Randomized phase 3 noninferiority trial of radiotherapy and cisplatin vs radiotherapy and cetuximab after docetaxel-cisplatin-fluorouracil induction chemotherapy in patients with locally advanced unresectable head and neck cancer.

Objectives: Concurrent chemoradiotherapy is the standard treatment for patients with unresectable, locally advanced squamous cell carcinoma of the head and neck (LA-SCCHN); induction chemotherapy (ICT) may provide survival benefits in some patients. This study aimed to demonstrate the noninferiority of concomitant cetuximab plus radiotherapy (cet+RT) vs cisplatin plus radiotherapy (cis+RT) in patients with unresectable LA-SCCHN who were responsive to ICT.

Materials And Methods: This randomized, open-label, phase 3 trial studied patients with unresectable LA-SCCHN who received 3 cycles of ICT (docetaxel, cisplatin, and 5-fluorouracil; TPF) followed by cis+RT (standard arm) or cet+RT (experimental arm).

Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): An update on 107 randomized trials and 19,805 patients, on behalf of MACH-NC Group.

Background And Purpose: The Meta-Analysis of Chemotherapy in squamous cell Head and Neck Cancer (MACH-NC) demonstrated that concomitant chemotherapy (CT) improved overall survival (OS) in patients without distant metastasis. We report the updated results.

Materials And Methods: Published or unpublished randomized trials including patients with non-metastatic carcinoma randomized between 1965 and 2016 and comparing curative loco-regional treatment (LRT) to LRT + CT or adding another timing of CT to LRT + CT (main question), or comparing induction CT + radiotherapy to radiotherapy + concomitant (or alternating) CT (secondary question) were eligible.

Targeted Therapy in Locally Advanced and Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (LA-R/M HNSCC).

Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemoradiotherapy is an alternative for patients with locally advanced disease. In recurrent/metastatic disease and after progression to platin-based regimens, no standard treatments other than best supportive care are currently available.

Taxane-cisplatin-fluorouracil as induction chemotherapy in locally advanced head and neck cancers: an individual patient data meta-analysis of the meta-analysis of chemotherapy in head and neck cancer group.

PURPOSE Cisplatin plus fluorouracil (PF) induction chemotherapy has been compared with taxane (docetaxel or paclitaxel), cisplatin, and fluorouracil (Tax-PF) in randomized trials in locoregionally advanced head and neck cancers (LAHNCs). The aim of this meta-analysis was to study the efficacy and toxicity of Tax-PF and PF and identify differences in outcomes in subsets of patients. METHODS Five randomized trials representing 1,772 patients were identified.

Pemetrexed in combination with cisplatin versus cisplatin monotherapy in patients with recurrent or metastatic head and neck cancer: final results of a randomized, double-blind, placebo-controlled, phase 3 study.

Background: Recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN) is associated with poor survival. Platinum-based chemotherapy is often a first-line treatment. Pemetrexed has shown single-agent activity in SCCHN and in combination with cisplatin for other tumors.

Update on the diagnosis of cancer of unknown primary (CUP) origin.

The cancer of unknown primary (CUP) concept encompasses a heterogeneous group of cancers that are difficult to diagnose and that show diverse clinical and histopathological features. Currently, CUP is the fifth most frequent cancer diagnosis in women and the eighth in men. The ongoing development of new therapies specific to the various cancer types makes mandatory the identification of the primary tumour in CUP patients, so that they may benefit from advances in therapy and improvements in prognosis.

Diagnosis of unknown primary cancer based on molecular techniques may influence therapeutic approach and improve survival.

Unknown primary cancer (UPC) is a common clinical syndrome classically associated with a poor prognosis. Pathological examination including immunohistochemistry continues to be essential in tumour origin characterization, although in many cases primary tumour site remains unknown. Gene expression based analysis may offer important diagnostic information that could lead to therapeutic decisions.

Tyrosine kinase inhibitors in treating soft tissue sarcomas: sunitinib in non-GIST sarcomas.

Sarcomas are uncommon malignancies that represent more than 50 different tumor types. Surgery remains the mainstay of treating localised disease. Anthracycline and ifosfamide-based chemotherapy is an option for advanced disease; however, effective treatment of advanced soft tissue sarcoma remains a challenge.

Pre-treatment serum lactate dehydrogenase level is an important prognostic factor in high-grade extremity osteosarcoma.

Background: Treatment of high-grade osteosarcoma remains a challenge. The prognostic significance of the pre-treatment serum lactate dehydrogenase (LDH) level is currently controversial.

Patients And Methods: We reviewed records from all patients diagnosed with conventional high-grade osteosarcoma at our institution over a 25-year period and analysed the prognostic significance of LDH in high-grade localised extremity osteosarcomas treated with chemotherapy.

Platinum-based chemotherapy plus cetuximab in head and neck cancer.

Background: Cetuximab is effective in platinum-resistant recurrent or metastatic squamous-cell carcinoma of the head and neck. We investigated the efficacy of cetuximab plus platinum-based chemotherapy as first-line treatment in patients with recurrent or metastatic squamous-cell carcinoma of the head and neck.

Methods: We randomly assigned 220 of 442 eligible patients with untreated recurrent or metastatic squamous-cell carcinoma of the head and neck to receive cisplatin (at a dose of 100 mg per square meter of body-surface area on day 1) or carboplatin (at an area under the curve of 5 mg per milliliter per minute, as a 1-hour intravenous infusion on day 1) plus fluorouracil (at a dose of 1000 mg per square meter per day for 4 days) every 3 weeks for a maximum of 6 cycles and 222 patients to receive the same chemotherapy plus cetuximab (at a dose of 400 mg per square meter initially, as a 2-hour intravenous infusion, then 250 mg per square meter, as a 1-hour intravenous infusion per week) for a maximum of 6 cycles.

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).

Primary pulmonary artery sarcoma: report of three cases and review of the literature.

Pulmonary artery sarcomas (PASs) are rare tumors of the vasculature of the lung that usually present as a thromboembolism. Failure of anticoagulant therapy to relieve all of a patient's symptoms suggests the diagnosis. Approximately 75% of patients with PAS present with dyspnea, and slightly > 50% also experience chest pain or cough.

Molecular biology in head and neck cancer.

Major changes in the treatment of head and neck cancer are possible today because of the knowledge that we have on the molecular biology of these tumors. Different pathways are active in the development of this cancer and field cancerization is a major problem for the cure in early stage disease. Epidermal growth factor signal transduction pathway is now the principal target for this disease.

Cetuximab in squamous cell carcinoma of the head and neck.

Surgery and radiotherapy are the standard treatment options for patients with squamous cell carcinoma of the head and neck (SCCHN). Chemotherapy and chemoradiotherapy are new alternatives for locally advanced disease, particularly induction chemotherapy for patients with unresectable tumors. In recurrent/metastatic disease and after progression to platin-based regimens, no treatments other than best supportive care are currently available.

DNA-repair gene polymorphisms predict favorable clinical outcome among patients with advanced squamous cell carcinoma of the head and neck treated with cisplatin-based induction chemotherapy.

Purpose: Cisplatin kills tumor cells through DNA cross linking. Alterations in the function of DNA repair genes may affect DNA repair proficiency and influence cancer patients' response to cisplatin. We studied whether single nucleotide polymorphisms (SNPs) of DNA repair genes predict the response to cisplatin or prognosis in patients with squamous cell carcinoma of the head and neck (SCCHN).

Breast cancer-specific mRNA transcripts presence in peripheral blood after adjuvant chemotherapy predicts poor survival among high-risk breast cancer patients treated with high-dose chemotherapy with peripheral blood stem cell support.

Purpose: To study the prognostic significance of the presence of breast cancer-specific mRNA transcripts in peripheral blood (PB), defined by serial analysis of gene expression, in high-risk breast cancer (HRBC) patients undergoing high-dose chemotherapy after receiving adjuvant chemotherapy.

Methods: From 1994 to 2000, 84 HRBC patients (median age, 44 years; > 10 nodes; 74%) received adjuvant chemotherapy (fluorouracil, epirubicin, and cyclophosphamide for six cycles [83%] or doxorubicin and cyclophosphamide followed by paclitaxel) before undergoing one course of cyclophosphamide plus thiotepa plus carboplatin (STAMP V). Radiotherapy or hormone therapy was administered whenever indicated.

Phase I/II study of cetuximab in combination with cisplatin or carboplatin and fluorouracil in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Purpose: This was an open, randomized, multicenter, phase I/II study to investigate the safety and tolerability of cetuximab in the first-line treatment of recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN).

Patients And Methods: Treatment comprised cetuximab (initial dose 400 mg/m2 with subsequent weekly doses of 250 mg/m2) in combination with 3-week cycles of either cisplatin (100 mg/m2) or carboplatin (area under the curve, 5), each in combination with a 5-day infusion of fluorouracil (FU) at escalating doses of 600, 800, and 1,000 mg/m2/d. The study was divided into two phases: A, the first two cycles (6 weeks) focusing on the safety and tolerability of combination therapy; and B, the remaining time for those benefiting from therapy until disease progression or intolerable toxicity.

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

Background: The objective of this study was to assess the antitumor activity and toxicity profile of weekly docetaxel in patients with recurrent or metastatic squamous cell carcinoma of the head and neck.

Methods: Patients with recurrent, metastatic, incurable squamous cell carcinoma of the head and neck were enrolled. Weekly docetaxel (30 mg/m2) was administered for 4 weeks every 5 weeks for a maximum of 6 cycles.

Phase III study comparing cisplatin plus fluorouracil to paclitaxel, cisplatin, and fluorouracil induction chemotherapy followed by chemoradiotherapy in locally advanced head and neck cancer.

Purpose: To compare the antitumor activity and toxicity of the two induction chemotherapy treatments of paclitaxel, cisplatin, and fluorouracil (FU; PCF) versus standard cisplatin and FU (CF), both followed by chemoradiotherapy (CRT), in locally advanced head and neck cancer (HNC).

Patients And Methods: Eligibility criteria included biopsy-proven, previously untreated, stage III or IV locally advanced HNC. Patients received either CF (cisplatin 100 mg/m2 on day 1 plus FU 1000 [corrected] mg/m2 continuous infusion on days 1 through 5) or PCF (paclitaxel 175 mg/m2 on day 1, cisplatin 100 mg/m2 on day 2, and FU 500 mg/m2 continuous infusion on days 2 through 6); both regimens were administered for three cycles every 21 days.

Phase II multicenter study of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory metastatic and/or recurrent squamous cell carcinoma of the head and neck.

Purpose: To evaluate the efficacy and safety of the antiepidermal growth factor receptor monoclonal antibody cetuximab in combination with platinum-based chemotherapy in patients with platinum-refractory recurrent or metastatic squamous cell carcinoma of the head and neck (SCCHN).

Patients And Methods: Ninety-six eligible patients received cetuximab (initial dose of 400 mg/m2 followed by subsequent weekly doses of 250 mg/m2) followed by platinum chemotherapy at the same dose and schedule at which progressive disease was documented before entry onto the study.

Results: The response rate, based on an independently read assessment, in the intent-to-treat population was 10%, with a disease control rate (complete response, partial response [PR], and stable disease) of 53%.

Prognostic value of the epidermal growth factor receptor (EGRF) and p53 in advanced head and neck squamous cell carcinoma patients treated with induction chemotherapy.

We measured the expression of the p53 nuclear protein and epidermal growth factor receptor (EGFR) in 46 biopsy samples from patients with advanced head and neck cancer treated with induction combination chemotherapy of 5-fluorouracil, cisplatin, and paclitaxel. Tumour expression of p53 protein was analysed with the monoclonal D07 antibody and EGFR with monoclonal H11 antibody. The overall response, defined as complete (CR) and partial response (PR) rates to treatment, was 88%.

Cyclin A as a predictive factor for chemotherapy response in advanced head and neck cancer.

Purpose: Overall survival of head and neck squamous cell cancer (HNSCC) patients has not improved despite advances in our understanding of the biology and molecular features of this disease. In particular, patients with advanced HNSCC have the poorest prognosis. To understand more about the contribution of cell cycle alterations to HNSCC development and their possible value in predicting prognosis and response to chemotherapy, we evaluated the levels of proteins involved in cell cycle control in patients diagnosed with advanced HNSCC.

Phase II trial of vinorelbine tartrate in patients with treatment-naive metastatic melanoma.

Metastatic melanoma carries a dismal prognosis and there is a need to develop new treatment strategies. Vinca alkaloids have shown consistent activity in melanoma patients, as monotherapy and as part of combination regimens. The current study evaluates the clinical activity and tolerability of vinorelbine as first-line monotherapy in patients with metastatic melanoma.

Phase II trial of dose-dense paclitaxel, cisplatin, 5-fluorouracil, and leucovorin with filgrastim support in patients with squamous cell carcinoma of the head and neck.

Background: The current study evaluated the feasibility and clinical activity of a combination of paclitaxel, cisplatin, 5-fluorouracil (5-FU), and leucovorin administered on a biweekly schedule to patients with recurrent or unresectable squamous cell carcinoma of the head and neck (HNSCC).

Methods: Patients with recurrent or unresectable HNSCC were eligible if they had received a previous regimen of neoadjuvant chemotherapy, concurrent chemoradiotherapy, or no previous systemic therapy. Patients received paclitaxel (175 mg/m2 on Day 1), cisplatin (35 mg/m2 on Days 1 and 2), leucovorin (200 mg/m2 on Day 1), and 5-FU (1000 mg/m2 per day as a 48-hour continuous intravenous infusion on Days 1 and 2) every 2 weeks.

Dose and dose intensity effect of adjuvant anthracycline-based chemotherapy in early breast cancer: a retrospective analysis.

The purpose of this study was to determine the importance of the dose of adjuvant chemotherapy in patients with breast cancer, and to determine which variables had influence on the dose of chemotherapy received. We reviewed the records of 196 patients with node-positive breast carcinoma that were treated with anthracycline-based adjuvant chemotherapy. We analyzed the influence on treatment efficacy of the dose of anthracyclines (total dose and dose intensity), and a multivariate analysis was performed to identify independent prognostic factors of chemotherapy total dose.