Archive for the ‘Head & Neck Cancer’ Category

Vectibix and Chemotherapy, E7389 (Eribulin) for Treatment of Head & Neck Cancer

October 3, 2007

Advances in the management of patients with head & neck cancer (HNC) were presented at the Multidisciplinary Head and Neck Cancer Symposium, cosponsored by the American Society for Therapeutic Radiology and Oncology (ASTRO) and the American Society of Clinical Oncology(ASCO), January 18-20, 2007. Despite increasing awareness of the cancer-causing effects of tobacco, the incidence of HNC has not decreased worldwide. Efforts to prevent these tumors through drugs or treatments have largely failed, and early detection strategies have not been successful. Therefore, most patients with HNC continue to present with advanced (stages III and IV) disease.

Oral cavity tumors are treated primarily with surgical resection because of the high toxicity of radiation in this region (eg, osteoradionecrosis of the jaw). Advanced tumors of the throat and larynx are usually treated with combined modality therapy (chemoradiation [CRT]).  Surgery is often reserved for neck dissection, to manage advanced neck disease (N2 or N3 node staging) and/or to manage the neck nodes after an incomplete response in the neck to CRT. The major advance in the management of HNC was the integration of targeted new agents into current treatment regimens.

HNC cells express EGFR (epidermal growth factor receptor) at high levels compared to neighboring normal tissue cells.  High EGFR protein on the HNC cells correlate with reduced survival.  The EGFR blocking monoclonal antibody cetuximab (Erbitux) was studed in combination with radiation therapy (RT) versus RT alone in a large multicenter study.  The combination demonstrated improved disease control and survival, and this finding led to approval of this agent by the US Food and Drug Administration (FDA) in 2006 for the treatment of HNC.  Panitumumab (Vectibix)  is a fully humanized anti-EGFR monoclonal antibody.  It is also under study for treatment of HNC.   Vectibix and Erbitux have had comparable activity in metastatic colon cancer, where both are already FDA-approved.  The risks of EGFR blocking monoclonal antibodies also appear to be comparable for both cetuximab and panitumumab, including infusion reactions, rash, diarrhea, or rare drug-induced lung inflammation. 

When patients have progressed after initial CRT or surgery, they often have unresectable local disease or distant metastatic disease, such as in the lung.  Chemotherapy has been the mainstay of treatment for such patients.  Until recently, the combination of cisplatin and 5-fluorouracil (5-FU) was the most common treatment regimen.  Recently, docetaxel (Taxotere) was approved for the treatment of HNC.   Research on the integration of EGFR inhibitors with chemotherapy is now underway at CORT. 

CORT is conducting a phase II study of chemotherapy (Platinol and Taxotere) with or without Vectibix in patients with locally recurrent or metastatic HNC.  The study is a cross-over design.  Patients who do not initially receive Vectibix will be able to receive it if they progress with initial therapy. 

CORT is also participating in the SWOG S0618 study for recurrent or metastatic HNC patients, a phase II  evaluation of E7389, Eribulin.  This drug is a new chemotherapy drug that blocks cell division.  The risks of treatment are fatigue, nausea, vomiting, sensory neuropathy, and low blood counts. 

For more information on these studies, visit http://www.CORTPA.com, or speak with a Study Coordinator at 972-566-5588.

FDA Approves Docetaxel (Taxotere) for Induction Chemotherapy in Head & Neck Cancer

October 1, 2007

On September 28, 2007, the U. S. Food and Drug Administration (FDA) approved docetaxel (Taxotere® Injection Concentrate, Sanofi-Aventis) for use in combination with cisplatin and fluorouracil (5-FU) for the induction treatment of patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).

The safety and efficacy of Taxotere® for the above indication were evaluated in a multi-center, open-label, randomized trial.  In this study, 501 patients with previously untreated locally advanced SCCHN, and performance status 0 or 1, received either Taxotere® 75 mg/m2  followed by cisplatin 100 mg/m2 on day 1, followed by 5-FU 1000 mg/m2/day as a continuous infusion on days 1-4 (TPF regimen) or cisplatin 100 mg/m2 on day 1, followed by 5-FU 1000 mg/m2 /day as a continuous infusion on days 1-5 (PF regimen).  These regimens were administered every 3 weeks for 3 cycles.  All patients in both treatment arms who did not have progressive disease following induction chemotherapy received 7 weeks of chemoradiotherapy (CRT).  During radiotherapy, carboplatin (AUC 1.5) was administered weekly as a 1-hour infusion for a maximum of 7 doses.  Surgery could be considered at anytime following completion of CRT.

Overall survival was significantly prolonged with the Taxotere®-containing regimen (TPF) compared to the PF regimen (log‑rank test, p=0.0058).  The median survival was 70.6 months in the TPF group compared to 30.1 months in the PF group (hazard ratio = 0.70, 95% confidence interval:  0.54, 0.90).

The most frequent adverse events (>40%, any grade) on the TPF arm were neutropenia, anemia, nausea, alopecia, stomatitis, lethargy, vomiting, diarrhea, and anorexia. Neutropenic fever with or without infection occurred in greater than 5% of patients on the TPF arm. Grade 3 or 4 adverse events with a greater than 5% frequency in patients on the TPF arm were neutropenia, infection, stomatitis, nausea, esophagitis/dysphagia/odynophagia, anorexia, vomiting, and anemia. Neutropenia, alopecia, diarrhea, and anorexia were more frequently seen in the TPF arm.

Full prescribing information, including clinical trial information, safety, dosing, drug-drug interactions and contraindications is available at www.fda.gov/cder/foi/label/2007/020449s045lbl.pdf.