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Biomedical subjects

J B Vermorken

Publications and source records attributed to J B Vermorken.

At least 19 recordsLinked to original sources
PubMed2006

Phase II study of bleomycin, vindesine, mitomycin C and cisplatin (BEMP) in recurrent or disseminated squamous cell carcinoma of the uterine cervix.

OBJECTIVE: We carried out a phase II trial with BEMP [bleomycin, vindesine (Eldisine(R)), mitomycin C and cisplatin] in patients with recurrent and/or metastatic squamous cell carcinoma of the uterine cervix with the specific aim to assess whether BEMP was of particular interest when certain disease sites were involved. PATIENTS AND METHODS: Eligible patients received four cycles of E 3 mg/m(2), day 1 + 8; P 50 mg/m(2), day 1; B 15 mg/day (continuous infusion), day 2-4 and M 8 mg/m(2), day 5 (on alternate cycles), every 3 weeks during an induction phase. Thereafter, those without progression continued with MEP every 4 weeks in a maintenance phase. MEP consisted of E 3 mg/m(2), day 1 + 8, M 6 mg/m(2) (on alternate cycles) and P 50 mg/m(2), both on day 1. All drugs were given i.v. Both response evaluation and toxicity grading were assessed according to World Health Organization criteria. RESULTS: Of the 161 eligible patients, 143 were assessable for survival, 148 for toxicity and 131 for response. Overall response rate was 45% [complete (CR) 14.5%, partial response (PR) 30.5%]. Most responsive disease sites were lung, lymph nodes and skin metastases (>60% response, CR rate >25%). Median duration of response was 7.6 months. Survival was significantly better in patients with only distant metastases: 12.9 months versus 8.6 months in those with other disease sites involved (P = 0.002). In a multivariate analysis, patients with a good performance status yielded a better prognosis (P = 0.0017), as did the patients with only metastatic disease compared with those who had pelvic disease also or solely (P = 0.045). There were two toxic deaths and 21% of patients stopped treatment because of excessive toxicity. CONCLUSIONS: Patients with a good performance status and only distant metastases seem optimal candidates to receive the BEMP regimen. This benefit should be balanced against the expected serious toxic effects.

Adult↗
PubMed2006

Bisphosphonates and osteonecrosis of the jaw: cause and effect or a post hoc fallacy?

BACKGROUND: An increasing amount of reports are being published suggesting a relationship between the use of bisphosphonates (BPs) and the development of osteonecrosis of the jaw (ONJ). We reviewed the currently available evidence and explore the potential mechanisms of action based on the known effects of the concerned BP. DESIGN: The MEDLine, Current Contents and Science Citation Index Expanded databases were queried and the results augmented by analyzing cited references and recent congress proceedings. RESULTS: 22 papers were included detailing 225 patients, all based on retrospective chart review without control groups. The prevalence of ONJ was estimated at 1.5%. The involved BPs were pamidronate, zoledronic acid, alendronate and risedronate, all potent nitrogen-containing agents. The most common symptom was pain (81.7%), although 12.2% of cases were asymptomatic. In 69.3% of patients ONJ was preceded by a dental extraction. At the time of diagnosis, 74.5% of patients were receiving chemotherapy and in 38.2% of cases corticosteroids were administered. Although various conservative and surgical treatment modalities were reported, residual sites of ONJ persisted in 72.5% of cases. CONCLUSION: Although not enough evidence is available to prove a causal link, it seems that under specific circumstances local defenses can become overwhelmed resulting in ONJ.

Bone Density Conservation Agents↗
PubMed2005

A study from the EORTC new drug development group: open label phase II study of sabarubicin (MEN-10755) in patients with progressive hormone refractory prostate cancer.

Sabarubicin (MEN-10755), a new synthetic anthracycline analogue, was evaluated for safety and efficacy in a multicentre phase II study in patients with advanced hormone refractory prostate cancer (HRPC). Thirty seven patients were included, of which 34 were evaluable for PSA response according to Bubley's criteria. Sabarubicin was administered as a short (30 min) intravenous infusion at a dose of 80 mg/m(2) every 3 weeks. The main toxicity consisted of grade 3/4 neutropenia in 24 patients (64.9%), with grade 3/4 febrile neutropenia occurring in one patient only. Grade 3/4 cardiotoxicity was observed in 4 patients including one ineligible. Other toxicities were mild. Nine patients achieved a PSA response (26.5%), 10 patients had stable disease (29.4%) and 14 patients disease progression (41.2%). One patient (2.9%) had a PSA response that was not confirmed by repeat PSA testing. The objective response rate according to RECIST criteria was 6.7% in 15 patients with measurable disease. The median duration of PSA responses was relatively long 7.1 months (95% CI 4.9-20.7) as was the median time to treatment progression in patients with stable disease. The median overall survival was 18.7 months (95% CI 9.1-N), comparable to results recently observed in taxotere-containing regimens. To confirm and extend these results, further testing of sabarubicin in larger trials is warranted.

Aged↗
PubMed2005

Immunotherapy with autologous tumor cell-BCG vaccine in patients with colon cancer: a prospective study of medical and economic benefits.

We have completed a multicenter, randomized controlled phase III clinical trial in Stages II and III colon cancer patients with active specific immunotherapy (ASI) using autologous tumor cells with an immunomodulating adjuvant bacillus Callmette-Guerin (BCG) vaccine (OncoVAX) in an adjuvant setting. In this study, patients were randomized to receive either OncoVAX therapy or no therapy after surgical resection of the primary tumor and stratified by stage of disease. Since the biologic essence of the effective tumor immunotherapy is the presence in the vaccine of a minimum number of viable, metabolically active, autologous tumor cells, the processing of the vaccine product, occurred within 48 h after surgery. Analysis of prognostic benefit in the pivotal phase III trial, with a 5.8 year median follow-up, showed that a beneficial effect of OncoVAX is statistically significant for all endpoints including recurrence-free interval, overall survival, and recurrence-free survival in Stage II colon cancer patients. Surgery alone cures approximately 65% of Stage II (Dukes B2, B3) colon cancer patients. In the remaining patients, OncoVAX in an adjuvant setting, significantly prolongs recurrence-free interval (57.1% relative risk reduction) and significantly improves 5-year overall survival and recurrence-free survival. No statistically significant prognostic benefits were achieved in Stage III (Duke's C1-C3) patients. A health economics assessment was performed on these results in Stage II colon cancer patients using disease-free survival and overall survival (for the entire intent-to-treat population). Cost-effectiveness, cost-utility and sensitivity analysis were applied with, cost of life years, recurrence-free life years and quality adjusted life years (QALYs) as the primary endpoints to this analysis. The perspective of the economic analysis was the current direct medical cost established by the health care providers. The introduction of new technologies often leads to additional costs. This report verified that the use of OncoVAX for patients with Stage II colon cancer not only has significant prognostic benefit and positive clinical outcomes, but also showed that OncoVAX therapy yields impressive health economics benefits.

Adult↗
PubMed2005

Multicentre EORTC study 16997: feasibility and phase II trial of farnesyl transferase inhibitor & gemcitabine combination in salvage treatment of advanced urothelial tract cancers.

In this study, the feasibility and activity of combined chemotherapy of the farnesyl transferase inhibitor SCH66336 and gemcitabine was evaluated. This therapy was used as second-line treatment in patients with advanced urothelial tract cancer and the influence of SCH66336 exposure on the pharmacokinetics of gemcitabine was also determined. Patients who had received one previous chemotherapy regime for advanced urothelial cancer were treated with a combination of SCH66336 (150 mg in the morning and 100 mg in the evening) and Gemcitabine (1000 mg/m2 on day 1, 8 and 15 per 28-day cycle). Dosages of gemcitabine and its metabolite dFdU were performed on day one of cycle 1 before exposure to SCH66336 and day one of cycle 2. A total of 152 cycles were administered in 33 patients (median 3, range: 1-15). No patients had severe hematological toxicity, defined as Grade 4 thrombocytopenia or febrile neutropenia. Nine partial responses and one complete response were achieved in 31 assessable patients and corresponded to an overall response rate of 32.3% [95% CI:17%-51%]. There was no influence of exposure to SCH66336 on the level of gemcitabine or dFdU in 11 assessable patients. In conclusion, a combination of SCH66336 and gemcitabine is feasible in terms of toxicity and active as second-line treatment in patients with advanced urothelial tract cancer. SCH66336 had no effect on the pharmacokinetics of gemcitabine. Randomised trials should be undertaken to clarify the role of SCH66336 in combination with gemcitabine in cancer treatment.

Adult↗
PubMed2005

Bendamustine prolongs progression-free survival in metastatic breast cancer (MBC): a phase III prospective, randomized, multicenter trial of bendamustine hydrochloride, methotrexate and 5-fluorouracil (BMF) versus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first-line treatment of MBC.

Two i.v. regimens, bendamustine, methotrexate and 5-fluorouracil (BMF) and cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were compared as first-line therapy in a randomized, open, multicenter phase III trial including 364 patients with metastatic breast cancer (MBC). Bendamustine is an anti-neoplastic agent with alkylating, but also additional, so far unclear, mechanisms of action. We wanted to show the superiority of BMF over CMF in terms of time to progression (TTP) (primary endpoint), overall response, response duration, toxicity and quality of life (QoL). TTP was significantly longer in the BMF group (8.2 versus 6.7 months for CMF) (p=0.0071). The effect of BMF on TTP was more pronounced in the stratum 'prior adjuvant therapy, no visceral metastases' (p=0.034). Overall response rates and QoL did not significantly differ between the regimens. BMF caused more mucositis and leukopenias. Thus, bendamustine, when replacing cyclophosphamide in the CMF combination, can be expected to produce longer progression-free survival in first-line treatment of MBC.

Adolescent↗
PubMed2004

Phase II study of OSI-211 (liposomal lurtotecan) in patients with metastatic or loco-regional recurrent squamous cell carcinoma of the head and neck. An EORTC New Drug Development Group study.

The purpose of this study was to evaluate the activity and safety of OSI-211, the liposomal form of lurtotecan, in patients ineligible for curative surgery or radiotherapy and with metastatic/locoregional recurrent squamous cell carcinoma of the head and neck (SCCHN) and target lesions either within a previously irradiated field ("within") or outside a previously irradiated field ("outside"). OSI-211 was given intravenously over 30 min on days 1 and 8 at 2.4 mg/m2/day, repeated every 21 days (1 cycle). From July 2001 to March 2002, 32 patients from 14 institutions were enrolled in the "within" arm and 18 in the "outside" arm. In the "within" arm, two patients were ineligible because their tumour site was not allowed in the protocol (nasopharynx, skin) and two other patients never started treatment. Of the 46 eligible patients who started treatment, there was one objective response (response rate: 2.2% (95% Confidence Interval (CI): [0-11.5%]). Twelve patients in the "within" arm and 6 in the "outside" arm had stable disease, with a median duration of 18 weeks, 95% CI (12.7-25.7). The median time to progression was 6 weeks (95%CI: [5.9-12.7] weeks). Haematological toxicity was moderate in both arms. The most common haematological toxicity was grade 1-2 anaemia in 79% of patients. Non-haematological toxicity was mild in both arms. The most common grade 3-4 non-haematological toxicity was infection in 8.5% of patients. OSI-211 administered on d1 and d8, every 3 weeks, is well tolerated, but shows only minimal activity in locally advanced/metastatic SCCHN.

Adult↗
PubMed2004

Risk factors for cervical cancer development: what do women think?

BACKGROUND: The current cervical cancer prevention strategy is exclusively directed towards screening, without taking into account any relationship with sexual risk factors. The introduction of human papillomavirus (HPV) detection into the screening procedure implicates that we should give attention to this relationship. The aim of this study was to investigate what knowledge women have of the relation between HPV and cervical cancer. METHODS: Rather than asking about HPV specifically, we suggested 20 risk factors for the development of cervical cancer, including viral infection, and asked 73 women visiting their general practitioner, 67 women visiting a lecture on risk factors for cervical cancer and 28 female students in biomedical sciences to rate the importance of these risk factors on a scale of 1-5. RESULTS: Genetic factors were rated highest with a mean score of 4.5. Bacterial infection ranked second highest with a mean score of 3.8. Smoking ranked fourth at a mean score of 3.6, whereas viral infection shared the sixth place with number of sexual partners with a mean score of 3.4. The presence of high voltage power lines and physical activity appropriately scored the last two places at 2.4 and 2.2, respectively. Twenty-one women suggested a role for sexually transmitted agents, but only five women (3.1%) could actually pinpoint HPV. CONCLUSION: This enquiry indicates that the risk factor 'genetic factors' was over-rated, while knowledge of the most important risk factors, i.e. smoking and sexual habits and (sexually transmitted) infections, would appear to be present to a moderate level in our population. However, knowledge of the role of HPV in cervical cancer development is lacking.

Adult↗
PubMed2004

Is there still a role for neoadjuvant chemotherapy in head and neck cancer?

After approximately 20 years of conflicting results from chemotherapy in randomized trials in advanced head and neck cancer, three meta-analyses reviewed its use. All three concluded that chemotherapy was associated with a statistically significant advantage in survival, but that this was low (4% absolute benefit at 2 and 5 years). The improvement in survival was mainly based on the more robust improvement obtained with the concomitant use of chemotherapy and radiotherapy. Induction chemotherapy, in particular, was not associated with any relevant survival advantage. This article reviews current indications for neoadjuvant chemotherapy in advanced head and neck cancer. Implications for current and future research are discussed.

Biomarkers↗
PubMed2004

Docetaxel, cisplatin and 5-fluorouracil in patients with locally advanced unresectable head and neck cancer: a phase I-II feasibility study.

PURPOSE: To determine the safety profile and activity of the combination of docetaxel, cisplatin and 5-fluorouracil (5-FU) in chemotherapy-naive patients with squamous cell carcinoma of the head and neck (SCCHN). PATIENTS AND METHODS: Patients with locally advanced unresectable SCCHN were treated with docetaxel and cisplatin both as a 1-h infusion on day 1 followed by a continuous infusion of 5-FU for 5 days. Cycles were planned every 3 weeks up to four cycles, whereafter the patients were treated with locoregional radiotherapy. Two dose levels were studied. Doses in level I were 75 mg/m(2) of docetaxel, 75 mg/m(2) of cisplatin and 750 mg/m(2)/day of 5-FU; in level II the cisplatin dose was escalated to 100 mg/m(2). Following chemotherapy, all patients were to receive curative radiotherapy according to the standards in the different institutions. RESULTS: Twenty-five patients were treated at dose level I with 86 cycles (median four; range one to four), and 23 at dose level II with 84 cycles (median four; range two to four). The median relative dose intensity was 0.99 (range 0.86-1.04) at level I and 0.94 (range 0.79-1.02) at level II. The response rate in the intention-to-treat population was 64% [95% confidence interval (CI) 42.5% to 82%] in level I and 78.3% (95% CI 56.3% to 92.5%) in level II; all were partial responses. The maximum tolerated dose was reached at level II with renal toxicity, nausea, stomatitis and thrombocytopenia as principal dose-limiting toxicities. The median survival of the 48 patients was 18.5 months. The survival at 12, 18, 24 and 30 months was 69, 54, 41 and 31%, respectively. CONCLUSIONS: The combination of docetaxel, cisplatin and 5-FU associated with prophylactic ciprofloxacin is feasible and active in patients with SCCHN. Dose level I is recommended for phase III testing.

Adult↗
PubMed2004

A multicentre, randomised phase II study of weekly or 3-weekly docetaxel in patients with metastatic breast cancer.

BACKGROUND: A phase II randomised trial was conducted to evaluate the tolerability and activity of weekly or 3-weekly docetaxel in patients with metastatic breast cancer. PATIENTS AND METHODS: Eighty-three patients with histologically proven metastatic breast cancer were randomised to receive either docetaxel 40 mg/m2 weekly for 6 consecutive weeks followed by 2 weeks without treatment (n = 41), or docetaxel 100 mg/m2 on day 1 every 3 weeks (n = 42). RESULTS: The incidence of all grade 3-4 adverse events was higher in the 3-weekly group than in the weekly group (96 versus 44), and the number of patients with grade 3-4 adverse events was also greater in the 3-weekly group (31 versus 20). Analysis of individual adverse events tended to favour the weekly regimen. Intent-to-treat overall response rate was 34% and 33% in the weekly and 3-weekly groups, respectively. Median time to progression was 5.7 and 5.3 months after weekly and 3-weekly docetaxel, respectively, and median time to treatment failure was 4.1 and 4.9 months, respectively. CONCLUSION: Weekly docetaxel is an active regimen in metastatic breast cancer with comparable efficacy to 3 weekly docetaxel. Although both schedules were well tolerated, weekly docetaxel appears to have a more favourable toxicity profile.

Adult↗