ognosis Despite advances in systemic COX Inhibitors therapies, the median overall survival for patients with recurrent or metastatic head and neck squamous cell carcinoma remains less than 1 year. The prognosis of locally advanced HPV positive HNSCC is significantlybut bone marrow suppression is mild, except in patients with dihydropyrimidine dehydrogenase deficiency. Some oncologists have argued that the standard 14 days on and 7 days off dosing schemes suggested by the Physician,s Desk Reference and the Xeloda package insert may not be the optimal way for capecitabine delivery nor for dose adjustments, particularly since there is much interpatient variability in the blood levels of 5 FU.
Such interpatient variability encourages flexibility in exploring schedules of capecitabine that may best avoid unpredictable toxicities while using dose adjustments in terms of limiting days of exposure than dose reductions that run the risk of leading to daily subtherapeutic 5 FU levels. The combination of cisplatin and continuous daily doses of 5 FU or by bolus has been the backbone of chemotherapy regimens for various types of cancer, such as head and neck, esophageal and gastric. The well known toxicities of cisplatin include nausea, vomiting, myelosuppression, renal, neurosensory and auditory dysfunction. In combination with capecitabine, major concerns would be interference with oral tolerance, and also compounding of renal dysfunction. With these concerns in mind we proposed a phase I study by employing escalating variable duration of treatment with capecitabine in combination with a modest dose of cisplatin every 3 weeks.
Once the maximum tolerated dose was obtained, we expanded the level at the recommended phase two dose to test tolerance with repeated administration in patients with upper gastrointestinal cancer. Capecitabine maintenance was provided by Roche Laboratories for patients who completed six cycles of this combined treatment or those who underwent resection following neoadjuvant treatment with the combination of cisplatin and capecitabine. Patients and Methods Eligibility. Eligible patients who were enrolled were treated at the Tisch University Hospital, NYU Clinical Cancer Center, Bellevue Hospital Center and the Manhattan VA Hospital Center, after histologically confirmed locally advanced or metastatic cancer of the upper gastrointestinal tract, head and neck, lung, breast, or cancer of unknown primary.
Each patient had Eastern Cooperative Oncology Group Performance Status of 2 or better, adequate hematological, renal and liver function were required within 2 weeks of the start of drug administration: absolute neutrophil count 1,500/l, platelet count 100,000/l, BUN 30 mg/dl, calculated creatinine clearance 60 ml/min, total bilirubin 2 mg/dl, aspartate aminotransferase 3 times the upper limit of normal, and alkaline phosphatase 3 times the upper limit of normal. For patients who received prior treatment, at least 6 months had to have elapse since the last infusional 5 FU or cisplatin therapy, and at least 3 weeks since the last radiation therapy or any chemotherapy other than 5 FU/cisplatin. A patient was considered evaluable for response upon completion of two cycles and had clinical and radiographic assessments, they were reassessed every two cy