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Purpose: To determine the maximum-tolerated dose, toxicity profile, and pharmacokinetics of a fixed dose of paclitaxel followed by increasing doses of carboplatin, given weekly to patients with advanced esophageal or gastric junction cancer. Experimental Design: Paclitaxel was administered on day 1 as a 1-h infusion at a fixed dose of 100 mg/m2 followed by a 1-h infusion of carboplatin targeting an area under the curve (AUC) of 2–5 mg × min/ml, with cycles repeated on days 8, 15, 29, 36, and 43. Results: Forty patients [36 males; median (range) age, 57 (40–74) years] were enrolled. Dose-limiting toxicity was observed at a carboplatin AUC of 5 mg × min/ml and consisted of treatment delay attributable to myelosuppression. No grade 3/4 treatment-related nonhematological toxicity was observed. The highest dose intensity (>95% of the planned dose over time) was achieved with a carboplatin AUC of 4 mg × min/ml. The mean (±SD) AUCs of unbound (Cu) and total paclitaxel were 0.662 ± 0.186 and 7.37 ± 1.33 μm × h, respectively. Clearance of Cu was 188 ± 44.6 liter/h/m2, which is not significantly different from historical data (P = 0.52). Cremophor EL clearance was 123 ± 23 ml/h/m2, similar to previous findings. Of 37 patients evaluable for response, 1 had complete response, 19 had partial response, and 10 had stable disease, accounting for an overall response rate of 54%. Conclusions: This regimen is very tolerable and effective, and the recommended doses for additional studies are paclitaxel (100 mg/m2), with carboplatin targeting an AUC of 4 mg × min/ml.

A prospective study was set up to evaluate the influence of psychological distress on the outcome of lumbosacral fusion in a group of chronic low back pain (CLBP) patients. Response to low back surgical procedures depends upon physical and psychological factors. Various reports exist concerning the influence of a patient's psychological condition on the outcome of low back surgery. Few investigators, however, have checked this influence in a prospective manner. A psychogenic back pain score (NPL) was administered to 53 CLBP patients (24 men and 29 women) prior to surgery, to evaluate the presence of psychological distress. According to the test score patients were divided in an "organic", an "uncertain" and a "psychogenic" group. Disability in activities of daily living resulting from the back pain was also scored preoperatively with the Oswestry Disability Index (ODI). Twelve months after surgery the ODI was readministered to the 50 patients available to follow-up. Each group separately showed significant improvement of disability 12 months after fusion, however, the "organic" group scored significantly better than the "psychogenic" group. Questionnaires about back pain, sciatic pain and use of analgesics and Visual Analog Scales regarding pain and disability also indicated better results in the "organic" group. Psychological distress deteriorates the subjective outcome of lumbosacral spine fusion and psychological screening should indeed be an integral part of the global assessment of CLBP patients, especially when surgery is considered.