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Biomedical subjects

C J Rodenburg

Publications and source records attributed to C J Rodenburg.

At least 19 recordsLinked to original sources
PubMed2006

Randomised study of sequential versus combination chemotherapy with capecitabine, irinotecan and oxaliplatin in advanced colorectal cancer, an interim safety analysis. A Dutch Colorectal Cancer Group (DCCG) phase III study.

BACKGROUND: Results on overall survival in randomised studies of mono- versus combination chemotherapy in advanced colorectal cancer patients may have been biased by an imbalance in salvage treatments. This is the first randomised study that evaluates sequential versus combination chemotherapy with a fluoropyrimidine, irinotecan and oxaliplatin. PATIENTS AND METHODS: A total of 820 patients were randomised between first-line capecitabine, second-line irinotecan and third-line capecitabine + oxaliplatin (arm A) versus first-line capecitabine + irinotecan, and second-line capecitabine + oxaliplatin (arm B). The primary end point was overall survival. We present the results of an interim analysis on the safety data in the first 400 patients. RESULTS: In first-line the incidence of grade 3-4 diarrhoea, nausea, vomiting and febrile neutropenia was significantly higher in arm B. However, when toxicity over all lines was considered only grade 3 hand-foot syndrome occurred more frequently in arm A (12% versus 6%, respectively, P = 0.041). The incidence of cardiovascular toxicity was low. In two out of five patients with sudden death (one in arm A, four in arm B) cardiovascular risk factors were present. CONCLUSIONS: Both treatment arms had an acceptable safety profile. These data imply that the results on survival will be the major determinant for the selection of either strategy. Capecitabine plus irinotecan appears to be a feasible first-line treatment for patients with advanced colorectal carcinoma.

Adult↗
PubMed2005

Discrepancy between second and first opinion in surgical oncological patients.

PURPOSE: To prospectively describe in a population of oncological second opinion patients: (1) the outcome of routine revisions of histopathological and radiological material, (2) the frequency and extent of discrepancy between the second and first opinion and (3) the location of further treatment or follow-up. PATIENTS AND METHODS: In a population of 466 consecutive patients seeking a second opinion at the Surgical Oncology Outpatient Clinic, demographic and clinical patient characteristics were registered prospectively, as were the results of routine revision of histopathological and radiological material and the location of further treatment or follow-up. A classification system was developed to categorize the differences between the second and first opinion. RESULTS: The mean age of the 403 eligible patients was 52 years. Most patients (87%) were women, of whom 83% were diagnosed with breast cancer. Revision of histopathological and radiological material was performed in 80 and 61% of the cases, respectively, and resulted in a major change in treatment or prognosis in 3 and 2% of patients, respectively. In 317 patients (79%), the second opinion could be compared with the first opinion, resulting in an identical advise in 68%, a minor discrepancy in 16% and a major discrepancy in another 16% of patients. For further treatment 78% of patients were referred back to their first specialist. CONCLUSION: One third of patient-initiated second opinion consultations resulted in a discrepancy with the first opinion. Half of these different advise lead to major changes in therapy or prognosis.

Adult↗
PubMed2004

A phase I dose-escalating study of docetaxel plus folinic acid and 5-fluorouracil in anthracycline-pretreated patients with metastatic breast cancer.

BACKGROUND: Since the need for nonanthracycline-containing chemotherapy regimens increases with the increased use of anthracyclines in earlier stages of breast cancer, we investigated the feasibility of the combination of docetaxel and 5-fluorouracil (5-FU) with folinic acid (FA). PATIENTS AND METHODS: Anthracycline-pretreated patients with metastatic breast cancer were eligible. Docetaxel was administered as a one-hour infusion every three weeks on day 1, FA 500 mg/m2 (fixed dose) as a two-hour infusion on days 1 and 15 and 5-FU as a 24-hour infusion on days 1 and 15. The dose levels tested were (docetaxel/5FU in mg/m2): 60/1800, 75/1800, 85/1800, 100/1800, and 100/2100. RESULTS: Altogether 28 patients were accrued and treated in this multicentre open-label study. Dose-limiting toxicities (DLTs) were not observed at dose level I, and in two patients in each of the higher dose levels. DLTs observed were grade III/IV infection (n=4), febrile neutropenia (n=2), diarrhoea (n=1) and erythema (n=1). Partial responses were observed in 10 out of 24 evaluable patients (42%, 95% confidence interval 22.1 to 63.4%). Dose escalation beyond the highest dose level (100/2100) was deemed inappropriate, because these dose levels correspond to recommended dose levels for each drug as a single agent. CONCLUSION: Combination of docetaxel (100 mg/m2, one-hour infusion q3 weeks on day 1), FA (500 mg/m2, two-hour infusion on days 1 and 15) and 5-FU (2100 mg/m2, 24-hour infusion on days 1 and 15) is a feasible regimen with encouraging activity in anthracycline-pretreated patients.

Adult↗
PubMed1998

[Taxoids in ovarian and breast carcinoma: the role of the medical profession and the government].

After registration in 1993/1995 of paclitaxel and docetaxel for the treatment of ovarian and mammary carcinomas, the costliness of these drugs caused Dutch hospitals to adopt different policies for their use. This prompted the Minister of Health to ask the professional group of oncological internists to draw up a guideline for the use of taxoids, following which the government decided to supply extra money for the hospitals to use according to this guideline. Meanwhile new, contradictory study results have become known, still unpublished and in part originating from studies not yet conclude. The pharmaceutical industry advocates terminating the current research and maintaining the existing indications. However, patients are entitled to unbiased, complete research findings. The pathway for introducing new expensive drugs should be as follows: the professionals determine the indications for the new drug, the government pays attention to the financial consequences. The pharmaceutical industries should have no voice in the relevant decision-making.

Antineoplastic Agents, Phytogenic↗
PubMed1996

Carcino-embryonic antigen--no help with the differential diagnosis.

Two patients who were referred because of an increase in serum carcino-embryonic antigen (CEA) were diagnosed after a number of years as having a medullary thyroid carcinoma. The relationship between CEA and medullary thyroid carcinoma is discussed. The serum level of CEA is neither sensitive nor specific enough to serve as a diagnostic tool. Its determination, however, is useful in the follow-up of patients with carcinoma of the breast, colo-rectal carcinoma and medullary thyroid carcinoma.

Aged↗
PubMed1994

The effects of an ACTH (4-9) analogue on development of cisplatin neuropathy in testicular cancer: a randomized trial.

The efficacy of the ACTH (4-9) analogue Org 2766 in the prevention of subclinical cisplatin neuropathy was assessed in a double-blind placebo-controlled multi-centre study in patients with testicular cancer or adenocarcinoma of unknown primary. Forty-two patients received at least four cycles of cisplatin (100 mg/m2 per cycle), together with subcutaneous injections of Org 2766 (2 mg/day for 5 consecutive days) or placebo. Vibratory threshold was used as a measure of neuropathy. For each individual patient, the influence of cisplatin on vibratory perception was quantified by the slope of the regression line between the natural logarithm of the vibratory thresholds and the number of cycles. From the slopes, the proportional increase of vibratory threshold per cycle of cisplatin was calculated. On average, vibratory thresholds increased by 42% with each cycle of 100 mg/m2 of cisplatin in the placebo group, and by 19% during treatment with Org 2766. The influence of cisplatin on vibratory thresholds was highly significant in the placebo group (P < 0.0001), and of borderline significance in the group treated with Org 2766 (P = 0.06). The difference in slopes between the two groups was of borderline statistical significance (Wilcoxon's two-sample test: P = 0.06; analysis of variance: P = 0.04). These results show that Org 2766 cannot completely prevent cisplatin neuropathy in young men with testicular cancer, but nerve damage may be ameliorated by the use of this ACTH (4-9) analogue.

Adenocarcinoma↗
PubMed1993

The prognostic value of epidermal growth factor receptors, determined by both immunohistochemistry and ligand binding assays, in primary epithelial ovarian cancer: a pilot study.

After our previous studies on the incidence of epidermal growth factor receptors (EGF-R) and its relationships with other tumour characteristics in more than 100 ovarian tumours, in the present study we investigated the prognostic value of EGF-R with respect to progression-free survival in 50 patients with primary ovarian cancer and sufficient follow-up (median 26 months, range 10-33 months). EGF-R was measured by both biochemical and two immunohistochemical methods, using two monoclonal antibodies (MAb), in addition to oestrogen receptors (ER) and progesterone receptors (PgR). EGF-R by ligand binding assay and Scatchard analysis were detectable in 63% of the tumours, by immunohistochemistry with MAb 2E9 in 82% and with MAb EGF-R1 in 78% of the tumours. ER-positivity was found in 58% and PgR-positivity in 38% of the patients. The results of the three measurements of EGF-R showed only weak to moderate associations with Spearman rank correlations (Rs) between 0.13 and 0.46. ER and PgR were only weakly correlated (Rs = 0.20) and they showed no significant association with EGF-R status. There was no clear evidence of the existence of correlations between receptor values and FIGO stage and tumour rest. Univariate Cox regression analyses showed that a higher FIGO stage and larger tumour rest were associated with shorter progression-free survival (P = 0.001), while PgR positivity was associated with a longer progression-free survival (P = 0.02). The level of EGF-R (irrespective of the method of determination used) showed a positive correlation with the risk of progression, but this correlation was not statistically significant.

Adult↗
PubMed1992

Receptors for hormones and growth factors and (onco)-gene amplification in human ovarian cancer.

Receptor status and gene amplification were studied in advanced human ovarian adenocarcinoma tissues, borderline and benign ovarian tumours and normal ovarian tissues. Sixty-five percent (53/82) of ovarian adenocarcinomas, 57% (8/14) of benign/borderline tumours and only 31% (5/16) of normal ovarian tissues studied showed specific 125I-EGF (epidermal growth factor) binding (median: 17; 10; and 0 fmol EGF-R/mg protein, respectively) and a significant increase in progesterone receptor (PgR) levels was observed in these groups (median: 5; 33; and 152 fmol/mg protein, respectively). No correlations were observed between the levels of EGF-R and the levels of either oestrogen receptors (ER) or PgR. All membrane samples of 25 adenocarcinomas studied by Scatchard analysis were positive for insulin-like growth-factor-I receptors (IGF-I-R) and contained higher IGF-I-R levels than membranes of 10 normal ovarian tissues, of which 9 were positive (median: 64 and 26 fmol IGF-I-R/mg membrane protein, respectively). Also, as measured by autoradiography, 37 adenocarcinoma tissues showed a higher expression of IGF-I-R (1.5+ to 4+) than sections derived from 10 normal ovarian tissues (1+). 125I-IGF-I binding was predominantly associated with epithelial tumour cells, the surrounding connective tissue was negative and in several samples high expression of IGF-I-R was found in areas of tumour necrosis. Southern blot analysis of DNAs isolated from 25 ovarian adenocarcinomas revealed no amplification of the IGF-I-R or the EGF-R gene. The HER2/neu gene was amplified only in 2 out of 3 histologically confirmed endometrioid adenocarcinomas studied but not in 22 other tumours. An amplification of the c-myc gene was observed in 28% (7/25) of the tumours. All c-myc-amplified tumours were PgR-negative. No rearrangement was observed for any of the genes studied. In conclusion, ovarian adenocarcinoma tissues show a decrease in PgR levels and an increased expression of IGF-I-R and EGF-R, in the absence of gene amplification, when compared to benign/borderline ovarian tumours and normal ovarian tissues. In addition, amplification of the c-myc and HER2/neu genes, without rearrangement of these genes, occurs in a minority of these tumours.

Adenocarcinoma↗
PubMed1992

Occurrence of epidermal growth factor receptors in benign and malignant ovarian tumors and normal ovarian tissues: an immunohistochemical study.

Epidermal growth factor receptor (EGF-R) was studied with monoclonal antibody 2E9 on 50 ovarian tumors of various histological types and 10 non-tumorous ovarian tissues by immunohistochemistry. Enhanced expression was observed in 26/50 (52%) of the tumors. Only 25 out of 46 epithelial tumors (54%) showed positivity in epithelial tumor cells. Staining was cytoplasmic in all cases. No correlation was established between EGF-R expression and the histological type of the epithelial tumor. Apart from EGF-R expression in tumor cells, low immunoreactivity was also observed in stromal and endothelial cells in both normal and tumorous ovarian tissues. Furthermore in 8/9 specimens containing necrotic areas, EGF-R was noticed in these areas as well. Both of the latter observations may have impact on the evaluation of the prognostic value of EGF-R activity in tumors, when based on EGF-R measurements using biochemical binding studies. We therefore recommend that EGF-R is measured with both methods in studies regarding its clinical value.

Adenocarcinoma↗
PubMed1992

Weekly low-dose mitoxantrone plus doxorubicin as second-line chemotherapy for advanced breast cancer.

Weekly low dose mitoxantrone (3 mg/m2) plus doxorubicin (8 mg/m2) was administered as second-line chemotherapy to 33 patients with advanced breast cancer. Four out of 28 evaluable patients (14%) obtained a partial response with a median duration of 34 weeks (range 18-67+ weeks), while 8 patients (29%) showed stable disease with a median duration of 28 weeks (range 11+-60 weeks). Gastrointestinal toxicity and alopecia were mild. Grade II and III leukopenia occurred in 63% of the courses without serious infectious disease. Four patients experienced an asymptomatic drop of 16-20% in the left ventricular ejection fraction (LVEF) after relatively low cumulative doses of each drug, and one patient with a history of pericarditis carcinomatosa and mediastinal irradiation developed a heart failure. In conclusion, this second-line combination treatment had moderate activity in breast cancer and caused only few subjective side effects, especially with respect to gastrointestinal symptoms.

Adult↗
PubMed1991

Randomised phase II trial of carboplatin and iproplatin in advanced urothelial cancer.

47 patients with advanced urothelial cancer and no prior chemotherapy were randomly assigned to therapy with either carboplatin or iproplatin. Both platinum analogues were administered intravenously every 28 days at doses of 400 mg/m2 carboplatin and 300 mg/m2 iproplatin. None of 14 evaluable patients treated with carboplatin responded. Therefore, this arm was closed and from then on all eligible patients were registered on the iproplatin arm. 5 of 29 evaluable patients treated with iproplatin achieved a partial response (17%) for a median duration of 27 weeks (range 22-37). Iproplatin did not induce renal function disturbance. Gastrointestinal toxicity was mild to moderate. Bone marrow toxicity predominantly consisted of thrombocytopenia and required platelet transfusions in 13% of patients. 2 patients developed hypersensitivity reactions. It is concluded that the bone marrow toxicity and the chance of hypersensitivity render iproplatin an unattractive alternative to cisplatin.

Adult↗
PubMed1991

Carboplatin and cyclophosphamide salvage therapy for ovarian cancer patients relapsing after cisplatin combination chemotherapy.

30 ovarian cancer patients with a relapse after prior cisplatin combination chemotherapy were treated in a phase II study with cyclophosphamide 100 mg/m2 orally on days 1-7 and carboplatin 300 mg/m2 intravenously on day 8. Treatment was well tolerated. The major side-effect was thrombocytopenia. 28 patients were evaluable for response. The response was 5 CRs (18%), 4 PRs (14%) 15 SDs (53%) and 4 PDs (14%), for an overall response rate of 32%. The overall progression-free survival lasted from 2 to 23 months, median 8 months. Overall survival ranged from 2 to 35+ months, median 12 months. Patients with a therapy-free interval of more than 1 year showed a higher response rate (46%) than patients with a shorter therapy-free interval (20%). It is concluded that platinum containing second-line chemotherapy, after treatment that already contained cisplatin, is only warranted to palliate symptoms.

Adult↗
PubMed1991

BOP/VIP--a new platinum-intensive chemotherapy regimen for poor prognosis germ cell tumours.

Ninety-one patients with poor prognosis non-seminomatous germ cell tumours (NSGCT) were treated with an initial intensive chemotherapy schedule. Suitable patients fulfilled one or more of the following criteria: lymph node metastases greater than 10 cm diameter; liver, brain or bone metastases; serum HCG level greater than 50,000 IU/L; and extragonadal primary tumours. Treatment consisted of 3 cycles of bleomycin, vincristine and cisplatin (BOP) administered at 10 day intervals, followed by 3 cycles of etoposide, ifosfamide and cisplatin (VIP) at 21 day intervals. A total of 64 patients (70%) achieved a complete remission. This comprised 46 patients who received BOP/VIP only, and 18 patients who received additional chemotherapy after BOP/VIP. Of these 64 patients, 51 underwent complete surgical resection of residual masses, including 11 in whom there was evidence of teratoma with cellular atypia or non-germ cell cancer in the resected tissue. A further 9 patients had persisting unresected radiological masses in the presence of marker complete remission. The overall response rate was 80%. Currently 57 patients (63%) remain alive and free from disease progression. The median follow-up period is 90 weeks (range 24-206 weeks), with a 2 yr actuarial progression-free survival of 66% (95% c.i. 55-77%). Major toxicity was myelosuppression, occurring during the VIP arm of therapy, with a median nadir WBC of 1.1 x 10(9)/L and median platelet count of 51 x 10(9)/L. Other toxicity included peripheral neuropathy (WHO Grade 2 and 3 in 22%). We conclude that treatment results with the BOP/VIP schedule in this poor prognosis patient group are at least comparable with other schedules, and toxicity is manageable.(ABSTRACT TRUNCATED AT 250 WORDS)

Antineoplastic Combined Chemotherapy Protocols↗