Cisplatin plus capecitabine as first-line chemotherapy for recurrent or metastatic head and neck squamous cell cancer: experience outside of a trial setting.

PURPOSE: Cisplatin/5-fluorouracil (5-FU) is an accepted palliative chemotherapy treatment for head and neck squamous cell carcinoma, improving quality of life but not overall survival. Capecitabine in place of 5-FU removes the morbidity of an infusional regime with potential benefit in patient well-being. This study looks at outcomes for cisplatin plus capecitabine (PX) outside of a trial setting. METHODS: Consecutive patients receiving this treatment in a single centre were retrospectively analysed. Cisplatin (mean dose 75 mg/m²) was given on day 1 of a 3-week cycle and capecitabine (mean dose 808 mg/m² twice daily) on days 1-14, for up to 6 cycles. RESULTS: Sixty-five patients (median age 58.6 years) received a median of 4 cycles of chemotherapy. The overall response rate was 30.7%, with a median overall survival of 7.3 months. Treatment was well tolerated with a 10.7% grade 3 and a 1.5% grade 4 neutropenia rate, with no other grade 4 toxicities. One patient died of neutropenic sepsis whilst on treatment. Twenty-seven percent of patients stopped treatment early due to chemotherapy-related side effects. CONCLUSION: PX is well tolerated outside the trial setting with outcomes similar to historical published literature. Ease of administration and benefit to patient convenience make it an attractive alternative to standard palliative treatment.

Synchronous chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck using capecitabine: a single-centre, open-label, single-group phase II study.

AIM: To evaluate the efficacy of concurrent oral capecitabine with accelerated hypofractionated radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Between 2001 and 2004, 50 patients with stage III/IV SCCHN (0 to 2 performance status) were enrolled into this study. The capecitabine dose was between 450 and 550 mg/m(2) twice daily, continuously for 28 days. The radiotherapy dose was 5500 cGy in 20 fractions over 4 weeks. No intensity-modulated radiation was used. We evaluated the complete response rate, toxicity, locoregional control, overall survival, disease-free survival and cancer-specific survival. RESULTS: The median age was 55 (range 38-76) years; 72% had stage IV disease. The median follow-up was 6 years on the 30 surviving patients. Eighty-two per cent of patients completed the course of capecitabine and 94% completed prescribed radiotherapy. There were no treatment-related deaths, grade 3/4 haematological or renal toxicity. Five patients developed drug-related grade 3/4 acute toxicity (cardiac, skin, bowel); 47 developed grade 3/4 mucositis from chemoradiotherapy. Twenty-two (44%) patients required tube feeding and the tube dependency rate at 1 year was 6%. The complete response rate at 3 months was 90% (45/50 patients). Relapse occurred in 17/50 (34%) patients by 5 years. The locoregional control, overall survival, cancer-specific survival and disease-free survival rates at 3 years were 78, 72, 82 and 62%, respectively, and at 5 years were 72, 64, 75 and 56%, respectively. CONCLUSION: This schedule of synchronous capecitabine for locally advanced SCCHN is well tolerated. The local control in this series compares favourably with other synchronous chemoradiotherapy reports. Chronic dysphagia and tube dependence is uncommon with this approach. Capecitabine as targeted therapy given with each fraction of radiotherapy and administered orally may have significant advantages over intravenous, 3 weekly cisplatin.

Can synchronous chemotherapy be added to accelerated hypofractionated radiotherapy in patients with base of tongue cancer?

AIM: To evaluate the tolerability of synchronous chemotherapy and accelerated hypofractionated radiotherapy in patients with locally advanced squamous cell carcinoma of the base of the tongue. MATERIALS AND METHODS: Between 1999 and 2004, 43 patients with stage II-IV squamous cell carcinoma of the base of the tongue were treated with a combined modality of radiotherapy (prescribed 55 Gy in 20 fractions), synchronous chemotherapy and in some cases surgical neck dissection. End points were acute and late toxicity, 3 year locoregional control, overall survival, cancer-specific survival and compliance. RESULTS: The median follow-up for surviving patients was 3.9 years. All patients completed radiotherapy and 30% received neoadjuvant chemotherapy. The median time for the completion of treatment was 27 days (range 25-36). Overall, only 42% completed the prescribed synchronous chemotherapy. However, compliance increased to 60% in patients who did not receive neoadjuvant chemotherapy. Grade 3 mucositis developed in 90% of patients. Prolonged grade 3 mucositis (>4 weeks) was seen in 24/43 (56%) and none developed grade 4 mucositis. There were no toxic deaths. Feeding tube dependency at 1 year was 14%. The 3 year locoregional control, overall survival and cancer-specific survival were 70, 60 and 60%, respectively. Clinical T staging was most significantly associated with poor overall survival, cancer-specific survival and local control. Distant metastases occurred in 6/43 patients (14%), 5/6 without locoregional recurrence. CONCLUSION: The addition of synchronous chemotherapy to accelerated hypofractionated radiotherapy consistently led to grade 3 mucositis. Tumour control rates compare well with published outcomes. Higher mucosal toxicity and lower synchronous chemotherapy compliance compared with other series may suggest that this approach is at the limit of patient tolerability. However, the tumour site investigated and the choice of synchronous chemotherapy agent may also be important. Compliance may be improved using intensity-modulated radiotherapy and agents that do not enhance mucosal toxicity. Longer fractionation will probably increase compliance with chemotherapy, particularly when induction is used before synchronous treatment.

Quality of life measurement in the head and neck cancer radiotherapy clinic: is it feasible and worthwhile?

Quality of Life (QOL) is now a standard end-point in clinical trials. The aim of this non-cohort study was to assess the practical issues surrounding the collection of QOL data in a non-trial setting, and to determine whether it is feasible and worthwhile. Ninety-two patients attending clinics before, or at least 3 months after radiotherapy for head and neck cancer were asked to complete the University of Washington QOL questionnaire (Version 4) and the Hospital Anxiety and Depression Scale. The three most important QOL domains cited by patients after radiotherapy related to saliva production, swallowing and taste. Most patients were able to complete both questionnaires in less than 10 min and reported little difficulty in understanding and completing them. The questionnaires indicated possible clinically significant levels of anxiety and depression in 31% and 16%, respectively. We perceived several benefits of routine QOL data collection in the clinic and this has now been adopted in our own practice.

Tuberculosis screening and compliance with return for skin test reading among active drug users.

OBJECTIVES: This study assessed the independent and combined effects of different levels of monetary incentives and a theory-based educational intervention on return for tuberculosis (TB) skin test reading in a sample of active injection drug and crack cocaine users. Prevalence of TB infection in this sample was also determined. METHODS: Active or recent drug users (n = 1004), recruited via street outreach techniques, were skin tested for TB. They were randomly assigned to 1 of 2 levels of monetary incentive ($5 and $10) provided at return for skin test reading, alone or in combination with a brief motivational education session. RESULTS: More than 90% of those who received $10 returned for skin test reading, in comparison with 85% of those who received $5 and 33% of those who received no monetary incentive. The education session had no impact on return for skin test reading. The prevalence of a positive tuberculin test was 18.3%. CONCLUSIONS: Monetary incentives dramatically increase the return rate for TB skin test reading among drug users who are at high risk of TB infection.