Phase II trial of sorafenib in patients with recurrent or metastatic squamous cell carcinoma of the head and neck or nasopharyngeal carcinoma.

PURPOSE: To determine the efficacy and safety of single-agent sorafenib in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck (SCCHN) and nasopharyngeal carcinoma (NPC). PATIENTS AND METHODS: In this single-arm phase II trial, oral continuous sorafenib was administered in 28-day cycles. Patients had

Phase I/II trial of erlotinib and cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: a Princess Margaret Hospital phase II consortium and National Cancer Institute of Canada Clinical Trials Group Study.

PURPOSE: To determine the phase II dose and objective response rate of erlotinib, a selective epidermal growth factor receptor tyrosine kinase inhibitor, in combination with cisplatin in patients with recurrent or metastatic squamous cell carcinoma of the head and neck (HNSCC). PATIENTS AND METHODS: HNSCC patients with no prior chemotherapy and measurable disease were treated in three escalating-dose cohorts of daily continuous oral (PO) erlotinib and intermittent intravenous (IV) cisplatin given every 21 days. The recommended phase II dose (RPTD) was then evaluated in a two-stage trial with a primary end point of objective response rate. RESULTS: A total of 51 patients were enrolled. The RPTD was identified as erlotinib 100 mg PO daily and cisplatin 75 mg/m2 IV every 21 days. Forty-five patients were treated at the RPTD, of which 44 and 43 were eligible for toxicity and efficacy evaluations, respectively. The intention-to-treat response rate was 21%, with one complete and eight partial responses (95% CI, 10% to 36%), and disease stabilization was achieved in 21 patients (49%; 95% CI, 33% to 65%). Median progression-free survival was 3.3 months (95% CI, 2.7 to 4.8 months) and median overall survival was 7.9 (95% CI, 5.6 to 9.5) months. The combination was well tolerated, with minimal grade 3 or higher toxicity. Subgroup analysis suggested that patients who developed higher grade skin rashes during cycle 1 had better survival outcomes (P = .034). CONCLUSION: This schedule of erlotinib and cisplatin has a favorable toxicity profile and has antitumor activity in HNSCC comparable to standard combination chemotherapy regimens.

Phase I trial of gemcitabine, doxorubicin and cisplatin (GAP) in patients with advanced solid tumors.

A phase I study was conducted to determine the recommended phase II dose, safety profile and anti-tumor activity of a combination regimen of gemcitabine, doxorubicin and cisplatin (GAP). Gemcitabine (G) and doxorubicin (A) were administered on days 1 and 8 at increasing doses (starting level 800 and 15 mg/m, respectively). Cisplatin (P) was given at a fixed dose of 50 mg/m2 (day 1). Treatment cycles were repeated every 3 weeks. Nineteen patients received 76 cycles of treatment. A and G were escalated up to 20 and 1000 mg/m2, and finally de-escalated to 15 and 800 mg/m2. The dose-limiting toxicity was neutropenic fever that was observed in 21% of the patients. Non-hematological toxicities included mild/moderate nausea, vomiting, diarrhea and fatigue, observed in 58, 37, 21 and 95% of the patients, respectively. Of 19 patients with evaluable disease, six patients had a partial response yielding an overall response rate of 31.6 % (95% confidence interval 12.6-56.6%) by intention-to-treat. We conclude that GAP is an active and tolerable treatment combination, with minimal visceral organ toxicities.

Correlation of Epstein-Barr virus DNA in cell-free plasma, functional imaging and clinical course in locally advanced nasopharyngeal cancer: a pilot study.

BACKGROUND: We evaluated the feasibility of using quantitative real-time polymerase chain reaction (PCR) in monitoring Epstein-Barr virus (EBV) DNA concentrations in cell-free plasma of patients with localized nonmetastatic nasopharyngeal carcinoma (NPC) treated with chemoradiation. METHODS: Cell-free plasma EBV DNA was quantified in six patients with locally advanced, nonmetastatic nasopharyngeal cancer (NPC) who underwent chemoradiation therapy (CRT) and correlated with magnetic resonance imaging (MRI), positron emission tomography (PET) scans, and clinical course. RESULTS: The mean concentration of EBV DNA was 24,610 copies/mL, 682 copies/mL, and 64.5 copies/mL in the pretreatment, posttreatment, and last follow-up samples, respectively. Four of the six patients had normal PET scans and reduction of EBV DNA copy numbers to minimal levels after treatment and, despite equivocal posttreatment MRI scans, are clinically free of recurrent disease. Two of the six patients had elevated EBV DNA copy numbers immediately after treatment, but a metastatic workup was clear at the time; both subsequently relapsed with distant metastases 5 and 11 months later. Although the posttreatment PET scans were abnormal in both of these cases, they were not predictive of the subsequent sites of tumor relapse. CONCLUSIONS: To our knowledge, this is the first report on the correlation between EBV DNA levels and PET scan results in patients with NPC. Reductions in EBV DNA levels and normal PET scans after treatment were consistent among patients who had residual abnormality on MRI images. Persistently elevated EBV DNA levels and abnormal PET scans after treatment suggest residual disease. Further evaluations are required to determine the relative contributions of these two novel techniques in predicting residual disease in locally advanced NPC.

Epstein-Barr virus DNA measured in nasopharyngeal brushings in patients with nasopharyngeal carcinoma: pilot study.

OBJECTIVE: We measured the amount of tumour-derived Epstein-Barr virus (EBV) deoxyribonucleic acid (DNA) in the nasal brushings of nasopharyngeal carcinoma (NPC) patients to determine the correlation with tumour load and response to treatment. MATERIALS AND METHODS: Twenty-eight patients with NPC were included in the study. Baseline measurements of EBV from nasopharyngeal brushings were obtained from 26 patients prior to treatment. A follow-up sample was available from 11 of these patients post-treatment and from 2 additional patients who did not have a baseline sample. Quantitative real-time polymerase chain reaction (PCR) using SYBR Green I fluorescent dye was used to detect the EBV DNA copy number. RESULTS: Nasopharyngeal brush biopsies showed a high copy number of EBV DNA in most of the pretreatment samples (median 9714 copies/mL). The highest copy number detected was 14536944 copies/mL in one sample. In the post-treatment follow-up samples, the copy number was significantly lower (median 6 copies/mL). CONCLUSIONS: We have demonstrated that EBV DNA can be detected in the brush biopsies from NPC patients using quantitative real-time PCR. These pilot data suggest that nasopharyngeal brushings with PCR detection of EBV may be an effective tool for determining local tumour response. The potential of this technique as an NPC tumour marker for post-treatment follow-up is being validated with larger patient numbers.