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Biomedical subjects

P E Postmus

Publications and source records attributed to P E Postmus.

At least 19 recordsLinked to original sources
PubMed1992

[2 patients with brain metastases who became pregnant during phenytoin administration].

Two young women taking phenytoin because of symptomatic brain metastases are described. Both patients, one with end-stage lung cancer and the other in complete remission after intensive chemotherapeutic treatment of a choriocarcinoma, became pregnant while using oral contraceptives in combination with phenytoin. One patient had the child, but died a year after the metastases became apparent, in the other the pregnancy was terminated. When prescribing phenytoin, attention should be paid to fertility--even in patients with end-stage cancer or after intensive, possibly sterilising, chemotherapeutic treatment.

Abortion, Therapeutic↗
PubMed1992

In vitro response of human small-cell lung-cancer cell lines to chemotherapeutic drugs; no correlation with clinical data.

Three cell lines derived from small-cell lung carcinoma (SCLC) tumors of patients who had no clinical response after treatment with a multi-drug regimen were compared to 3 cell lines derived from tumors of patients who, upon treatment, showed a complete clinical response. These 2 groups of cell lines were considered to represent the in vitro counterparts of the 2 extremes of the clinical spectrum of sensitivity for chemotherapeutic drugs in small-cell lung cancer. To assess whether the in vivo (in)sensitivity of a tumor to a certain drug regimen is retained in vitro, the cell lines were tested for drug sensitivity using the microtiter-well tetrazolium assay and the results were compared with the in vivo data. No correlation was found. Since in vitro models using cell lines are based on the assumption that a cell line reflects the properties of the tumor from which it is derived, several additional parameters such as MAb staining against different SCLC-associated antigens and DNA content were analyzed in the biopsies and the cell lines. The results showed that selection of discrete tumor-cell populations in vitro occurs. Results of in vitro chemosensitivity testing for individual SCLC patients should be interpreted with caution.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Phase II study of high-dose epirubicin and etoposide in advanced non-small cell lung cancer.

25 consecutive patients with advanced non-small cell lung cancer (NSCLC) were treated with high-dose epirubicin (HDE) 135 mg/m2 and etoposide 60 mg/m2 (days 1-3) every 3 weeks. 121 courses, (median 6, range 1-7), were administered and evaluable for toxicity: WHO grades III/IV leukocytopenia in 60/36 (80%) courses, thrombocytopenia in 18/6 (20%) and grades II/III anaemia in 31/6 (31%). Median (range) left ventricular ejection fraction (LVEF) fell from 63% (53-73, n = 25) to 60% (48-73 n = 16) after 5 courses (P < 0.02). 2 patients had a drop of more than 15% in LVEF with an epirubicin dose of 675 mg/m2. Apart from 1 patient who had tachycardia 6 months after the last course, no patient had congestive heart failure. There were 2 complete and 7 partial responses [total 9/25 (36%, 95% confidence interval: 18-57.5%)]. Median survival is 31.8 (4.3-75) weeks. Combination HDE and etoposide in NSCLC offers no advantage over HDE alone and is more toxic.

Aged↗
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

Recombinant interferon alpha-2b in patients with metastatic apudomas: effect on tumours and tumour markers.

Malignant carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid are tumours with similar clinical features. In patients with unresectable or metastatic tumours leukocyte interferon (IFN) and recombinant human (rh) IFN have demonstrated efficacy. Twenty-four evaluable patients with progressive tumours were treated with 2.5 megaunits rh IFN alpha-2b, administered once daily subcutaneously, for a median duration of 7 months (range 0.5-37+). Two carcinoid patients demonstrated a response in tumour size, 80% showed stable disease (SD). Sixty percent of the carcinoid patients with elevated urinary 5-hydroxyindoleacetic (5-HIAA) levels reached a biochemical partial response of the urinary 5-HIAA levels (median duration 13.5 months). In the patients with an islet cell or medullary tumour and an elevated tumour marker, the marker did not further increase. Of the 12 carcinoid patients evaluable for a symptomatic response, ten (83%) experienced a relieve of symptoms. IFN alpha-2b dose reduction or discontinuation due to toxicity was necessary in three and ten patients, respectively. No neutralising IFN alpha-2b antibodies developed despite prolonged treatment. In conclusion, IFN alpha-2b had a beneficial effect in patients with progressive tumours, while long-term IFN alpha-2b treatment did not augment neutralising antibodies. In view of the IFN alpha-2b-related toxicity, administration of IFN alpha-2b on alternating days may be preferable.

Adenoma, Islet Cell↗
PubMed1992

A phase II study of high dose epirubicin in unresectable non small cell lung cancer.

Epirubicin (EPI), a doxorubicin analogue, is reported to have equal antitumour activity with lower cardiac and systemic toxicity. Recently, the maximum tolerated dose of this drug has been revised upwards with reported increased response rates in several malignancies. We initiated a phase II study of high-dose EPI as initial treatment for patients with advanced non-small cell lung cancer (NSCLC) (stage III and IV). Between May 1988 and November 1989, 25 patients were entered. The starting dose of EPI was 135 mg m-2, with dose attenuations and escalations of 15 mg m-2 based on mid-cycle evaluation of toxicity. Treatment was repeated every 3 weeks. Nine partial responses (36%, 95% CI: 18-57.5%) and 11 patients with disease stabilisation (44%) were observed. Median (range) time to progression was 19 (3-70) weeks. Median (range) survival is 32 (9-116+) weeks. There were no treatment related deaths. Major side effects were leukocytopenia WHO grade III/IV (23% of courses) and mucositis WHO grade II/III (15% of courses). In two patients left ventricular ejection fraction decreased greater than 15% compared to baseline values after a cumulative Epirubicin dose of 435 mg m-2, and therefore went off study. In none of the patients clinical signs of congestive heart failure were observed. We conclude from our data that high-dose EPI, contrary to previous negative studies using lower doses of EPI, ranks amongst the most active regimens against advanced NSCLC. Toxicity of high-dose EPI is moderate. Further evaluation of this compound in combination regimens is recommended.

Adult↗
PubMed1992

Effects of recombinant human interleukin-3 in patients with relapsed small-cell lung cancer treated with chemotherapy: a dose-finding study.

PURPOSE: The aim of the study was to determine the maximum tolerable dose of recombinant human interleukin-3 (rhIL-3) after combination chemotherapy and to evaluate the ability of rhIL-3 to influence hematopoietic recovery. PATIENTS AND METHODS: Nineteen patients who had relapsed small-cell lung cancer (SCLC) received rhIL-3 after their second course of chemotherapy, which consisted of either cyclophosphamide, doxorubicin, and etoposide (CDE) every 3 weeks or vincristine, ifosfamide, mesna, and carboplatin (VIMP) every 4 weeks. Twenty-four hours after the last chemotherapy dose, rhIL-3 was administered subcutaneously (SC) once daily for 14 days on an outpatient basis. Escalating dosages (1, 2, 4, 8, and 16 micrograms/kg/d) of rhIL-3 were tested. Hematologic effects were evaluated by comparing blood cell recovery after chemotherapy cycle 1 and cycle 2 plus rhIL-3. RESULTS: The adverse effects of rhIL-3 at dosages up to 8 micrograms/kg/d consisted mainly of low-grade fever and flulike symptoms. At 16 micrograms/kg, rhIL-3 headache became dose-limiting. Severe neutropenia (neutrophils less than 0.5 x 10(9)/L) after VIMP cycle 2 was shorter in duration than after cycle 1 (7 v 3 days; P less than .05). At rhIL-3 dose levels 8 and 16 micrograms/kg, hematologic effects in seven patients who were treated with VIMP showed a significant hastened recovery of leukocyte and neutrophil counts during cycle 2 compared with cycle 1 and increased monocyte and eosinophil counts in cycle 2 compared with cycle 1. rhIL-3 also increased reticulocyte and platelet counts at a dose level of 8 micrograms/kg. No significant stimulation of basophils and lymphocytes was observed. Apart from the hematologic effects, rhIL-3 also augmented the release of cytokines such as tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6), and lowered cholesterol levels. CONCLUSIONS: This study demonstrates that rhIL-3 can be safely administered after chemotherapy on an outpatient basis. rhIL-3 is tolerated well at doses up to 8 micrograms/kg/d and is biologically active in patients after myelosuppressive chemotherapy.

Adult↗
PubMed1992

Second-line carboplatin-based chemotherapy for small cell lung cancer: the Groningen experience.

In this report, the results of two phase II studies and one pilot study of second-line carboplatin-based chemotherapy for small cell lung cancer are described. Carboplatin plus vincristine given with or without ifosfamide resulted in response rates of 36% and 53%, respectively, in so-called chemotherapy-resistant patients. Toxicity of the carboplatin/vincristine regimen was mild (hematologic toxicity grade 4 was seen with 13% of the courses), whereas the combination including ifosfamide resulted in grade 4 thrombocytopenia in 57% of the courses and grade 4 leukocytopenia in 49%. A partial response was seen in one of nine patients with progression of brain metastases after chemotherapy, and in three patients the neurologic function score improved, with minor tumor reduction evident on computed tomography scan of the brain. We conclude that carboplatin is a useful agent for second-line chemotherapy in patients with an early relapse after induction chemotherapy.

Adult↗
PubMed1992

Phase I study of oral teniposide (VM-26).

A phase I study of teniposide administered orally for 5 consecutive days was performed. The first dose was 60 mg/m2/d, with increments of 25 mg/m2/d. Nineteen patients entered the study and received a total of 77 courses with a median of two (range, 1 to 12). Dose-limiting toxicity occurred at 160 mg/m2/d and consisted of myelosuppression, mainly leukocytopenia, and gastrointestinal toxicity. Sufficient recovery of blood counts was seen by day 21 to allow for a repeat course. Two patients, treated with teniposide doses of 110 and 160 mg/m2/d, respectively, were considered toxic deaths. Partial alopecia was frequent at doses above 85 mg/m2/d. Retching and vomiting during administration of the drug were encountered in virtually all patients. Oral teniposide 135 mg/m2/d for 5 consecutive days on a 3-week schedule is recommended for evaluation of antitumor efficacy in phase II studies.

Administration, Oral↗
PubMed1992

Treatment of brain metastases of small cell lung cancer with teniposide.

Over 50% of patients with small cell lung cancer (SCLC) will develop symptomatic brain metastases during the course of their disease. Results of whole brain radiotherapy, the standard treatment, are rather poor and relapses are frequent. Thus, new modes of therapy are urgently needed for these patients. In this study, the efficacy of teniposide was evaluated at a dose of 150 mg/m2 intravenously on days 1, 3, and 5 at 3-week intervals. In 11 of 26 evaluable patients an intracranial response was observed. Median response duration was 23 weeks (range, 9 to 50). Toxicity was acceptable, with grades 3/4 leukocytopenia and thrombocytopenia reported in 37% and 16%, respectively, of 123 courses. Therefore, teniposide is an effective agent against brain metastases of SCLC and is suitable for palliation of these patients.

Aged↗
PubMed1992

Improved diagnosis of carcinoid tumors by measurement of platelet serotonin.

Carcinoid patients are diagnosed biochemically on the basis of increased urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA); urinary and platelet serotonin concentrations are considered to provide complementary information. Using established HPLC methods with fluorometric detection, we evaluated the clinical usefulness of measurements of urinary 5-HIAA and urinary, plasma, and platelet serotonin in 30 consecutive patients with histologically proven carcinoid tumors of fore-, mid-, and hindgut origin before treatment. Ten patients showed no signs of serotonin overproduction; 14 had increased concentrations of urinary 5-HIAA and platelet serotonin; and platelet serotonin, but not urinary 5-HIAA, was increased in 6. None had increased urinary 5-HIAA excretion without an increase in platelet serotonin content. In cases with high rates of tumor serotonin secretion, platelet serotonin reached a maximum and did not correlate with serotonin secretion rate, whereas urinary 5-HIAA was correlated. Increased platelet serotonin was correlated with increased plasma serotonin and with occurrence of carcinoid syndrome. Increased urinary serotonin, allegedly caused by increases in circulating 5-hydroxytryptophan, almost invariably coincided with increased platelet serotonin, but not necessarily with above-normal urinary 5-HIAA excretion. From these results and long-term monitoring of three patients during treatment, we conclude that platelet serotonin is more sensitive than urinary 5-HIAA for detecting carcinoids that secrete only small amounts of serotonin.

Adolescent↗