Search PubMed⌕ Search

Biomedical subjects

D Schrijvers

Publications and source records attributed to D Schrijvers.

At least 37 records · Page 2Linked to original sources
PubMed1999

KW-2149-induced pulmonary toxicity is not prevented by corticosteroids: a phase I and pharmacokinetic study.

KW-2149 is a new, semisynthetic, C-7-N-Substituted, mitomycin C analog showing antitumor activity both in vitro and in vivo, equal or superior to mitomycin C. In a phase I study, KW-2149 was administered as an i.v. bolus injection every 21 days and at a dose of 100 mg/m2 pulmonary toxicity was dose limiting. Animal studies have indicated since that KW-2149-induced pulmonary toxicity can be prevented by pretreatment with corticosteroids. This paper presents the results of a further phase I study of KW-2149 with corticosteroid pretreatment. Patients were treated with oral dexamethasone 8 mg every 12 h, starting 24 h before KW-2149 administration, for 5 days. KW-2149 was given as an i.v. bolus injection every 21 days. Seventeen patients were treated with a total of 48 courses. Six patients received 60 mg/m2 and 11 patients 75 mg/m2. Two courses were not evaluable for toxicity. Significant lung toxicity was observed in at least three patients treated with a dose of 75 mg/m2 KW-2149 and pulmonary toxicity was therefore considered the dose-limiting toxicity at 75 mg/m2. No other important side effects were noted. One partial response was observed in a patient with colorectal cancer. Pretreatment with dexamethasone failed to suppress KW-2149-induced lung toxicity.

Adrenal Cortex Hormones↗
PubMed1999

Rebound thymic hyperplasia after chemotherapy in a patient treated for pulmonary metastases.

A 38-year-old patient presented with an anterior mediastinal mass after chemotherapeutic and surgical treatment for lung metastases from a malignant histiocytoma. Because of the risk for tumour recurrence the thymic mass was resected. Thymic hyperplasia was found on pathological examination. In this case thymic hyperplasia is a rebound phenomenon aflcer chemotherapy. It appears to atrophy during the administration of chemotherapy and regrow afterwards. Surgical resection provides the definitive diagnosis and treatment.

Adult↗
PubMed1998

Pulmonary embolism.

Explore the source record for details and available documents.

Fibrinolytic Agents↗
PubMed1998

Late peritoneal metastasis in a patient with osteosarcoma.

A 19-year-old man with a high-grade osteosarcoma of the femur, treated with neoadjuvant chemotherapy, surgery, and adjuvant chemotherapy suffered from lung metastases 15 months after diagnosis. They were resected. Thirteen months later, he had vague abdominal complaints which, after analysis, proved to be caused by peritoneal metastasis. A review of the literature, possible physiopathological mechanisms of increased occurrence of unusual metastases and the role of bone scintigraphy in the follow-up of patients with osteosarcoma are discussed.

Adult↗
PubMed1998

Phase I study on docetaxel and ifosfamide in patients with advanced solid tumours.

Docetaxel and ifosfamide have shown significant activity against a variety of solid tumours. This prompted a phase I trial on the combination of these drugs. This phase I study was performed to assess the feasibility of the combination, to determine the maximum tolerated dose (MTD) and the side effects, and to propose a safe schedule for further phase II studies. A total of 34 patients with a histologically confirmed solid tumour, who were not pretreated with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-h infusion followed by ifosfamide as a 24-h infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg m(-2) and ifosfamide doses from 2.5 to 5.0 g m(-2). Granulocytopenia grade 3 and 4 were common (89%), short lasting and ifosfamide dose dependent. Febrile neutropenia and sepsis occurred in 17% and 2% of courses respectively. Non-haematological toxicities were mild to moderate and included alopecia, nausea, vomiting, mucositis, diarrhoea, sensory neuropathy, skin and nail toxicity and oedema. There did not appear to be any pharmacokinetic interaction between docetaxel and ifosfamide. One complete response (CR) (soft tissue sarcoma) and two partial responses (PRs) were documented. A dose of 75 mg m(-2) of docetaxel combined with 5.0 g m(-2) ifosfamide appeared to be manageable. Schedule A was advocated for further treatment.

Adult↗
PubMed1998

Determination of compatibility and stability of drugs used in palliative care.

BACKGROUND: Drugs for symptom control in the terminal phase of palliative patients may be used in pump systems. OBJECTIVE: To investigate the compatibility and stability of solutions of morphine hydrochloride, haloperidol, metoclopramide hydrochloride, atropine sulphate, butylhyoscine bromide and ranitidine hydrochloride, which may be used together under such circumstances. METHOD: Solutions of the drugs were exposed to ambient light at a temperature of 20 +/- 5 degrees C and +/- 31 degrees C for 24 h and 7 days and the solutions studied by ultraviolet spectrophotometry. RESULTS: The combination of haloperidol or metoclopramide hydrochloride with different concentrations of morphine hydrochloride seemed to be compatible and stable. The concentration of atropine sulphate or butylhyoscine bromide could not be determined by the study method, but morphine hydrochloride seemed to be stable. The combination of ranitidine hydrochloride and morphine hydrochloride showed a change in colour after 7 days. CONCLUSION: The results suggest that the combination of different concentrations of morphine hydrochloride with haloperidol, metoclopramide hydrochloride, atropine sulphate, butylhyoscine bromide or ranitidine hydrochloride do not affect their stability when stored for 7 days up to 30 degrees C under the influence of ambient light. However, more robust stability-indicating methods are required to confirm these results. The proposed method is more useful for identifying combinations that are clearly incompatible than to identify those that are compatible.

Atropine↗
PubMed1998

Update on the taxoids and other new agents in head and neck cancer therapy.

Both paclitaxel and docetaxel have shown activity when used as a single agent in patients with squamous cell carcinoma of the head and neck (SCCHN). Combinations of both drugs with platinum derivatives and antimetabolites have been tested in patient populations with encouraging results, but some have exhibited considerable toxicity. It is unknown as yet whether such combinations are in any way superior to the standard platinum-based regimens. Intensive weekly schemes of taxoids and platinum compounds alone or in combination seem possible and deserve further study. Other agents such as vinorelbine, ifosfamide, thymetaq, trimetrexate, gemcitabine and topotecan showed variable activity in patients with SCCHN, but their role is still questionable. Following the optimistic view on the role of chemoradiation, combinations of paclitaxel (with or without carboplatin) with radiotherapy were studied, and the results seem feasible and promising.

Adjuvants, Immunologic↗
PubMed1998

Phase III trial of modulation of cisplatin/fluorouracil chemotherapy by interferon alfa-2b in patients with recurrent or metastatic head and neck cancer. Head and Neck Interferon Cooperative Study Group.

PURPOSE: In preclinical experiments, interferon alfa modulates the anticancer activity of fluorouracil (5-FU) and cisplatin (CDDP). To test this effect clinically in patients with recurrent or metastatic head and neck cancer (RMHNC), a multicenter randomized controlled trial with CDDP and 5-FU with or without interferon alfa-2b (IFNalpha) was performed. PATIENTS AND METHODS: Eligible patients had histologically confirmed RMHNC; a good performance status; measurable disease; adequate bone marrow, hepatic, and renal function; no prior chemotherapy for recurrent or metastatic disease; only one chemotherapy regimen administered with previous local therapy; and a treatment-free interval of at least 3 months following previous local therapy. Patients were randomized and stratified according to treatment center, and prior radiotherapy and chemotherapy. The treatment regimen consisted of CDDP 100 mg/m2 on day 1 and 5-FU 1,000 mg/m2/d by continuous infusion for 96 hours (days 1 to 4), without (arm A) or with (arm B) IFNg alpha 3 x 10(6) U/d subcutaneously on days 1 to 5. Cycles were repeated every 21 days. RESULTS: One hundred twenty-two patients were entered on each arm. The response rate (RR) was similar in both arms (arm A: complete response [CR] 10.7%, partial response [PR] 36.4%; arm B: CR 6.8%, PR 31.6%) (.70 < P < .50). There was no difference in median survival between the two arms (arm A 6.3 months v arm B 6.0 months; P = .49). Anorexia, fever, leukopenia, and thrombocytopenia grade III to IV were significantly more frequent in the IFNalpha arm. CONCLUSION: Modulation of CDDP and 5-FU with IFNalpha as used in this study does not improve the RR or the median survival in patients with RMHNC. Patients on both study arms had a poor prognosis, which indicates the need for novel therapies.

Adult↗
PubMed1998

Docetaxel and ifosfamide in patients with advanced solid tumors: results of a phase I study.

Docetaxel is a new antimicrotubule agent that has been shown to be active against a variety of solid tumors. Ifosfamide is an alkylating drug that has demonstrated activity against non-small cell lung cancer, testicular cancer, breast cancer, and soft tissue sarcoma. This phase I study of the combination of these drugs was performed to assess the feasibility of using the two agents together, to determine the maximum tolerated dose and the side effects, and to propose a safe schedule for further phase II studies. Thirty-four patients with histologically confirmed solid tumors who had not been treated previously with taxanes or ifosfamide and who had received no more than one line of chemotherapy for advanced disease were entered into the study. Treatment consisted of docetaxel given as a 1-hour infusion followed by ifosfamide as a 24-hour infusion (schedule A), or ifosfamide followed by docetaxel (schedule B) every 3 weeks. Docetaxel doses ranged from 60 to 85 mg/m2 and ifosfamide doses from 2.5 to 5.0 g/m2. Grades 3 and 4 granulocytopenia were observed in 89% of courses and appeared to be of short duration and related to the ifosfamide dose. Febrile neutropenia and sepsis occurred in 17% and 2% of courses, respectively. Severe anemia and thrombocytopenia were uncommon. Nonhematologic toxicities were mild to moderate, and included alopecia, nausea, vomiting, mucositis, diarrhea, sensory neuropathy, skin and nail toxicity, hypersensitivity reactions, and edema. Schedule B appeared to induce more gastrointestinal toxicity than schedule A. One complete response in soft tissue sarcoma and two partial responses, one in cancer of unknown primary and the other in non-small cell lung cancer, were documented. The dose-limiting toxicity for schedule A was neutropenic fever at a dose of 85 mg/m2 docetaxel and 5 g/m2 ifosfamide. The dose-limiting toxicity for schedule B was neutropenic fever at a dose of 75 mg/m2 docetaxel and 4 g/m2 ifosfamide. A dose of 75 mg/m2 docetaxel combined with 5 g/m2 ifosfamide according to schedule A can be recommended for further studies.

Adult↗
PubMed1997

Ongoing trials in patients with head and neck cancer.

Treatment of squamous cell carcinoma of the head and neck has recently undergone several important changes. New approaches to treating these tumours are now being evaluated. An overview of the surgical, radiotherapeutic and chemotherapeutic therapies or multimodality approaches currently under study are described. In addition, the design of ongoing chemoprevention trials is reported.

Carcinoma, Squamous Cell↗
PubMed1997

Activated oxazaphosphorines are transported predominantly by erythrocytes.

PURPOSE: Oxazaphosphorines are metabolised by a variety of pathways, one of which leads to activation and the formation of alkylating compounds. However, the transport forms conveying activated oxazaphosphorines to the tumour cell have not been fully characterised. There is increasing recognition of the importance of the erythrocyte as a carrier of compounds in the circulation, and we have recently described higher concentrations of 4-hydroxycyclophosphamide within the erythrocyte compartment compared to plasma. We have now determined the concentrations of ifosfamide and seven of its metabolites in the plasma and erythrocytes of patients receiving a six-hour intravenous infusion of ifosfamide. PATIENTS AND METHODS: Red cells from five patients, receiving a total of eight cycles of ifosfamide, were separated from plasma using the MESED instrument, and analysis of red cells and plasma performed using Gas Chromatography-Mass Spectrometry (GC/MS). RESULTS: The concentration of all compounds in the erythrocyte compartment was higher than or equal to those in plasma, and isophosphoramide mustard and carboxyifosfamide showed a particular affinity for the erythrocyte. The red cell fraction can contain as much as 77% of the total blood concentration of isophosphoramide mustard. CONCLUSIONS: Erythrocyte associated isophosphoramide mustard is an important transport form of activated ifosfamide. Red cells may have a role in the delivery of activated oxazaphosphorines to tissues.

Antineoplastic Agents, Alkylating↗
PubMed1997

Role of hepatic arterial embolisation in the treatment for metastatic insulinoma. Report of two cases and review of the literature.

Malignant insulinomas are very rare. They have typical clinical and biochemical characteristics that allow an early detection and distinction from other sorts of islet cell carcinoma. As a result a curative resection can occasionally be managed. Nevertheless, for more advanced stages the same treatment options as for other metastatic neuroendocrine tumours must be considered: palliative surgery, medical treatment, chemotherapy and hepatic arterial (chemo-) embolisation. Especially the last kind of treatment has recently gained interest. We report two cases of metastatic insulinoma treated in this way. In the first case we are able to record an unusually long survival through the single use of sequential embolisation, following palliative resection of the primary tumour. In the second case we describe the current way to use this technique, i.e. in combination with chemotherapy. We argue that it might be more important in the treatment of metastatic insulinoma to combine hepatic arterial embolisation with other types of local or systemic therapy, rather than the choice of this most efficient technique on its own.

Adult↗
PubMed1997

Botryomycosis mimicking a liposarcoma.

Botryomycosis is an atypical reaction of the host to a common bacterial infection. A case of botryomycosis mimicking a liposarcoma as suspected on clinical and radiological grounds is described. The diagnosis was made by biopsy and culture of the lesion. A review of the literature is given.

Abdomen↗