Biomedical subjects
J Verweij
Publications and source records attributed to J Verweij.
Phase II study on oral N-methylformamide in metastatic colorectal cancer.
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[Microangiopathic hemolytic anemia and metastasized carcinoma].
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The difference in pharmacokinetics of mitomycin C, given either as a single agent or as a part of combination chemotherapy.
In a previous report it was suggested that the total body clearance of mitomycin C (MMC) was different after single agent treatment compared to combination chemotherapy. This suggestion was based on recalculations to one dose level. In the present study a fixed dose of 10 mg/m2 was used. Seven patients on single agent MMC and eight on combination chemotherapy were studied. Terminal half-life varied from 25 to 78 mm, volume of distribution from 7 to 73 l/m2, total body clearance from 11 to 56 l/h per m2, and area under the plasma concentration-time curve (AUC) from 177 to 933 micrograms/h per l. Total body clearance was significantly higher and AUC significantly lower in patients on combination chemotherapy. The cause of this difference was not investigated.
The treatment of soft tissue sarcomas with focus on chemotherapy: a review.
Radical surgery remains the most effective treatment of soft tissue sarcomas. The postoperative addition of radiotherapy appears to reduce local recurrence in extremity lesions. To date, there are still only two drugs with major activity as a single agent in the treatment of soft tissue sarcomas: doxorubicin (DX) and ifosfamide (IFX). Doxorubicin should be administered preferably as 3-weekly bolus injections at doses higher than 60 mg/m2 because of its dose-response relationship. In combination chemotherapy ADIC and CYVADIC are probably the best choice. Although there are no definite data on increased activity with the addition of cyclophosphamide (CTX) and vincristine (VCR) to ADIC, we prefer CYVADIC because of the higher reported complete response rate. A limited number of patients with soft tissue sarcomas achieving a complete response with chemotherapy, will probably be cured, and for this reason it is important to aim at achieving a complete response. Preoperative intraarterial chemotherapy in locally advanced soft tissue sarcomas may further improve survival results, but before definite conclusions can be drawn, this technique should be investigated in randomized studies. Postoperative adjuvant chemotherapy should still be considered investigational, as no advantage has been observed in head, neck and trunk lesions, while data on extremity lesions are still conflicting.
Comparison of three methods for measuring central venous pressure.
We used a digital display value, a recorded pressure curve, and manometric measurements to determine CVP in 35 ICU patients who had either a central venous line or a pulmonary artery catheter. CVP was measured by each method up to five times per patient, for a total of 107 data sets. Display values compared well to those from the recorded pressure curve. Manometric measurements, however, poorly matched electronically determined values. Factors influencing these results are discussed.
The absence of influence of acetylsalicylic acid (ASA) on the transient decrease in platelet counts observed after infusion of bleomycin and vinblastine.
Retrospectively we observed an early-onset transient decrease in platelet counts in a group of patients treated with cisplatin, vinblastine and bleomycin. Though less pronounced, the decrease was also found in a prospectively studied group of patients treated with bleomycin, etoposide and cisplatin, but was absent after treatment with etoposide ad cisplatin. In a randomized cross-over study acetylsalicylic acid (ASA) appeared not to prevent the drop in platelet counts. Bleomycin appears to induce an early-onset transient decrease in platelet numbers, possibly by direct or indirect platelet lysis. Vinblastine may have a synergistic effect to this phenomenon.
Primary tracheo-bronchial melanoma.
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Cisplatin-based chemotherapy in advanced adenoid cystic carcinoma of the head and neck.
Nineteen patients, nine men and 10 women, with advanced adenoid cystic carcinoma (ACC), were treated with cisplatin either alone or in combination with doxorubicin and bleomycin. Median age was 51 years (range: 32-73 years). Two groups of patients were distinguished: Group 1 (N = 10) received single-agent cisplatin (50-120 mg/m2 IV every 4 weeks) for locoregional recurrence (N = 4), pulmonary metastases (N = 5), or as neoadjuvant therapy (N = 1). Five patients failed previous chemotherapy. No objective responses were observed, five patients showed stabilization of their disease for a median duration of 20 months (range: 3-50 months). Group 2 (N = 9) received a combination of cisplatin (20 mg/m2 IV on days 1-5), doxorubicin (50 mg/m2 IV on day 1), and bleomycin (30 mg IV on days 1-5), every 3 weeks. A complete remission (CR) was seen in one patient, lasting for 2 years, a partial remission (PR) in two patients (duration: 6 months and 6 years) (33%), and a stable disease (SD) in five patients (median duration: 15 months; range 3-24 months). One patient showed progression from the start. The observed toxicity was acceptable: dose reduction was required in five patients for myelosuppression or impairment of renal function; vomiting grade III (WHO) was seen in 10 patients. The median progression-free survival was 36 months (range: 7-77 months). Median overall survival was 81 months (range: 14-216 months). The role of cisplatin in this disease remains questionable.
GABA sensitivity of spectrally classified horizontal cells in goldfish retina.
We studied the GABA sensitivity of horizontal cells in the isolated goldfish retina. After the glutamatergic input to the horizontal cells was blocked with DNQX, GABA depolarized the monophasic and biphasic horizontal cells. The pharmacology of these GABA-induced depolarizations was tested with the GABA receptor antagonists bicuculline-methiodide and picrotoxin, the GABA transporter agonist nipecotic acid, and the GABA transporter antagonist SKF 89976-A. The GABA-induced responses of monophasic horizontal cells consisted of two components; one with characteristics of GABA-gated chloride channels, and one with characteristics of GABA transporters. In biphasic horizontal cells, we only found evidence for GABA-gated chloride channels. The results show that monophasic horizontal cells in goldfish contain the two components of a positive feedback loop (GABA transporters and GABA-gated chloride channels), as described in salamander. Furthermore, our results indicate that the monophasic horizontal cells may project directly to the biphasic horizontal cells, via an excitatory GABAergic pathway. We propose that the function of these GABAergic systems in horizontal cells is to abolish cone dominance in bipolar cells surround in the dark-adapted retina.
Phase II study of ACNU as first-line treatment in advanced colorectal cancer.
Thirty-two patients with metastatic colorectal cancer were entered in a phase II study of ACNU as first-line treatment. ACNU was given at a dose of 100 mg/m2 i.v. every six weeks. In 30 evaluable patients we observed partial responses lasting 5 and 8 months in 2 patients with liver metastases, and stable disease in 4 patients. The toxicity mainly consisted of leuco- and trombocytopenia. We conclude that in this dose and schedule ACNU has only very limited activity in metastatic colorectal cancer.
What is the role of dose-dense therapy?
The introduction of paclitaxel/platinum combination chemotherapy and (interval) debulking surgery has significantly improved the prognosis of patients with ovarian cancer. Yet, many patients die of drug-resistant disease. Second-line chemotherapy may result in prolonged secondary remissions with alleviation of symptoms and improvement of quality of life. The response to second-line chemotherapy is strongly related to platinum sensitivity. More than 60% of platinum-sensitive patients respond to a re-challenge with platinum-containing chemotherapy. In platinum-resistant patients, on the contrary, the response rate to a re-challenge with 3-weekly platinum or any nonplatinum chemotherapy is less than 20%. The response to dose-dense weekly platinum-based regimens ranged from 48% to 64% in platinum-resistant patients. Moreover, the majority of the patients responded within 8 weeks after the start of the treatment. The progression-free survival ranged from a median of 5 months in a study using cisplatin/etoposide, to 11 months in a study with paclitaxel/carboplatin. The median survival was 11-15 months. The outpatient weekly paclitaxel/carboplatin regimen, with paclitaxel at a dose of 90 mg/m(2) and carboplatin at area under the curve 4, seems similarly effective and is better tolerated. Dose-dense weekly paclitaxel/carboplatin is an effective and well-tolerated therapy for platinum-sensitive, as well as platinum-resistant tumors. Responses to therapy are observed within 8 weeks in the majority of the patients. Whether a weekly regimen indeed is more effective than 3-weekly paclitaxel/carboplatin needs to be answered in a randomized study.