Neoadjuvant chemotherapy in head and neck cancer: should it be revisited?

Locally advanced SCCHN (LA-SCCHN) is generally treated by a combination of chemotherapy, irradiation and/or surgery. Timing of the chemotherapy has for long been a matter of debate but concurrent chemoradiation was widely adopted as standard of care for locally advanced squamous cell carcinoma of the head and neck after the publication of a large meta-analysis which demonstrated that concurrent chemoradiation confers an absolute survival benefit of 8% at 2 and 5 years. Induction chemotherapy has some appealing advantages including the opportunity of assessing tumor response and selecting the patients who are candidates for organ preservation.

Review: implications of in vitro research on the effect of radiotherapy and chemotherapy under hypoxic conditions.

As it is now well established that human solid tumors frequently contain a substantial fraction of cells that are hypoxic, more and more in vitro research is focusing on the impact of hypoxia on the outcome of radiotherapy and chemotherapy. Indeed, the efficacy of irradiation and many cytotoxic drugs relies on an adequate oxygen supply. Consequently, hypoxic regions in solid tumors often contain viable cells that are intrinsically more resistant to treatment with radiotherapy or chemotherapy.

The value of the Van Nuys Prognostic Index in ductal carcinoma in situ of the breast: a retrospective analysis.

The Van Nuys Prognostic Index 1996 (VNPI), based upon tumor size, pathological grade and tumor margins, is a guideline for the treatment of ductal carcinoma in situ (DCIS). It was thought to strongly decrease overtreatment. In 2003, age was added to the index as a fourth prognostic factor.

Osteonecrosis of the jaw related to the use of bisphosphonates.

Purpose Of Review: Osteonecrosis of the jaw associated with the use of potent nitrogen containing bisphosphonates is a new and challenging clinical entity with a high impact on quality of life. This review attempts to consolidate the rapidly expanding literature into practical guidelines and provides expert consensus for areas of uncertainty.

Recent Findings: Diagnostic criteria and a staging system for osteonecrosis of the jaw have been proposed, and histomorphologic analysis has confirmed osteonecrosis of the jaw as a proper disease, distinctively different from osteoradionecrosis.

Evaluation of oral versus intravenous dose of vinorelbine to achieve equivalent blood exposures in patients with solid tumours.

Patient's preference is for oral chemotherapy when both oral and i.v. are available, provided that efficacy is equivalent.

Open-label, uncontrolled, multicenter phase II study to evaluate the efficacy and toxicity of cetuximab as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck who failed to respond to platinum-based therapy.

Purpose: To evaluate the efficacy and safety of the epidermal growth factor receptor-directed monoclonal antibody cetuximab administered as a single agent in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) who experience disease progression on platinum therapy.

Patients And Methods: An open-label multicenter study in which patients with disease progression on two to six cycles of platinum therapy received single-agent cetuximab (initial dose 400 mg/m2 followed by subsequent weekly doses of 250 mg/m2) for > or = 6 weeks (single-agent phase). Patients who experienced disease progression could receive salvage therapy with cetuximab plus platinum (combination-therapy phase).

A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours.

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.

Clinical phase I and pharmacology study of gemcitabine (2', 2'-difluorodeoxycytidine) administered in a two-weekly schedule.

Gemcitabine (dFdC) was tested in a Phase I trial at 14 doses (40-5700 mg/m(2)), administered every 2 weeks as a (1/2) -h infusion to 52 patients with refractory solid cancer. Gemcitabine and its deaminated metabolite difluorodeoxyuridine (dFdU), measured with HPLC, reached plasma peak levels of 2-3 microM at 40 mg/m(2) which increased to 512 microM at 5700 mg/m(2). Gemcitabine was eliminated rapidly with a t(1/2) beta of 2.

Oncology for medical students: a European School of Oncology contribution to undergraduate cancer education.

Worldwide undergraduate cancer medicine is taught in a non-unanimous manner. There are frequent overlaps, omissions and discrepancies in the curricula of different medical schools concerning oncology teaching. Various attempts for possible changes and improvements have been made.

The role of taxanes and targeted therapies in locally advanced head and neck cancer.

Purpose Of Review: This review presents new data on the role of taxanes and targeted therapies in the management of squamous cell carcinoma of the head and neck.

Recent Findings: Taxane-containing triplets are clearly superior as an induction regimen in locally advanced squamous cell carcinoma of the head and neck when compared with cisplatin/5 fluorouracil which has been the standard for two decades. Preliminary data suggest that the addition of a taxane to cisplatin/5 fluorouracil as induction regimen followed by chemoradiation may be superior to chemoradiation alone.

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

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.

Success predictors of adjuvant chemotherapy in node-negative breast cancer patients under 55 years.

Background: Adjuvant systemic chemotherapy (ASCT) in lymph node-negative breast (LN-) cancers improves survival. The majority of (LN-) patients receive ASCT when the St. Gallen criteria or its modifications are used, as accurate identifiers which patients benefit from ASCT are lacking.

A randomized multi-center phase II trial of the angiogenesis inhibitor Cilengitide (EMD 121974) and gemcitabine compared with gemcitabine alone in advanced unresectable pancreatic cancer.

Background: Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer. In this study, the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer.

Methods: A multi-national, open-label, controlled, randomized, parallel-group, phase II pilot study was conducted in 20 centers in 7 countries.

The prognostic value of proliferation in lymph-node-negative breast cancer patients is age dependent.

In lymph-node-negative invasive breast cancer patients<55 years, the proliferation marker mitotic activity index (MAI) has previously been shown to be the strongest prognosticator. In studies without age definition, MAI was not strongly prognostic. We investigated the age dependency of the prognostic value of proliferation for distant metastasis-free (MFS) and overall cancer-related survival (OS) in 1004 histologically diagnosed T1-3N0M0 invasive breast cancers (n=516, <55 years; n=322, 55-70 years; n=166, >70 years) without systemic adjuvant therapy and long follow-up (median: 108 months).

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.

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.

The male factor in cervical carcinogenesis: a questionnaire study of men's awareness in primary care.

Background: The incorporation of testing for human papillomavirus into protocols for cervical cancer screening has far-reaching consequences for counseling patients. The sexual transmission of HPV implies the recognition of sexual behavior of both men and women as a risk factor for cervical cancer. The aim of this study was to investigate which knowledge men have of the relation of HPV and cervical cancer.

Adjuvant therapy in patients with resected poor-risk head and neck cancer.

In patients with locally or regionally advanced head and neck carcinomas, postoperative radiotherapy has historically been the adjuvant therapy applied for patients with prognostically worrisome pathologic features. Any improvement in therapeutic index achieved by adding cytotoxic agents to postoperative radiotherapy remained controversial. However, two recent randomized trials, conducted in parallel in Europe and the United States, produced level I evidence regarding improved efficacy in this setting for the concurrent administration of chemotherapy and radiotherapy.

The relation between deoxycytidine kinase activity and the radiosensitising effect of gemcitabine in eight different human tumour cell lines.

Background: Gemcitabine (dFdC) is an active antitumour agent with radiosensitising properties, shown both in preclinical and clinical studies. In the present study, the relation between deoxycytidine kinase (dCK) activity and the radiosensitising effect of gemcitabine was investigated in eight different human tumour cell lines.

Methods: Tumour cells were treated with dFdC (0-100 nM) for 24 h prior to radiotherapy (RT) (gamma-Co60, 0-6 Gy, room temperature).

The role of hysterotomy in the management of gestational trophoblastic neoplasia.

The management of late gestational trophoblastic disease recurrence is challenging. We present a case of a 16-year-old woman who was diagnosed with a gestational trophoblastic neoplasia 14 months after her hydatidiform mole pregnancy. A staging was performed revealing only an intramural lesion, which resembled a myoma, in the fundus of the uterus.

Taxanes in head and neck cancer.

Paclitaxel and docetaxel are cytotoxic agents that act on the microtubule system and cause cell death. They are active in patients with squamous cell carcinoma of the head and neck region. They can be combined with other cytotoxic agents and radiotherapy with acceptable toxicity.

Comparison of three commonly used PCR-based techniques to analyze MSI status in sporadic colorectal cancer.

Several retrospective studies have shown that a high level of microsatellite instability (MSI-H) is an important prognostic factor of a more favorable outcome in stage II and III colorectal cancer (CRC) patients. In this study, three commonly used polymerase chain reaction (PCR)-based MSI analysis techniques were compared (polyacrylamide gel electrophoresis followed by silver-staining [SSPAGE], fluorescence capillary electrophoresis [FCE], and denaturing high-performance liquid chromatography [DHPLC]) on a limited group of CRC patients, to identify the most optimal detection technique. Pathology blocks of 26 CRC patients were subjected to microdissection and the Bethesda reference panel was used for MSI analysis.