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ABSTRACT: The purpose of this study was to analyse retrospectively the intensity-modulated radiotherapy (IMRT) results in patients with head and neck cancer (HNC) treated between November 2003 and June 2007.
Patients with early and locoregionally advanced HNC were treated with inverse-planned step-and-shoot IMRT. The prescribed dose varied from 66 Gy to 70 Gy in those receiving IMRT as definitive treatment and from 60 Gy to 70 Gy in the post-operative setting. IMRT was given alone, after induction chemotherapy (ICT), with concomitant chemotherapy (CRT) or with both. Acute and late toxicities are reported; locoregional control (LRC), locoregional relapse-free survival (LRRFS) and overall survival (OS) were calculated from the start of radiation.
IMRT was used in 78 patients (48 as definitive treatment, 30 post-operatively), of whom 20 also received ICT and 35 CRT. Three patients stopped IMRT early, one for toxicity (mucosa). Acute toxicity scoring revealed 5 cases (6%) of severe skin toxicity and 65 cases (83%) of severe mucosal toxicity. After a median follow-up of 18.7 months, late toxicities included xerostomia (44%), loss of taste (14%) and fibrosis of the neck (9%). 16 patients had died, of whom 10 due to tumour recurrence/progression and 2 due to treatment (but not IMRT related). The LRC, LRRFS and OS at 3 years are 66.1%, 48.5% and 60.3% in the definitive IMRT group and 85.4%, 82.5% and 85.9% in the post-operative setting, respectively.
We consider IMRT for locoregional HNC feasible not only as a single modality but also after surgery, after induction chemotherapy and concurrently with chemotherapy.
The British journal of radiology 04/2011; 84(1000):367-74. · 2.11 Impact Factor
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ABSTRACT: Radiotherapy (RT) with concurrent chemotherapy is the current standard of care for patients with unresectable locally advanced squamous cell carcinoma of the head and neck (SCCHN). Gemcitabine (GEM) is a potent radiosensitizer and in addition has activity as an anticancer agent in SCCHN.
Twenty-six patients with locally far advanced SCCHN were enrolled in a chemoradiation feasibility study between November 1998 and September 2003. Use was made of conventionally fractionated RT and GEM 100 mg/m(2), which was given within 2 h prior to radiotherapy on a weekly basis starting on day 1 of RT. Response was assessed according to WHO criteria, toxicity according to NCI-CTC version 2.
The patients received a median of 7 (2-8) weekly cycles of gemcitabine and a median cumulative RT dose of 70 Gy (66-84.75). Hematologic toxicity was mild, but non-hematologic toxicity was severe: grade 3-4 stomatitis occurred in 85% of patients, dermatitis in 69%, pharyngitis/esophagitis in 81% and 80% of the patients needed a feeding tube during treatment. All 22 evaluable patients responded (50% complete, 50% partial). Median follow up of the surviving patients is 46 months. Median disease-free and overall survival is 13 months and 19 months, respectively; 27% of the patients are alive without evidence of recurrence beyond 3 years.
Conventionally fractionated RT in combination with GEM 100 mg/m(2) weekly is feasible and highly active in the treatment of locally advanced SCCHN. In particular, long-term local control rate is promising. Acute mucosal toxicities are significant but manageable. Long-term toxicity interferes with normal food intake.
Annals of Oncology 12/2007; 18(11):1856-60. · 6.43 Impact Factor
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ABSTRACT: The aim of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and the pharmacokinetic profile (Pk) of bendamustine (BM) on a day 1 and 2 every 3 weeks schedule and to recommend a safe phase II dose for further testing. Patients with solid tumours beyond standard therapy were eligible. A 30-min intravenous infusion of BM was administered d1+d2 q 3 weeks. The starting dose was 120 mg m(-2) per day and dose increments of 20 mg m(-2) were used. Plasma and urine samples were analysed using validated high-performance liquid chromatography/fluorescence assays. Fifteen patients were enrolled. They received a median of two cycles (range 1-8). The MTD was reached at the fourth dose level. Thrombocytopaenia (grade 4) was dose limiting in two of three patients at 180 mg m(-2). One patient also experienced febrile neutropaenia. Lymphocytopaenia (grade 4) was present in every patient. Nonhaematologic toxicity including cardiac toxicity was not dose limiting with this schedule. Mean plasma Pk values of BM were tmax 35 min, t(1/2) 49.1 min, Vd 18.3 l m(-2), and clearance 265 ml min(-1) m(-2). The mean total amount of BM and its metabolites recovered in the first micturition was 8.3% (range 2.7-26%). The MTD of BM in the present dose schedule was 180 mg m(-2) on day 1+2. Thrombocytopaenia was dose limiting. The recommended dose for future phase II trials with this schedule is 160 mg m(-2) per day.
British Journal of Cancer 07/2007; 96(11):1692-8. · 5.04 Impact Factor
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D Schrijvers,
C Van Herpen,
J Kerger,
E Joosens,
C Van Laer,
A Awada,
D Van den Weyngaert,
H Nguyen,
C Le Bouder,
J A Castelijns,
J Kaanders,
P De Mulder,
J B Vermorken
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ABSTRACT: 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 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.
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.
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.
Annals of Oncology 05/2004; 15(4):638-45. · 6.43 Impact Factor
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ABSTRACT: A patient with breast cancer developed severe asthenia, accompanied with progressively increasing transaminases, during adjuvant chemotherapy with CMF (cyclophosphamide, methotrexate and 5-fluorouracil). Additional blood tests and imaging were negative. A liver biopsy revealed a grade II toxic hepatitis. Because methotrexate was suspected to be the cause of the hepatotoxicity, the administration of this drug was stopped and mitoxantrone was given instead. A recovery of clinical symptoms and normalisation of the liver function tests was observed afterwards. In that sense, mitoxantrone appears to be a valuable alternative to methotrexate in cases of hepatotoxicity in patients with breast cancer. An overview of the literature regarding methotrexate hepatotoxicity is presented.
The Netherlands Journal of Medicine 07/2002; 60(5):216-22. · 2.07 Impact Factor
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ABSTRACT: A phase I study was performed with MEN-10755, a novel anthracycline with promising preclinical antitumour activity, in patients with solid tumours to determine the maximum tolerated dose (MTD); the dose-limiting toxicities (DLTs); to document antitumour activity; and to propose a safe dose for phase II evaluation. MEN-10755 at a starting dose of 15 mg/m2/week was given by short intravenous infusion weekly for 3 weeks and cycles were repeated every 28 days. Twenty-four patients received 55 cycles. Doses of MEN-10755 were 15, 30, 40 and 45 mg/m2. At a dose of MEN-10755 45 mg/m2, treatment could not be given as planned due to neutropenia and one patient developed a decrease in cardiac function. This dose level was considered to be the MTD. Chemotherapy-naive patients could be treated with 40 mg/m2/week, and only one DLT (grade 4 neutropenia) was observed. At that dose, three of six chemotherapy pretreated patients developed a DLT during their first treatment cycle: one patient developed a grade 4 thrombocytopenia, one patient a grade 4 neutropenia and one patient developed a grade 3 acute hypersensitivity reaction resulting in discontinuation of treatment. At this dose level, one other patient did not receive treatment on day 15 as planned due to grade 3 neutropenia. No responses were observed. MEN-107555 at a dose of 30 mg/m2/week in pretreated patients and 40 mg/m2/week in chemotherapy-naive patients for three consecutive weeks followed by 1 week rest is recommended for phase II testing.
Annals of Oncology 04/2002; 13(3):385-91. · 6.43 Impact Factor
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A M Bos,
E G de Vries,
P Dombernovsky,
S Aamdal,
D R Uges, D Schrijvers,
J Wanders,
M W Roelvink,
A R Hanauske,
S Bortini,
A Capriati,
A E Crea,
J B Vermorken
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ABSTRACT: The doxorubicin analogue MEN-10755 has been identified as a compound with promising antitumour activity based on structure-activity studies of a new series of anthracycline disaccharides. The high antitumour activity of MEN-10755 in human tumour xenografts, including doxorubicin-resistant xenografts, and its unique pharmacological and biological properties made this novel disaccharide analogue an interesting candidate for clinical evaluation. Two pharmacokinetic phase I studies with different dosing schedules were performed in adults with solid refractory malignancies. The pharmacokinetics of MEN-10755 were studied after a 15-min i.v. infusion given once every 3 weeks or once every week for 3 weeks followed by 1 week rest. Plasma and urine levels of MEN-10755 were measured by HPLC with fluorescent detection. It was possible to combine the pharmacokinetic results of the two studies because there was no accumulation of MEN-10755 before the next infusion of MEN-10755 in the weekly study with 1 week rest. The administered dose levels on day 1 in this study were all in the lower range from the 3-weekly study. The postinfusion plasma kinetics of MEN-10755 were best described by a triexponential model. The plasma peak levels (Cmax) of MEN-10755 showed a linear relationship with the administered dose. Peak plasma MEN-10755 levels ranged between 474 and 21,587 microg/l. The mean elimination half-life (T(1/2gamma)) was 20.7+/-9.0 h. The AUC(0-infinity) was proportional to the administered dose. The mean plasma clearance of MEN-10755 was 6.0+/-2.2 l/h per m2 with a mean volume of distribution (Vss) of 95.6+/-43.4 l/m2. The mean renal excretion of unchanged drug within 24 h was 4.3+/-1.8%. Compared to epirubicin and doxorubicin, the pharmacokinetics of MEN-10755 were characterized by an approximately twofold shorter terminal half-life, a much lower total plasma clearance and a much smaller volume of distribution.
Cancer Chemotherapy and Pharmacology 12/2001; 48(5):361-9. · 2.83 Impact Factor
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ABSTRACT: The pharmacokinetics of the combination of docetaxel and ifosfamide were studied in a phase I study. Docetaxel was given to cancer patients as a 1-hour infusion followed by a 24-hour infusion of ifosfamide (schedule A). After the dose-limiting toxicity of the combination was reached, ifosfamide was administered as a 24-hour infusion followed after 24 hours by a 1-hour infusion of docetaxel (schedule B). Cycle duration was 21 days. Docetaxel was determined by high-performance liquid chromatography, and ifosfamide and its metabolites, by gas chromatography-mass spectrometry. Twenty-seven patients were treated according to schedule A, and 6 according to schedule B. Combining the two drugs did not change their respective plasma half-lives. The sequence of drug administration did not affect the clearance and the area under the curve (AUC) of docetaxel. There was a decrease in the AUC of ifosfamide in schedule A compared with schedule B, resulting from an increase in the clearance of ifosfamide. The pharmacokinetics of docetaxel are not influenced by combination with ifosfamide, regardless of the drug sequence, but ifosfamide pharmacokinetics are changed by docetaxel, depending on the sequence of administration. The increase of clearance in schedule A may be due to the pretreatment with corticosteroids.
American Journal of Clinical Oncology 09/2000; 23(4):358-63. · 2.01 Impact Factor
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British Journal of Dermatology 06/2000; 142(5):1069-70. · 3.67 Impact Factor
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ABSTRACT: Chest wall invasion is found in 5% of patients with non-small-cell lung cancer. Treatment for localized non-small-cell lung cancer consists of surgical resection and/or radiotherapy. We report a patient with lung cancer who had a local relapse after a reconstruction of the thoracic wall with a soft-tissue patch. Chemotherapy was given before reresection of the local relapse. Postoperative radiation therapy was performed. Twenty-one months after treatment for recurrent disease, the patient remains in complete remission. The history of this patient shows that a soft-tissue patch may prevent local tumor invasion. A review of the literature is given.
American Journal of Clinical Oncology 03/2000; 23(1):32-3. · 2.01 Impact Factor
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ABSTRACT: Docetaxel and paclitaxel represent a new class of cytotoxic agents having both a specific chemical structure and mechanism of action. They act to promote tubulin polymerization and the formation of stable microtubules. The microtubules produced in the presence of taxoids are resistant to disassembly by physiologic stimuli, and cells exposed to these agents exhibit an accumulation of disorganized microtubule arrays. This affects the normal mitotic process and eventually results in cell death. Both drugs are active as single agents in patients with head and neck cancer with response rates ranging from 20% to 40%. They may be combined with other cytotoxic agents, radiotherapy, or both. A review is given of the presently available data.
The Oncologist 02/2000; 5(3):199-208. · 3.91 Impact Factor
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B Van den Eynden,
I Hermann, D Schrijvers,
P Van Royen,
R Maes,
L Vermeulen,
K Herweyers,
W Smits,
A Verhoeven,
R Clara,
J Denekens
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ABSTRACT: Factors determining the place of palliative care and death were studied by interviewing 40 patients using a semi-structured questionnaire. The 86 interviews assessed showed that both emotional and somatic factors played a part in the determination of whether patients were transferred and of their place of death. Emotional factors were mentioned in 41% as being of importance, and physical factors in 32%. Material and financial factors are probably underestimated owing to the methodology.
Supportive Care Cancer 02/2000; 8(1):59-64. · 2.60 Impact Factor
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ABSTRACT: Ifosfamide is an alkylating agent used in the treatment of a variety of solid tumours. Ten to 15% of patients treated with ifosfamide develop an encephalopathy. Methylene blue (MB) may be used in the treatment of this encephalopathy. The purpose of this study was to evaluate the neuroprotective effect of MB in these patients and to review the literature. Between 1993 and 1997, 52 patients (age 16-77 years) with solid tumours were treated with ifosfamide in dosages ranging from 3 to 5 g m(-2) q3w when given in combination schedules and up to 12 g m(-2) q4w when given as a single agent. Twelve patients developed central nervous system (CNS) depression, defined as National Cancer Institute Common Toxicity Criteria (NCI-CTC) neurocortical toxicity grade 2 or higher. Eight were treated with MB at a dose of 6 x 50 mg day(-1) intravenously (i.v.). Four recovered fully within 24 h, two recovered partially after 24 h and completely after 48 h while two recovered only after 72 h. Four patients did not receive MB and all recovered only after 48 h. Three patients received prophylaxis with MB at a dose of 4 x 50 mg day(-1) i.v. for the subsequent chemotherapy cycles. Two developed milder encephalopathy; one had no CNS depression at all. We conclude that MB is an effective treatment for ifosfamide-induced encephalopathy. Our findings suggest that it may also be used as a prophylactic agent.
British Journal of Cancer 02/2000; 82(2):291-4. · 5.04 Impact Factor
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Scandinavian Journal of Infectious Diseases 02/2000; 32(1):106. · 1.72 Impact Factor
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ABSTRACT: 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.
Acta chirurgica Belgica 01/2000; 99(6):312-4. · 0.43 Impact Factor
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ABSTRACT: We present the case of a patient with a locally advanced hypopharyngeal carcinoma who developed a severe cytomegalovirus (CMV) colitis after his first chemotherapy course with 5-fluorouracil (5-FU), docetaxel and cisplatin. The most probable cause of his CMV colitis is the impaired immunity during a phase of neutropenia after the chemotherapy. Although there was amelioration of the colitis and clinical status after treatment with ganciclovir, the patient later deteriorated and died due to recurrent bacterial infections. This is the third reported case of CMV colitis treated with ganciclovir in a patient with a solid tumour. It is the first report of CMV colitis after docetaxel containing chemotherapy. Although CMV colitis is most frequently observed in immunosuppressed patients such as those with acquired immune deficiency syndrome (AIDS), transplants and corticosteroid treatment, it has also been reported in less immunosuppressed (elderly, malnourished,...) and even non-immunosuppressed patients. CMV infection should therefore be included in the differential diagnosis of GI disease in all patients, and when suspected, the clinician should pursue appropriate diagnostic and therapeutic interventions.
Annals of Oncology 12/1999; 10(11):1369-72. · 6.43 Impact Factor
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ABSTRACT: Resection of bilateral pulmonary metastases is exceptional. However, in carefully selected patients extensive resections might be successfully performed. We report two patients who underwent a pneumonectomy and excision of pulmonary metastases in the other lung, via a left wedge resection for patient 1 and left segmentectomy for patient 2. Resections were carried out for metastases of a malignant fibrous histyocytoma and for a teratocarcinoma. Both patients are still alive 9 months and 4 years after their last metastasectomy, respectively.
European Journal of Surgical Oncology 11/1999; 25(5):552-3. · 2.50 Impact Factor
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ABSTRACT: 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.
Anti-Cancer Drugs 09/1999; 10(7):633-9. · 2.41 Impact Factor
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ABSTRACT: After oral or parenteral administration of chemotherapeutic agents, these drugs are transported to the tissues by the blood in different fractions: plasma water, plasma proteins or cells. In this review, the role of the red blood cell in storage, transport and metabolism of different anti-cancer drugs is described.
Anti-Cancer Drugs 03/1999; 10(2):147-53. · 2.41 Impact Factor
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ABSTRACT: Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination.
Eligibility criteria included written informed consent, a WHO performance status < 2, life expectancy of > 12 weeks, and adequate bone marrow, liver and renal function. Neoadjuvant pretreatment with cisplatin-based chemotherapy or prior radiotherapy were allowed. Patients were ineligible if pretreated with taxoids, had CNS involvement, concurrent malignancy, peripheral neuropathy, or no measurable disease. Treatment consisted of docetaxel 100 mg/m2 (one-hour i.v. infusion), followed by cisplatin 75 mg/m2 (three-hour i.v. infusion), repeated every three weeks. Supportive care included hydration, 5HT3-antagonists, and corticosteroids.
Forty-four patients (median age 55 years, range 35-76) entered the trial; 41 patients were eligible, 164 cycles of treatment were evaluable for toxicity, and 31 patients for response. Fourteen patients had undergone prior surgery, 15 had received radiotherapy, and five had had chemotherapy. A median number of four treatment cycles (range 1-6) was given. Hematologic and non-hematologic toxicities were common, but hypersensitivity reactions and fluid retention were very infrequent due to corticosteroid prophylaxis. Four patients were taken off the study due to toxicity, and one toxic death occurred due to pneumonia. Among 41 eligible patients, objective responses as confirmed by independent review included six complete remissions and 16 partial remissions, resulting in an overall response rate of 53.7% (95% confidence interval: 37.4%-69.3%). Responses occurred in locally advanced, recurrent and metastatic disease, both in pre- and non-pretreated patients. Of 22 evaluable, non-pretreated patients with locally advanced or metastatic disease, five achieved complete responses, and 14 partial responses. Observed among nine evaluable pretreated patients with locally advanced or metastatic head and neck cancer were one complete response and two partial responses.
The combination of docetaxel and cisplatin is feasible and active in locally advanced, recurrent, and metastatic squamous cell carcinoma of the head and neck.
Annals of Oncology 02/1999; 10(1):119-22. · 6.43 Impact Factor
