There was a reasonably high rate of PR associated with concurrent neoadjuvant chemotherapy and RT, and a high percentage of patients who ultimately were rendered completely disease-free. However, treatment-related morbidity and mortality was common. Median survival seemed to be only modestly improved beyond that achieved with less intensive means of treatment. However, a group has emerged of patients who enjoy prolonged disease-free survival and possible cure.

The MTD of paclitaxel using a weekly schedule is 175 mg/m2/wk for 6 of 8 weeks. Neutropenia limits dosing acutely, but neuropathy is limiting with sustained therapy. This schedule of paclitaxel results in a twofold to threefold increase in dose-intensity with less toxicity than anticipated from conventional dosing. Further evaluation of this schedule is warranted to assess efficacy and toxicity of prolonged administration.

Esophagitis is the principle dose-limiting toxicity of weekly paclitaxel and thoracic radiation in the outpatient setting. A phase II trial using concurrent radiation and paclitaxel at the MTD of 60 mg/m2/wk is underway.

In 19 dogs, the release of autologous venous thrombi to the lungs resulted in bronchoconstriction, with a rapid rise in the total lung resistance and a fall in the lung compliance. The respiratory rate and arterial-alveolar CO2 tension difference also increased significantly. The administration of either heparin or a 5-HT antagonist completely prevented the bronchoconstriction, without affecting either the respiratory rate or arterial-alveolar CO2 tension difference. Bronchoconstriction resulting from direct 5-HT infusion was not prevented by heparin, nor was the contraction of an isolated rat uterus in response to 5-HT. However, 5-HT was not released from canine platelets by thrombin in vitro, in the presence of heparin. The evidence suggests that bronchoconstriction in the dog due to autologous pulmonary emboli results from thrombin-induced 5-HT release, and that heparin, by its antithrombin action, prevents this release.