Publications by authors named "Marika Rasschaert"

15 Publications

  • Page 1 of 1

EVALUATION OF A SUPERVISED PHYSICAL ACTIVITY PROGRAMME FOR CANCER SURVIVORS: FROM TREATMENT TO TRIATHLON.

J Rehabil Med Clin Commun 2020 31;3:1000030. Epub 2020 Mar 31.

Multidisciplinary Oncological Center of Antwerp (MOCA), Antwerp, Belgium.

Objective: It is recommended that cancer survivors incorporate physical activity into their daily lives after in-hospital rehabilitation. However, there is a lack of training programmes focusing on the specific needs of cancer survivors. TriaGO! - an 8-month intervention study of aerobic endurance training for cancer survivors - was therefore examined. The training programme aims to meet the participants' physical needs and provide socio-emotional support, in the form of an exercise programme that challenges participants to aim to compete in an Olympic- distance triathlon (1,000 m swimming, 45 km cycling, 10 km running) after 8 months' of training.

Methods: The TriaGO! training programme was provided to in-hospital rehabilitated cancer survivors ( = 12). Each patient invited a healthy friend or family member to train with them (a so called buddy ( = 12)). The 8-month programme involves supervised training sessions, combining cycling, swimming and running, which progress in frequency, duration and intensity. Physical health was measured at the start, 4 and 8 months, using objective parameters of aerobic fitness, muscular fitness and body composition.

Results: A total of 22 out of 24 participants successfully completed the training programme and the triathlon. Both the cancer survivors and their buddies showed significant improvements in physical health. Cancer survivors showed improvements in aerobic fitness, as increases in VOmax and VOpeak of 5.5 ml.kg.min and 0.26 ml.min respectively ( <0.0001). Buddies underwent similar significant increases; 5.39 ml.kg.min and 0.18 ml.min, respectively.

Conclusion: The TriaGO! training programme introduces the concept of supervised endurance training for cancer survivors. Through measurement of ob-jective parameters, this study demonstrated that significant physical reconditioning is possible in cancer survivors. A supervised programme would be recommended for all cancer patients after in-hospital treatment, in order to facilitate the transition to incorporation of physical activity into daily life.
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http://dx.doi.org/10.2340/20030711-1000030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8008719PMC
March 2020

The tele-transition of toxicity management in routine oncology care during the severe acute respiratory syndrome (SARS-CoV-2) pandemic.

Br J Cancer 2021 04 9;124(8):1366-1372. Epub 2021 Feb 9.

Department of Oncology, Antwerp University Hospital Antwerp, Antwerp, Belgium.

Background: Telehealth modalities were introduced during the SARS-CoV-2 pandemic to assure continuation of cancer care and maintain social distance.

Methods: This is a retrospective cohort analysis of our telehealth expansion programme. We adapted two existing patient-reported outcome (PRO) telemonitoring tools that register and (self-)manage toxicities to therapy, while screening for SARS-CoV-2-related symptoms. Outpatients from a tertiary cancer centre were enrolled. The adapted PRO interface allowed for uniform registration of SARS-CoV-2-related symptoms and effective triage of patients at home where we also implemented systematic throat washings, when available.

Results: Three hundred and sixty patients registered to the telemonitoring systems from March 13 to May 15, 2020. Four prespecified SARS-CoV-2 alarms resulted in three patients with positive PCR testing. Other Covid-19 symptoms (fever 5× and cough 2×) led to pretreatment triage resulting in 1 seroconversion after initial negative testing. One of the 477 throat washings proved positive.

Conclusions: The rapid adoption of an amended PRO (self-)registrations and toxicity management system was feasible and coordinated screening for Covid-19. Continued clinical cancer care was maintained, with significant decreased waiting time. The systemic screening with throat washings offered no real improvement.
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http://dx.doi.org/10.1038/s41416-020-01235-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039036PMC
April 2021

Prescreening for COVID-19 in patients receiving cancer treatment using a patient-reported outcome platform.

ESMO Open 2020 06;5(3):e000817

Department of Medical Oncology, MOCA, University Hospital Antwerp (UZA), Antwerp, Belgium; Department of Molecular Imaging, Pathology, Radiotherapy & Oncology (MIPRO), Center for Oncological Research (CORE), Antwerp University, Antwerp, Belgium.

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http://dx.doi.org/10.1136/esmoopen-2020-000817DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307523PMC
June 2020

AMTRA: a multicentered experience of a web-based monitoring and tailored toxicity management system for cancer patients.

Support Care Cancer 2021 Feb 9;29(2):859-867. Epub 2020 Jun 9.

Department of Oncology, Multidisciplinary Oncological Center Antwerp, MOCA, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.

Background: Technology-based interventions are increasingly being introduced in routine clinical cancer care. There is a need for reliable systems to monitor treatment-related toxicity in a standardized manner. Such electronic tools bridge the gap in providing quality home-based monitoring.

Methods: From July 2017 to December 2017, we performed a multicentered, non-randomized prospective cohort analysis with patients who were receiving routine chemotherapy for various solid tumors, using a web-based patient-reported toxicity registration, management, and intervention system called AMTRA (ambulatory Monitoring of cancer Therapy using an interactive Application) linked to the homecare nursing organization Remedus®. Twelve common toxicities plus pain and two biometrics could be registered daily or more frequently as required. These were processed centrally to generate tailored advice for lesser symptoms or a phone call from a dedicated nurse in case of severe or prolonged toxicity. A compliance tool to monitor oral therapies was incorporated in the system.

Results: One hundred sixty-eight patients (92%) were enrolled, with 31,514 registrations analyzed. One hundred eight patients reported severe toxicity (> 1461 registrations), resulting in 102 clinical interventions ranging from self-management advice, supplemental consultations to hospitalizations. Compliance to oral chemotherapy was high using AMTRA with a median of 98.7% (95 confidence interval (CI) [93.5-100.0%]). Seventy-nine percent of patients stated that the availability of AMTRA self-reports was useful in communication with the care provider, while 75% felt more in control while managing their treatment.

Conclusions: The application of an interactive PRO-system in routine symptom management of cancer patients allowed standardized documentation of toxicities and recorded a high compliance with oral treatment. It allows for rapid interaction for toxicities and cancer-related symptoms experienced at home.
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http://dx.doi.org/10.1007/s00520-020-05550-6DOI Listing
February 2021

The predictive value of primary tumor location in patients with metastatic colorectal cancer: A systematic review.

Crit Rev Oncol Hematol 2018 Jan 7;121:1-10. Epub 2017 Nov 7.

Center of Oncological Research (CORE), University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium; Center of Medical Genetics, University of Antwerp and Antwerp University Hospital, Prins Boudewijnlaan 43/6, 2650 Edegem, Belgium. Electronic address:

Colorectal cancer (CRC) is one of the most frequently diagnosed cancers worldwide. It has been reported that left- and right-sided CRC harbor varying disease characteristics, which leads to a difference in prognosis and response to therapy. Recently, there have been retrospective studies about tumor location in metastatic CRC (mCRC) and its potential to predict the effect of anti-vascular endothelial growth factor and anti-epidermal growth factor receptor (anti-EGFR) therapies. In this review, we provide a comprehensive overview of the latest trials studying the predictive value of primary tumor location in mCRC and discuss biomarkers that might be associated with the differences in treatment response. Although data need to be interpreted with caution due to the absence of randomized trials stratified based on tumor location, patients with left-sided CRC seem to benefit more from anti-EGFR therapy than patients with right-sided CRC. Further clinical trials, stratified for tumor location, are warranted.
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http://dx.doi.org/10.1016/j.critrevonc.2017.11.003DOI Listing
January 2018

Which Factors Predict Overall Survival in Patients With Metastatic Castration-Resistant Prostate Cancer Treated With Abiraterone Acetate Post-Docetaxel?

Clin Genitourin Cancer 2017 08 1;15(4):502-508. Epub 2017 Feb 1.

Department of Urology, Ghent University Hospital, Ghent, Belgium.

Background: Abiraterone acetate (AA) increases overall survival (OS) in patients with metastatic castration-resistant prostate cancer (mCRPC) previously treated with docetaxel. However, survival time varies substantially between individuals. Our goal was to identify prognostic factors that better estimate OS.

Materials And Methods: This is a retrospective multicentric analysis of 368 patients with mCRPC starting AA with prednisone after docetaxel. Cox proportional hazards statistics were applied. A multivariate model was constructed based on significant univariate predictors by using a manual stepwise forward and backward selection strategy. Model performance was determined by using receiver operating characteristic (ROC) curves.

Results: Univariate analysis identified 20 significant OS predictors. A multivariate model was constructed, based on 220 patients, incorporating 5 independent risk factors for decreased OS at the time of AA initiation: hemoglobin < 12 g/dL (hazard ratio [HR] 2.02), > 10 metastases (HR 1.80), ECOG performance status ≥ 2 (HR 1.88), radiographic progression (HR 1.50), and time since diagnosis < 90 months (HR 1.66, all P < .05). Patients were stratified into 3 groups: good (0-2 risk factors, median OS 22.6 months), intermediate (3 risk factors, median OS 13.9 months), and poor prognosis (4-5 risk factors, median OS 6.2 months). The area under the ROC curve based on the event "death by the time of median OS (13.3 months)" was 0.736 (95% confidence interval 0.670-0.803).

Conclusion: We identified 5 readily available risk factors independently associated with decreased OS. The resulting model may be used for patient counseling in daily clinical practice, as well as patient stratification in clinical trials.
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http://dx.doi.org/10.1016/j.clgc.2017.01.019DOI Listing
August 2017

Innovative molecular targeted agents in hepatocellular carcinoma: new gladiators on the arena.

Minerva Chir 2017 Jun 14;72(3):206-218. Epub 2017 Feb 14.

Phase I, Early Clinical Trials Unit, Antwerp University Hospital and Center for Oncological Research (CORE), Antwerp University, Antwerp, Belgium -

Treatment of advanced hepatocellular carcinoma remains a challenge, with discouraging results in terms of survival. Following the approval of the multikinase inhibitor sorafenib, a large number of molecular targeted agents have been tested, but many have failed to demonstrate significant efficacy in clinical trials. However, the deeper knowledge in HCC pathogenesis achieved through the years has enabled us to explore new targetable pathways as well as biomarkers that could lead to treatment personalization. In this review, we provide a comprehensive update of the most recent data regarding new drugs under investigation ‒ some like regorafenib, very close to its approval ‒ and new possible targets for future treatments.
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http://dx.doi.org/10.23736/S0026-4733.17.07311-4DOI Listing
June 2017

Corrigendum to "Implementation of geriatric assessment-based recommendations in older patients with cancer: A multicenter prospective study" [J. Geriatr. Oncol. 6 (2015) 401-410].

J Geriatr Oncol 2016 Mar 8;7(2):142-3. Epub 2016 Feb 8.

Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium. Electronic address:

The authors regret: A calculation error was corrected in Table 3. As mentioned under the table, the percentage of patients under ‘Baseline’ was calculated from the total no. of patients with geriatric recommendations data (n = 932 pts). This was mistakenly calculated from the number of patients with available GA data (n = 979). Percentages have been recalculated. The corrected table is reproduced here (Table 3). We emphasize that these percentages are not mentioned in the text of the paper nor do they change any of the conclusions. The authors would like to apologize for any inconvenience caused.
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http://dx.doi.org/10.1016/j.jgo.2016.01.005DOI Listing
March 2016

Feasibility of an interactive electronic self-report tool for oral cancer therapy in an outpatient setting.

Support Care Cancer 2016 08 30;24(8):3567-71. Epub 2016 Mar 30.

Department of Oncology, Multidisciplinary Oncological Center Antwerp, MOCA, University Hospital Antwerp, Wilrijkstraat 10, 2650, Edegem, Belgium.

Background: The introduction of oral anti-cancer agents provides a convenient administration route for chronic cancer treatment to outpatients. Health information technology through web-based applications or other electronic tools can offer a platform to improve treatment compliance, symptom management, and patient-provider communication.

Purpose: The purposes of this study were to test the feasibility and clinical utility of an electronic self-report device (RemeCoach) for patients or their caregivers and to register and prospectively evaluate the quality of data generated.

Patients And Methods: Patients using Teysuno® (S-1) for advanced gastrointestinal carcinoma used a pre-programmed device in order to register compliance to treatment and six clinical parameters. Real-time data were collected onto a central platform, which processed the data by an algorithm. This algorithm stratified the data into different grades based on the Common Terminology Criteria for Adverse Events (CTCAE v4.0).

Results: From December 2013 to March 2014, 11 patients (5 men, 6 women) were enrolled. Compliance to the device was high, six patients (55 %) registered timely intake of medication (demonstrating >95 % treatment compliance). Agreement between patients' and clinicians' reported toxicity was substantial for nausea, but discrepant for fatigue, hand-foot syndrome, and mucositis.

Conclusion: The use of an interactive self-report tool is feasible, reliable, and acceptable to outpatients. The RemeCoach and the algorithm devised will be further developed as an interactive patient-reported outcome (PRO) system, to improve early detection of side effects in an outpatient setting. Further studies are needed to confirm these data and to explore the relationship between optimal patient support and efficacy of treatment.
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http://dx.doi.org/10.1007/s00520-016-3186-2DOI Listing
August 2016

Abiraterone acetate post-docetaxel for metastatic castration-resistant prostate cancer in the Belgian compassionate use program.

Urol Oncol 2016 06 2;34(6):254.e7-254.e13. Epub 2016 Feb 2.

Department of Urology, Ghent University Hospital, Ghent, Belgium.

Background: Abiraterone acetate (AA) is licensed for treating metastatic castration-resistant prostate cancer (mCRPC). Real-world data on oncological outcome after AA are scarce. The current study assesses efficacy and safety of AA in mCRPC patients previously treated with docetaxel who started treatment during the Belgian compassionate use program (January 2011-July 2012).

Patients And Methods: Records from 368 patients with mCRPC from 23 different Belgian hospitals who started AA 1000mg per day with 10mg prednisone or equivalent were retrospectively reviewed (September 2013-December 2014). Prostate-specific antigen (PSA) response (decrease≥50%), time to PSA progression (increase>50% over PSA nadir in case of PSA response/>25% in absence of PSA response), time to radiographic progression (on bone scans or for soft tissue lesions using Response Evaluation Criteria In Solid Tumors 1.1), overall survival and adverse event rate (Common Terminology Criteria for Adverse Events v4.03) were analyzed. Kaplan-Meier statistics were applied.

Results: Overall, 92 patients (25%) had an Eastern Cooperative Oncology Group performance status≥2. Median age was 73 years, median PSA was 103ng/dl. PSA response was observed in 131 patients (37.4%). Median time to PSA and radiographic progression was 4.1 months (95% CI: 3.6-4.6) and 5.8 months (5.3-6.4), respectively. Median overall survival was 15.1 months (13.6-16.6). Most common grade 3 to 4 adverse events were anemia (13.9%), hypokalemia (7.3%), fatigue (6.8%), and pain (6.3%). Median duration of AA treatment was 5.3 months (interquartile range: 2.8-10.3). The main study limitation is its retrospective design.

Conclusions: These real-world data on post-docetaxel AA efficacy are in line with the COU-AA-301 trial. Importantly, incidence of severe anemia and hypokalemia is up to 50% higher than reported in previous studies.
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http://dx.doi.org/10.1016/j.urolonc.2015.12.017DOI Listing
June 2016

Implementation of geriatric assessment-based recommendations in older patients with cancer: A multicentre prospective study.

J Geriatr Oncol 2015 Sep 18;6(5):401-10. Epub 2015 Aug 18.

Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium. Electronic address:

Purpose: The main objective of this study was to describe geriatric recommendations based on a geriatric assessment (GA) and to evaluate the implementation of these recommendations.

Patients And Methods: A two-step approach of screening followed by a GA was implemented in nine hospitals in Belgium. Patients ≥ 70 years were included at diagnosis or at disease progression/relapse. Concrete geriatric recommendations were systematically documented and reported to the treating physicians and consisted of referrals to professional health care workers. Patient charts were reviewed after one month to verify which geriatric recommendations have been performed.

Results: From August 2011 to July 2012, 1550 patients were included for analysis. The median age was 77 (range: 70-97) and 57.0% were female. A solid tumour was diagnosed in 91.4% and a haematological malignancy in 8.6%. Geriatric screening with the G8 identified 63.6% of the patients for GA (n=986). A median of two geriatric recommendations (range: 1-6) were given for 76.2% (95%CI: 73.4-78.8) of the evaluable patients (n=710). A median of one geriatric recommendation (range: 1-5) was performed in 52.1% (95%CI: 48.4-55.8) of the evaluable patients (n=689). In general, 460 or 35.3% (95%CI: 32.8-38.0) of all the geriatric recommendations were performed. Geriatric recommendations most frequently consisted of referrals to the dietician (60.4%), social worker (40.3%), and psychologist (28.9%).

Conclusion: This implementation study provides insight into GA-based recommendations/interventions in daily oncology practice. Geriatric recommendations were given in about three-fourths of patients. About one-third of all geriatric recommendations were performed in approximately half of these patients.
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http://dx.doi.org/10.1016/j.jgo.2015.07.005DOI Listing
September 2015

Multicenter implementation of geriatric assessment in Belgian patients with cancer: a survey on treating physicians' general experiences and expectations.

J Geriatr Oncol 2014 Oct 29;5(4):431-8. Epub 2014 Jun 29.

Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium; Department of Oncology, KU Leuven, Leuven, Belgium. Electronic address:

Objectives: The aim of this study is to identify treating physicians' general experiences and expectations regarding geriatric assessment (GA) in older patients with cancer.

Materials And Methods: A survey was carried out in 9 Belgian hospitals, which participated in a national GA implementation project focusing on older patients with cancer. A newly developed questionnaire was completed by their treating physicians. Data collection comprised of reviewing hospital data, general respondent data, and treating physicians' general experiences and expectations regarding GA. Descriptive statistics were calculated.

Results: Eighty-two physicians from 9 hospitals participated. The GA team composition can vary substantially, with a nurse as core member. Ideally, all older patients with cancer in whom a treatment decision is necessary, should benefit from the GA. Nearly all GA domains are reported as very important. Availability of GA results can be improved. Treating physicians want geriatricians to coordinate geriatric recommendations related to the identified GA problems, and expect from trained healthcare workers (THCWs) to collect GA data, to report GA results, and to follow-up the implementation of geriatric recommendations.

Conclusion: This study identifies relevant information for improving the implementation of GA in older patients with cancer in Belgium and reveals priorities for a THCW from the treating physician's point of view. To increase the effectiveness of GA, further efforts are needed to improve the implementation of geriatric recommendations.
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http://dx.doi.org/10.1016/j.jgo.2014.06.043DOI Listing
October 2014

Weekly docetaxel in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck.

Am J Clin Oncol 2011 Oct;34(5):472-7

Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium.

Background: Single-agent docetaxel, administered as a 3-weekly infusion has encouraging clinical activity against squamous cell carcinoma of the head and neck (SCCHN). Weekly administration of docetaxel is feasible and showed a favorable toxicity profile in phase I studies. We studied a weekly docetaxel regimen in heavily pretreated patients with head and neck cancer.

Patients And Methods: A total of 30 patients with proven metastatic or recurrent SCCHN were treated with docetaxel 36 mg/m weekly for 6 weeks in an 8-week schedule. Dexamethasone 20 mg or methylprednisolone 32 mg was administered 12 and 3 hours before docetaxel. No prophylactic antibiotics or growth factors were given. The primary end point was objective response rate and the secondary end points included time to progression and overall survival.

Results: Patients received a median of 6 administrations (range, 1-27). A partial response was documented in 2 patients (6.7%). The disease control rate defined the percentage of patients with responding or stable disease was 33.3%. The median progression-free survival was 7.4 weeks (95% confidence interval, 5.5-9.3 weeks) and the median overall survival was 17.9 weeks (95% confidence interval, 10.1-25.6 weeks). There were no episodes of grade 4 neutropenia, thrombocytopenia, or nonhematological toxicity.

Conclusions: Weekly docetaxel at a dose of 36 mg/m has a mild to moderate toxicity profile in SCCHN patients. However, the response rate in predominantly pretreated patients is low and the overall survival is short.
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http://dx.doi.org/10.1097/COC.0b013e3181ec5f16DOI Listing
October 2011

Docetaxel, ifosfamide and cisplatin in solid tumour treatment: a phase I study.

Anticancer Drugs 2010 Mar;21(3):306-12

Department of Medical Oncology, Antwerp University Hospital, Edegem, Belgium.

Docetaxel, ifosfamide and cisplatin have proven activity in a broad range of solid tumours and interfere with different phases of the cell cycle. We performed a phase I study with the aim to determine the maximum tolerated dose (MTD) of docetaxel, ifosfamide and cisplatin in patients with solid tumours and to define the safety, dose-limiting toxicity (DLT) and the recommended dose and administration schedule of docetaxel, ifosfamide and cisplatin for further phase II testing. Docetaxel was given by 1-h infusion on day 1, followed by ifosfamide 1000 mg/m(2)/day as a continuous infusion for 5 days. Mesna was added at the same doses to the same infusion bag and was continued for 12 h after the end of ifosfamide. Cisplatin was administered as a 24-h infusion concomitantly with ifosfamide, but in separate infusion bags, either on day 5 (schedule A) or on day 1 (schedule B). Escalation steps were planned only for docetaxel (60, 75, 85 mg/m(2)) and cisplatin (50, 75, 100 mg/m(2)). No intrapatient dose escalation was permitted. Prophylactic ciprofloxacin was used after a protocol amendment was implemented. No prophylactic haematopoietic growth factors were used. Cycles of docetaxel, ifosfamide and cisplatin were given at 3-week intervals. Toxicity was scored according to National Cancer Institute Canada-Common Toxicity Criteria 2. The MTD was defined as the dose at which a DLT was observed in fewer than two of six patients during the first treatment cycle. In total, 85 patients received 309 cycles. Only three escalation steps could be explored and DLTs were observed at each dose level. In total, 32 patients and 49 cycles showed DLTs. Febrile neutropenia occurred in 20 patients (24%). Only two DLTs were nonhaematological (one cerebral infarction and one encephalopathy grade 4). Neutropenia grade 4 lasted for greater than 7 days and/or thrombocytopenia grade 4 was dose limiting in 10 patients. Febrile neutropenia occurred in five of 41 patients (12%) who received prophylactic ciprofloxacin and in 15 of 44 patients (34%) who did not. MTD was reached at level 3 (docetaxel, 75 mg/m(2) and cisplatin, 75 mg/m(2)). With a lower dose of docetaxel (60 mg/m(2)) both schedules A and B were feasible, although, overall, schedule A seemed to be better tolerated. On the basis of this phase I study, the recommended docetaxel, ifosfamide and cisplatin regimen is docetaxel (60 mg/m(2)) on day 1, ifosfamide (1000 mg/m(2)/day) on days 1-5 and cisplatin (75 mg/m(2)) given on day 5. It is associated with substantial haematological toxicity, but this is feasible provided prophylactic antibiotics are used.
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http://dx.doi.org/10.1097/CAD.0b013e3283349994DOI Listing
March 2010

A phase I study of bendamustine hydrochloride administered once every 3 weeks in patients with solid tumors.

Anticancer Drugs 2007 Jun;18(5):587-95

Department of Medical Oncology, University Hospital Antwerp, Belgium.

The present phase I trial was planned to assess the maximum tolerated dose, the dose-limiting toxicity and the pharmacokinetics of bendamustine hydrochloride in a once every 3 weeks schedule, and to recommend a safe dose for future phase II studies. Included were patients with refractory solid tumors. Bendamustine hydrochloride was administered as a short intravenous infusion over 30 min. The starting dose was defined at 160 mg/m2 and dose escalation used increments of 20 mg/m2. Plasma and urine samples were analyzed using validated high-pressure liquid chromatography/fluorescence assays. Twenty-six patients (14 men, 12 women) were enrolled for the study. At 280 mg/m2, one out of four patients developed a thrombocytopenia grade 4, two experienced grade 3 fatigue and three experienced cardiac toxicity (grade 2). The latter toxicity was considered dose limiting also and further dose escalation was stopped. Plasma pharmacokinetics parameters of bendamustine hydrochloride and its metabolites were assessed in 15 patients. Mean pharmacokinetic parameters of bendamustine hydrochloride were a tmax of 32.3 min, a t1/2 of 37.8 min, a volume of distribution of 14.2 l/m and a clearance of 287.8 ml/min/m2. No dose dependency of bendamustine hydrochloride was observed within the used dose range. The metabolites comprised only 23% of the overall area under the concentration-time curve. The maximum tolerated dose of bendamustine hydrochloride on day 1 q 3 weeks is 280 mg/m2. Fatigue and cardiac toxicity were dose limiting. The plasma pharmacokinetics data of bendamustine and its metabolites were in accordance with previous reports. The recommended dose for future trials is 260 mg/m2 every 3 weeks.
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http://dx.doi.org/10.1097/CAD.0b013e3280149eb1DOI Listing
June 2007