cell lung cancer in a randomised phase II study. The EORTC Lung Cancer Cooperative group.

The EORTC Lung Cancer Cooperative group performed a randomised phase II study in patients with small cell lung cancer comparing the standard cyclophosphamide/doxorubicin/etoposide (CDE) regimen with two regimens containing the new and active cisplatin derivative, carboplatin, 400 mg/m2 in combination with ifosfamide, a drug without important myelotoxicity, at a dose of 5 g/m2 (IMP) or the non-myelotoxic drug vincristine twice 2 mg (VP). Of 178 evaluable patients, 63 received CDE [30 limited disease (LD), 33 extensive disease (ED)], 55 received IMP (22 LD, 33 ED) and 60 (26 LD, 34 ED) were treated with VP. The response duration was not statistically different: CDE 31 weeks, IMP 29 weeks and VP 21 weeks. The time to progression after CEE was 28 weeks, IMP 24 weeks and VP 17 weeks. This was significantly shorter after VP than after CDE (P = 0.017). The 60% response rate of the VP combination was low compared with CDE (83%) and IMP (77%). Toxicity of all three regimens was acceptable, and dose reduction for myelosuppression was necessary in only a minority of the patients. We conclude from this study that the combination of carboplatin, at the maximally tolerated dose of 400 mg/m2, in combination with ifosfamide 5 g/m2, is an active regimen with efficacy comparable with the standard CDE regimen.

Adult↗
PubMed1992

A phase I study of local treatment of liver metastases with recombinant tumour necrosis factor.

15 patients with therapy-resistant liver metastases were treated in a phase I study with recombinant tumour necrosis factor (rTNF). rTNF was injected into a liver metastasis by ultrasound guidance, using a 50 micrograms escalating dose schedule (3 patients/dosage) ranging from 100 to 350 micrograms per injection. Influenza-like symptoms such as fever, chills, nausea and vomiting were the main clinical side-effects. 2 patients experienced transient hypotension, probably due to concomitant use of morphine. Other toxicities, as reported after systemic use of rTNF, such as decrease in leucocytes and platelet counts, renal or liver toxicity were not observed. No difference was seen in subpopulations of lymphocytes (CD3+, CD4+, CD8+, CD16+ and CD19+) prior to and after rTNF injection. In 8 patients stable disease occurred in rTNF-treated metastases. The maximal dose used by this route of administration is 350 micrograms per injection. Based on these observations we conclude that the toxicity of rTNF injected into liver metastases by sonographic control is transient and mild. The results suggest that intratumoral administration of rTNF might play a role in local tumour control.

Adenocarcinoma↗
PubMed1992

A European Organization for Research and Treatment of Cancer--Genitourinary Group phase 2 study of chemotherapy in stage T3-4N0-XM0 transitional cell cancer of the bladder: evaluation of clinical response.

From 1986 to 1990 the European Organization for Research and Treatment of Cancer--Genitourinary Group conducted a phase 2 trial of neoadjuvant chemotherapy in patients with stage T3-4N0-XM0 transitional cell carcinoma of the bladder. The objectives were to evaluate the clinical response in relation to the pathological response, and to measure the side effects of chemotherapy. Of 171 patients entered 136 were fully evaluable: 18% had clinical complete remissions, 36% had clinical partial remissions, 39% had no clinical remissions and 10% had unknown response. A selected subgroup of 76 patients underwent cystectomy after 2 or 4 courses of chemotherapy: 2 were not evaluable for pathological response because of preoperative radiotherapy after neoadjuvant chemotherapy, 16 had a pathological complete remission, 7 had a pathological partial remission and 51 had no pathological remission. Comparison of the clinical response or T category only after 2 courses of chemotherapy with the pathological response after 2 or 4 courses of chemotherapy showed that in a number of patients the disease status could be downstaged to pathological complete or partial remission by additional courses of chemotherapy. If the discrepancies between clinical and pathological responses, or between T and P categories, induced by further downstaging after additional chemotherapy were left out, it was shown that clinical complete and partial remissions were a heterogeneous group but nonresponders could be delineated with a 100% accuracy by clinical response evaluation and transurethral resection biopsy only. Furthermore it seems important to establish the number of chemotherapy courses to induce a maximal response of the primary tumor.

Adult↗
PubMed1992

The prognostic value of the pathological response to combination chemotherapy before cystectomy in patients with invasive bladder cancer. European Organization for Research on Treatment of Cancer--Genitourinary Group.

The prognostic value of the pathological response to combination chemotherapy of deeply invasive transitional cell cancer of the bladder was retrospectively assessed in 147 patients. Data were collected from 8 different centers. Patients were eligible if they had received intravenous combination chemotherapy followed by partial, total or radical cystectomy, and if they had a minimum followup of 2 years after the start of chemotherapy. Of the patients 90% received methotrexate, vinblastine, doxorubicin and cisplatin (M-VAC) or cisplatin plus methotrexate for a median of 3 courses (range 1 to 6). Of the 83 patients who were alive at analysis actuarial median followup was 30.5 months (range 13.2 to 85.6 months). A major pathological response (stage P0, Pis, Pa or P1) was achieved in 41.5% of the patients. Patients with a major pathological response (p stage less than 2) had a 5-year survival of 75% in contrast to 20% for the remaining nonresponding patients (p stage 2 or more). The survival of patients with a major pathological response was independent of whether the response was induced by 2 or more courses of chemotherapy, or whether it was induced by M-VAC in comparison with cisplatin plus methotrexate. Preoperative clinical assessments can identify nonresponding patients correctly and in these cases alternative treatment programs are required, since 80% will die of the disease. Moreover, if neoadjuvant chemotherapy is proved to increase survival, the data emphasize the importance of the response rate of the primary tumor and the need to investigate the optimal number of courses to induce the best response, preferably in the individual patient.

Actuarial Analysis↗
PubMed1992

Distinction of two different classes of small-cell lung cancer cell lines by enzymatically inactive neuron-specific enolase.

Neuron specific enolase (NSE) is widely used as a neuro-endocrine marker. However the presence of NSE in many non-neuroendocrine tissues has raised questions on the specificity of NSE. We have investigated NSE immunoreactivity (NSA-ag), gamma-enolase activity and total enolase activity in small cell lung cancer (SCLC) cell lines. During well-controlled exponential growth comparison of NSE-ag content and gamma-enolase activity with the doubling-time (Td) and NSE-ag content with gamma-enolase and total enolase activity led to a clear distinction of two types of cell line: variant cell lines plus part of the classic cell lines (type I) and the remaining classic cell lines (type II). The distinction was based upon both an abrupt 6-fold increase of gamma-enolase activity and an 18-fold increase of NSE-ag, which for the larger part was enzymatically inactive. Within each group the increase of NSE-ag content was significantly correlated with the increase of gamma-enolase activity and both NSE-ag content and gamma-enolase activity increased linearly with Td. It is concluded that gamma-enolase seems to be associated with the regulation of growth rate and that a compound with the gamma-enolase antigen but without enzyme activity can distinguish two different classes of SCLC cell lines. Furthermore the demonstration that NSE-ag can represent the active enzyme as well as an enzymatically inactive compound may explain why a controversy about neuron- or non-specificity of NSE exists.

Carcinoma, Small Cell↗
PubMed1992

Cachexia and cancer: a clinician's view.

The cancer-related cachexia/anorexia syndrome is not well understood. It is related to several factors like metabolic changes, tumor types, and disease extent and is frequently accompanied by decreased performance status. An important aspect of anorexia is the psychosocial problem: the patient is unable to join the family for meals precisely when he or she most needs familial support. Several randomized studies have shown that megestrol acetate, possibly in a dose-dependent fashion, can improve appetite and lead to weight gain. This effect seems to be most prevalent in patients with breast cancer and also occurs in the absence of a tumor response. We have retrospectively analyzed 176 patients with cancer types other than breast cancer who received only palliative treatment. The patients were treated with megestrol acetate (160 mg tid) because they complained of anorexia. After 10 days of treatment, megestrol acetate was continued only in those patients whose appetite and/or general well-being improved. Fifty-seven patients (32%) experienced such an improvement and asked for continuation of therapy. Many basic questions are still unanswered; nonetheless, from a practical clinical view it seems worthwhile to offer anorectic patients a chance to improve, especially since side effects of megestrol acetate are absent or mild, and the distinction between responders and nonresponders can be made by 10 days of treatment.

Anorexia↗
PubMed1992

Therapy for small cell and non-small cell lung cancer.

This review addresses means for improving treatment results in small cell and non-small cell lung cancer. In small cell lung cancer lactate dehydrogenase and neuron-specific enolase seem to be important prognostic factors that may reflect not only tumor load but also growth rate. Chemotherapy seems to induce or select differentiated cells in small cell lung cancer, which focuses attention on other treatment modalities such as drugs, which can induce terminally differentiated nonproliferating cells. Scheduling of chemotherapy may improve survival, especially in extensive disease patients. Exciting new techniques for tumor targeting by a radiolabelled somatostatin-analogue and radiolabelled murine anti-epidermal growth factor are reported. The possible adverse effect of heterologous blood transfusions on survival after surgery of stage I and II non-small cell lung cancer remains a very important subject for investigation to solve the essential question whether the need for transfusion or the transfusion itself is the adverse prognostic factor. A possible improvement of survival of non-small cell lung cancer patients by chemotherapy should be investigated in patients with an excellent performance score and a small tumor load, eg, stage IIIa and IIIb patients. Neoadjuvant chemotherapy in such patients may improve survival but a better and especially more uniform design of the trials is urgently needed. Finally, the development of techniques to palliate terminally ill patients quickly and easily by reopening a closed bronchial lumen should be encouraged.

Carcinoma, Non-Small-Cell Lung↗
PubMed1992

Multicenter phase II study of spiroplatin.

Spiroplatin was investigated in a multicenter phase II study, during which the drug was given over 4 h. 64 Patients with nine different solid tumors received 141 cycles of spiroplatin at a dose of 30 mg/m2 every 3 weeks. Most important side effects included nausea, vomiting, myelosuppression, and renal toxicity. Four of 11 evaluable patients with prior cisplatin developed increases in serum creatinine (3 transient, 1 died of renal failure). Of 51 patients without prior cisplatin 2 had a transient increase in serum creatinine levels, and 2 showed persistent changes, in 1 of them leading to hemodialysis. Pre- and posthydration did not reduce drug-induced nephrotoxicity. Only 3 patients showed a response; 1 with renal cell carcinoma, 1 with ovarian carcinoma, and 1 with malignant melanoma. Based on the absence of striking antitumor activity and on the presence of severe unpredictable renal toxicity, the study was stopped prematurely.

Antineoplastic Agents↗
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↗