Intra-arterial versus intravenous chemoradiation for advanced head and neck cancer: Results of a randomized phase 3 trial.

Background: Chemoradiation is the preferred treatment for advanced stage IV head and neck cancer. Higher doses of chemotherapy yielded promising results in vitro and vivo, confirmed by intra-arterial (IA) cisplatin-based chemoradiation in phase 2 studies.

Methods: Two hundred and thirty-nine patients with (functionally) unresectable head and neck cancer were included, from 2000 to 2004, in a multicenter, randomized phase 3 trial, comparing IA and intravenous chemoradiation.

Hearing loss due to concurrent daily low-dose cisplatin chemoradiation for locally advanced head and neck cancer.

Background And Purpose: Cisplatin-based chemo-irradiation (CRT) is increasingly used for head and neck squamous cell carcinoma (HNSCC). We aimed to assess hearing deterioration due to low-dose cisplatin chemoradiation and to compare the observed hearing loss with hearing loss in our previously described high-dose cisplatin CRT cohort.

Materials And Methods: A prospective analysis of hearing thresholds at low and (ultra)-high frequencies obtained before and after treatment in 60 patients.

Prognostic value of primary tumor volume after concurrent chemoradiation with daily low-dose cisplatin for advanced-stage head and neck carcinoma.

Background: The purpose of this study was to evaluate the prognostic value of tumor volume in head and neck squamous cell carcinoma treated with chemoradiation.

Methods: Forty-six patients were treated with radiotherapy and cisplatin (6 mg/m(2) IV x 20, daily). Baseline primary tumor volume was recorded from MRI scans.

[A solitary sternal lesion found by skeletal scintigraphy following treatment for breast carcinoma].

Breast carcinoma frequently metastasises to bone, most often to the thoracic and lumbosacral spine. 3 women, aged 66, 47 and 54 years, who had been previously treated for breast cancer presented with sternal pain. Bone scintigraphy revealed a solitary sternal hot spot in all 3 patients.

Ototoxicity in a randomized phase III trial of intra-arterial compared with intravenous cisplatin chemoradiation in patients with locally advanced head and neck cancer.

Purpose: Cisplatin concomitantly administered with radiotherapy is increasingly used in locally advanced head and neck squamous cell carcinoma. We aimed to compare the incidence of hearing loss between patients treated with intra-arterial high-dose cisplatin chemoradiation with sodium thiosulfate (CRT-IA) and intravenous high-dose cisplatin chemoradiation without sodium thiosulfate (CRT-IV).

Patients And Methods: We conducted a prospective analysis of hearing thresholds at low and (ultra-) high frequencies obtained before, during, and after treatment in 158 patients.

Concurrent chemoradiation with daily low dose cisplatin for advanced stage head and neck carcinoma.

Background And Purpose: To evaluate treatment results of concurrent chemoradiation with daily low dose cisplatin.

Materials And Methods: 121 patients with advanced stage HNSCC were treated with RT (35 x 2 Gy) and cisplatin (6 mg/m(2) i.v.

Risk factors of ototoxicity after cisplatin-based chemo-irradiation in patients with locally advanced head-and-neck cancer: a multivariate analysis.

Purpose: Cisplatin chemo-irradiation is increasingly used in locally advanced squamous cell carcinoma of the head and neck. The objective of this study is to determine risk factors of ototoxicity due to intra-arterial high-dose cisplatin chemoradiation.

Methods And Materials: A prospective analysis of hearing thresholds at low and (ultra) high frequencies obtained before, during, and after treatment in 146 patients.

Relationship between clinical factors and the incidence of toxicity after intra-arterial chemoradiation for head and neck cancer.

Background And Purpose: Concomitant chemoradiation is more and more used for advanced head and neck cancer. It improves local control and survival compared to radiotherapy alone, but goes along with serious toxicity. This study was set up to determine the relationship between patient-, tumour- and treatment-related factors and acute/late toxicity after concomitant chemoradiation.

Phase II and pharmacological study of oral paclitaxel (Paxoral) plus ciclosporin in anthracycline-pretreated metastatic breast cancer.

Paclitaxel is an important chemotherapeutic agent for breast cancer. Paclitaxel has high affinity for the P-glycoprotein (P-gp) (drug efflux pump) in the gastrointestinal tract causing low and variable oral bioavailability. Previously, we demonstrated that oral paclitaxel plus the P-gp inhibitor cyclosporin (CsA) is safe and results in adequate exposure to paclitaxel.

Determinants of the elimination of methotrexate and 7-hydroxy-methotrexate following high-dose infusional therapy to cancer patients.

Aims: To characterize determinants of the elimination of methotrexate (MTX) and 7-hydroxy-methotrexate (7-OH-MTX) in patients receiving high-dose MTX therapy (HDMTX).

Methods: 24 and 48-h blood samples from 76 patients receiving HDMTX (dose range 300 mg m-2 to 12 g m-2) were analysed, and concentration-time data were subjected to population pharmacokinetic and covariate analysis using nonlinear mixed-effect modelling (NONMEM).

Results: Treatment-related mortality was 1.

Seven year update of an EORTC phase III trial of high-dose intensity M-VAC chemotherapy and G-CSF versus classic M-VAC in advanced urothelial tract tumours.

EORTC protocol 30924 is an international randomized trial reporting a 7.3 year update of a 2 weekly regimen of high-dose intensity chemotherapy with M-VAC plus granulocyte colony stimulating factor (HD-M-VAC) compared to classic M-VAC in advanced transitional cell carcinoma (TCC). Two hundred and sixty three untreated patients with bidimensionally measurable TCC were included.

Neoadjuvant methotrexate, vinblastine, doxorubicin and cisplatin for histologically proven lymph node positive bladder cancer.

Purpose: We gained insight into the effect of neoadjuvant chemotherapy and subsequent surgery in patients with bladder cancer with tumor positive lymph nodes.

Materials And Methods: A total of 52 patients with histologically proven positive lymph nodes (by lymph node dissection or aspiration cytology) were treated with chemotherapy and post-chemotherapy surgery in case of partial or complete response. We evaluated response in the primary tumor and lymph nodes, long-term clinical outcome, and clinicopathological features potentially predictive of survival.

Health-related quality of life in survivors of locally advanced breast cancer: an international randomised controlled phase III trial.

Background: Dose-intensive chemotherapy has generated much interest in the treatment of patients with locally advanced breast cancer because it might offer a survival benefit. We aimed to compare the effects of such an approach with those of standard chemotherapy on health-related quality of life (HRQOL).

Methods: 224 patients with locally advanced breast cancer were randomly assigned to 75 mg/m(2) cyclophosphamide given orally on days 1-14, and 60 mg/m(2) epirubicin and 500 mg/m(2) fluorouracil both given intravenously on days 1 and 8, for six cycles every 28 days (6 months' treatment; standard treatment) and 224 patients to 830 mg/m(2) cyclophosphamide and 120 mg/m(2) epirubicin both given intravenously on day 1, and 5 microg/kg filgrastim per day given subcutaneously on days 2-13, for six cycles every 14 days (3 months' treatment; dose-intensive treatment).

[The role of simultaneous chemotherapy and radiotherapy in the treatment of locally metastasised tumours of the larynx, pharynx and oral cavity].

In The Netherlands each year there are 2300 new patients with a squamous-cell carcinoma of the larynx, pharynx and oral cavity, and of these, one-third has a locally regionally advanced tumour. An operation can then lead to an unacceptable loss of function, whilst radiotherapy alone has no effect on survival. Compared to radiotherapy alone, the combination of radiotherapy and chemotherapy containing cisplatin, when administered simultaneously, produces a higher percentage of patients with loco-regional control and a higher 3-year survival percentage.

Pretreatment probability model for predicting outcome after intraarterial chemoradiation for advanced head and neck carcinoma.

Background: Concurrent chemoradiation is being used increasingly to treat patients with advanced-stage head and neck carcinoma. In the current study, a clinical nomogram was developed to predict local control and overall survival rates for individual patients who will undergo chemoradiation.

Methods: Ninety-two consecutive patients with UICC TNM Stage III/IV squamous cell carcinoma of the oral cavity, oropharynx, hypopharynx, and supraglottic larynx were treated with selective-targeted chemoradiation (acronym: RADPLAT).

The effect of food on the pharmacokinetics of S-1 after single oral administration to patients with solid tumors.

Purpose: The purpose is to determine the effect of food on the bioavailability of S-1, an oral formulation of the 5-fluorouracil (5FU) prodrug Ftorafur (FT), 5-chloro-2,4-dihydroxypyridine (CDHP), a dihydropyrimidine dehydrogenase inhibitor, and oxonic acid (an inhibitor of 5FU phosphoribosylation in normal gut mucosa) in a molar ratio of 1:0.4:1.

Experimental Design: Eighteen patients received a single dose of S-1 of 35 mg/m(2) with (535-885 kcal) or without food in a crossover study design: in arm A without breakfast on day -7 and with breakfast on day 0 and in arm B the reversed sequence.

High-dose superselective intra-arterial cisplatin and concomitant radiation (RADPLAT) for advanced head and neck cancer.

Background: The purpose of this study was to study the effect of intensive targeted chemoradiation in a group of patients with head and neck cancer with stage IV inoperable disease.

Methods: We examined 79 patients with inoperable stage IV head and neck cancer receiving intra-arterial infusion of high-dose cisplatin (150 mg/m(2)) on days 2, 9, 16, and 23 concomitant with delivery of external beam radiotherapy (total dose, 70 Gy; 2 Gy, 35 fractions; 1 fraction/day for 7 weeks). Sodium thiosulfate was administered intravenously to provide effective cisplatin neutralization.

Palliative chemotherapy after failure of high-dose chemotherapy in breast cancer--toxicity and efficacy.

We evaluated the toxicity and efficacy of the first palliative chemotherapy regimen after failure of high-dose chemotherapy in 148 patients with primary or metastatic breast cancer treated with high-dose chemotherapy (one full dose CTC, (cyclophosphamide 6000 mg/m2, thiotepa 480 mg/m2, carboplatin 1600 mg/m2) or multiple courses CTC or 'tiny' CTC (tCTC) (two-thirds of the agents of the full-dose regimen), all divided over 4 days). After a median follow-up time of 46.8 (range 1-120) months, 79 patients had a relapse or progressive disease and 41 patients were treated with palliative chemotherapy.

Toxicity of the high-dose chemotherapy CTC regimen (cyclophosphamide, thiotepa, carboplatin): the Netherlands Cancer Institute experience.

High-dose chemotherapy (HD-CT) has a role in the potentially curative treatment of several tumours. The relative efficacies of the different regimens have not been studied in comparative trials, but it is clear that toxicities differ significantly between them. We analysed the immediate and long-term toxicity in the first 100 consecutive patients treated with the CTC regimen (cyclophosphamide 6000 mg m(-2), carboplatin 1600 mg m(-2) (or 20 mg ml(-1) min under the curve (AUC)) both as daily 1 h infusion, thiotepa 480 mg m(-2) as twice daily 30 min infusion, all divided over 4 consecutive days) followed by peripheral blood progenitor cell reinfusion (PBPC-Tx).

Pharmacokinetics of S-1, an oral formulation of ftorafur, oxonic acid and 5-chloro-2,4-dihydroxypyridine (molar ratio 1:0.4:1) in patients with solid tumors.

S-1 is an oral formulation of ftorafur (FT), oxonic acid and 5-chloro-2,4-dihydroxypyridine (CDHP) at a molar ratio of 1:0.4:1. FT is a 5-fluorouracil (5-FU) prodrug, CDHP is a dihydropyrimidine dehydrogenase (DPD) inhibitor and oxonic acid is an inhibitor of 5-FU phosphoribosylation in the gastrointestinal mucosa and was included to prevent gastrointestinal toxicity.

Major and minor salivary glands tumours.

Malignant salivary gland tumours are rare. The most common tumour site is the parotid. Aetiologic factors are not clear.

Health-related quality-of-life assessments and patient-physician communication: a randomized controlled trial.

Context: There has been increasing interest in the use of health-related quality-of-life (HRQL) assessments in daily clinical practice, yet few empirical studies have been conducted to evaluate the usefulness of such assessments.

Objective: To evaluate the efficacy of standardized HRQL assessments in facilitating patient-physician communication and increasing physicians' awareness of their patients' HRQL-related problems.

Design: Prospective, randomized crossover trial.

Quality-of-life assessment after supradose selective intra-arterial cisplatin and concomitant radiation (RADPLAT) for inoperable stage IV head and neck squamous cell carcinoma.

Objective: To evaluate quality-of-life (QOL) aspects of an organ preservation intra-arterial chemotherapy and concomitant radiation protocol, RADPLAT.

Design: Nonrandomized phase 2B feasibility trial.

Patients: Fifty consecutive patients with inoperable stage IV head and neck cancer.

Randomized trial of high-dose chemotherapy and hematopoietic progenitor-cell support in operable breast cancer with extensive lymph node involvement: final analysis with 7 years of follow-up.

Background: The aim of this study was to present an update of overall (OS) and disease-free survival (DFS) and to evaluate the correlation between outcome and pathological findings at surgery in a randomized trial of high-dose chemotherapy following neoadjuvant chemotherapy and surgery in high-risk breast cancer patients.

Patients And Methods: Ninety-seven women <60 years of age with breast cancer and extensive axillary lymph node involvement received three courses of FE120C (5-fluorouracil 500 mg/m2, epirubicin 120 mg/m2, cyclophosphamide 500 mg/m2) followed by surgery. Eighty-one patients were randomized to receive either a fourth FE120C course alone or a fourth FE120C course followed by high-dose chemotherapy (cyclophosphamide 6 g/m2, thiotepa 480 mg/m2, carboplatin 1600 mg/m2).

Diagnosis and treatment of isolated neck metastases of adenocarcinomas.

Aims: Cervical metastases of adenocarcinoma or undifferentiated large cell carcinoma (ULCC) (non-squamous cell carcinoma) of unknown primary origin are rare and often accompanied by distant metastases at multiple sites in the body. Nevertheless, in the past decades, several patients have presented in our clinic with isolated neck metastases of this type of malignancy. The aim of our study is to evaluate the clinical behaviour of these cases and to define the role of surgery and radiotherapy.