Jaap Verweij

Importance: Patients with soft tissue sarcoma are at risk for local recurrence and distant metastases despite optimal local treatment. Preoperative anthracycline plus ifosfamide chemotherapy improves outcome in common histological subtypes.

Objective: To analyze whether the previously reported improvement in local progression-free survival by adding regional hyperthermia to neoadjuvant chemotherapy translates into improved survival.

Design, Setting, and Participants: Open-label, phase 3 ...

BACKGROUND: Effective targeted treatment is unavailable for most sarcomas and doxorubicin and ifosfamide-which have been used to treat soft-tissue sarcoma for more than 30 years-still have an important role. Whether doxorubicin alone or the combination of doxorubicin and ifosfamide should be used routinely is still controversial. We assessed whether dose intensification of doxorubicin with ifosfamide improves survival of patients with advanced soft-tissue sarcoma compared with ...

BACKGROUND: The optimum treatment for high-risk soft-tissue sarcoma (STS) in adults is unclear. Regional hyperthermia concentrates the action of chemotherapy within the heated tumour region. Phase 2 studies have shown that chemotherapy with regional hyperthermia improves local control compared with chemotherapy alone. We designed a parallel-group randomised controlled trial to assess the safety and efficacy of regional hyperthermia with chemotherapy.

METHODS: Patients were recruited to ...

Most gastrointestinal stromal tumors (GISTs) harbor oncogenic mutations in KIT or platelet-derived growth factor receptor-α. However, a small subset of GISTs lacks such mutations and is termed ‘wild-type GISTs’. Germline mutation in any of the subunits of succinate dehydrogenase (SDH) predisposes individuals to hereditary paragangliomas and pheochromocytomas. However, germline mutations of the genes encoding SDH subunits A, B, C or D (SDHA, SDHB, SDHC or SDHD; collectively SDHx) are also ...

BACKGROUND: 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.

PATIENTS AND METHODS: Eligibility criteria included written informed consent, a WHO ...

PURPOSE: In in vitro studies, synergism and sequence-dependent effects were reported for the combination of topotecan and cisplatin. Recently, an oral formulation of topotecan became available. This phase I study was performed to assess the feasibility of the combination of oral topotecan and cisplatin, the pharmacokinetic interaction, and sequence-dependent effects.

PATIENTS AND METHODS: Topotecan was administered orally (PO) daily for 5 days in escalating doses and cisplatin was given ...

CAELYX/DOXIL, pegylated liposomal doxorubicin, has shown antitumour activity and reduced toxicity compared with standard doxorubicin in other tumour types. In this prospective randomised trial, 94 eligible patients with advanced soft-tissue sarcoma (STS) were treated, 50 with CAELYX (50 mg/m(2) by a 1 h intravenous (i.v.) infusion every 4 weeks) and 44 with doxorubicin (75 mg/m(2) by an i.v. bolus every 3 weeks). Histological subtypes were evenly matched, 33% were leiomyosarcoma (CAELYX: ...

Epithelial ovarian cancer is the most lethal gynecological malignancy in the Western world. A major impediment for the successful treatment is the development of drug resistance. The molecular processes that contribute to resistance have been extensively studied; however, there is not much known about regulation by microRNAs (miRNAs). We compared miRNA expression profiles of an isogenic cisplatin-sensitive and -resistant ovarian cancer cell line pair (A2780/A2780 DDP) and found 27 miRNAs ...

BACKGROUND: Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics: both tumour shrinkage (objective response) and disease progression are useful endpoints in clinical trials. Since RECIST was published in 2000, many investigators, cooperative groups, industry and government authorities have adopted these criteria in the assessment of treatment outcomes. However, a number of questions and issues have arisen which have led to ...

BACKGROUND: Irinotecan is a topoisomerase I inhibitor that has been approved for use as a first- and second-line treatment for colorectal cancer. The response to irinotecan is variable, possibly because of interindividual variation in the expression of the enzymes that metabolize irinotecan, including cytochrome P450 3A4 (CYP3A4) and uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1). We prospectively explored the relationships between CYP3A phenotype, as assessed by erythromycin ...

Previous clinical investigations with doxorubicin indicated that modulators of P-glycoprotein dramatically decrease the systemic clearance of the drug, which complicates the interpretation of toxicity and response data. In the present study, we examined the pharmacokinetics of doxorubicin and GF120918, a novel potent P-glycoprotein inhibitor, in cancer patients in a search for more selective modulation of multidrug resistance (MDR). Seven cohorts (46 patients) received sequential ...

AIMS: The histopathological diagnosis of gastrointestinal stromal tumours (GIST) is typically made based on a combination of clinical and morphological features supported by immunohistochemistry studies. The aim of this study was to examine the staining quality, sensitivity, specificity and utility of antibodies used commonly in GIST diagnosis.

METHODS AND RESULTS: Immunohistochemistry with a panel of antibodies [CD117, DOG1, protein kinase C (PKC)-theta, nestin, CD34, smooth muscle ...