Faculty Bibliography

Between January 1975 and December 1980, 111 patients with AJCC stages III and IV squamous cell carcinoma of the head and neck were treated with surgery followed by planned postoperative radiation therapy. A previous analysis of a subgroup of these patients showed that, when radiation was delayed more than 6 weeks from surgery, a higher incidence of regional failure occurred compared with the incidence observed when therapy began within a 6 week period. We have looked back at this group of patients plus others in an attempt to determine whether other factors played a role in the results obtained. In the current study, 50 patients had a delay of 6 weeks or more and, of these, 11 (22%) suffered a locoregional recurrence. However, 8 of these 11 patients received suboptimal radiation doses (less than 56 Gy) for permanent control of the disease. In fact, of 17 patients who received at least 60 Gy and had more than a 6 week delay, only 2 (12%) had locoregional failure. This was similar to the incidence of failure in the patients who received at least 60 Gy and who started radiation within the first 6 weeks from surgery (3/20 [15%]). The effect of delay was apparent only in those who received less than 60 Gy (27% vs. 7%, P less than 0.05). Therefore, we cannot validate the previous conclusion that a greater than 6 week delay in the delivery of postoperative radiation therapy in advanced head and neck cancers produces poorer results. The current analysis suggests that a prolonged delay in postoperative radiation therapy in itself does not have a negative impact on locoregional control as long as appropriate tumorcidal doses of more than 60 Gy are employed

Taxol is a unique plant product that promotes in vitro assembly of microtubules. In a phase I trial, adults with advanced solid tumors were given taxol (formulated with cremophor EL and dehydrated alcohol) as a 3-hour iv infusion every 21 days. The total dose administered ranged from 15 to 230 mg/m2 in nine escalation steps. Leukopenia, thrombocytopenia, nausea and vomiting, alopecia, stomatitis, transient rashes, increases in serum triglyceride levels, and hypersensitivity reactions were observed. Hypersensitivity reactions characterized by acute dyspnea, generalized erythema, and hypotension immediately following the initiation of the taxol infusion occurred in three of five patients receiving greater than or equal to 190 mg/m2 (18% of patients overall). No antitumor activity was observed. Hypersensitivity reactions constituted a treatment-limiting toxicity for this preparation of taxol given on this schedule over the dosage range examined. With the severity and unpredictability of the hypersensitivity reactions, further usage of taxol is not indicated with this drug formulation on this administration schedule. Further studies are warranted to uncover ways to permit the safe administration of taxol

Taxol increases the rate and extent of microtubule assembly in vitro and stabilizes microtubules in vitro and in cells [Schiff, P. B., Fant, J., & Horwitz, S. B. (1979) Nature (London) 277, 665-667; Schiff, P. B., & Horwitz, S. B. (1980) Proc. Natl. Acad. Sci. U.S.A. 77, 1561-1565]. We report herein that taxol has the ability to promote microtubule assembly in the absence of microtubule-associated proteins, rings, and added guanosine 5'-triphosphate (GTP or organic buffer. The drug enhances additional microtubule assembly when added to microtubules at apparent steady state. This additional assembly can be attributed to both elongation of existing microtubules and spontaneous nucleation of new microtubules. Taxol-treated microtubules have depressed dissociation reactions as determined by dilution experiments. The drug does not inhibit the binding of GTP or the hydrolysis of GTP or guanosine 5'-diphosphate (GDP) in our microtubule protein preparations. Taxol does not competitively inhibit the binding of colchicine to tubulin

Taxol, an experimental antitumor agent and stabilizer of microtubules, inhibits in vitro replication of the human pathogenic hemoflagellate Trypanosoma cruzi. Micromolar concentrations of the drug prevent the completion of cell division in these organisms but allow the multiplication of cell organelles such as the nucleus, kinetoplast, and flagellum. The result is the formation of motile organisms that have extra organelles but cannot fully replicate. Division proceeds to a relatively fixed locus on the long axis of the organism, suggesting the presence of a specific affected structure or function at this site. It is postulated that taxol produces these effects by stabilizing a portion of the microtubular cytoskeleton of T. cruzi