Multicenter phase I-II trial of docetaxel, cisplatin, and fluorouracil induction chemotherapy for patients with locally advanced squamous cell cancer of the head and neck.

PURPOSE: We conducted a phase I-II, multi-institutional trial to determine the maximum-tolerated dose (MTD) of cisplatin in an induction chemotherapy regimen of docetaxel, cisplatin, and fluorouracil for squamous cell cancer of the head and neck (SCCHN) and to determine the safety, tolerability, and efficacy of the regimen at MTD. PATIENTS AND METHODS: A total of 43 patients with previously untreated, locally advanced, curable SCCHN were entered. Overall, 29 patients (67%) had N2 or N3 nodal disease and nine (21%) had T4 primary tumors. All patients received docetaxel 75 mg/m(2) on day 1; cisplatin at 75 (level I) or 100 (level II) mg/m(2) on day 1; and a continuous fluorouracil infusion at 1,000 mg/m(2)/d on days 1 through 4. Patients were treated with prophylactic antibiotics on days 5 through 15. Cycles were repeated every 21 days for a total of three cycles. Patients then received definitive therapy based on institutional preferences. RESULTS: Thirteen patients were treated at level I, and 30 patients were treated at level II. All 43 patients were assessable for toxicity. There were no major differences in toxicity between level I and level II. Cisplatin-associated grade 3 or 4 hypomagnesemia or hypocalcemia occurred in 13 (30%) and hearing loss in two patients (5%). Grade 3 or 4 neutropenia was observed in 41 patients (95%) and febrile neutropenia occurred in eight (19%). There was one serious infection (2%). There were 17 (40% [95% confidence interval [CI], 25% to 56%]) clinical complete responders (CR), 23 (54% [95% CI, 39% to 69%]) partial responders (PR), one (2%) with no change, and two (5%) unassessable patients. Major responses (CR, PR) were observed in 40 (93% [95% CI, 81% to 99%]) patients. Primary site CR was documented in 24 (54%) of patients. Postchemotherapy primary site biopsies were performed in 25 patients (58%) and pathologically negative biopsy was obtained in 11 (92%) of 12 primary site clinical CRs and seven (54%) of 13 with PR or no change. Overall, negative biopsies were obtained in 18 patients (72%). CONCLUSION: TPF induction chemotherapy can be delivered safely with a cisplatin dose of 100 mg/m(2) in previously untreated patients with SCCHN. The regimen is associated with a high rate of primary site clinical and pathologic CRs. Phase III comparison with cisplatinum and fluorouracil chemotherapy is warranted.

Coexisting myelodysplasia and myeloproliferative features in a single clone containing 5q-, Ph and i(17q).

A case with myelodysplasia in which a single clone contained both 5q- and Ph chromosomes at diagnosis is presented. The patient subsequently developed leukocytosis and at that time was found to have acquired an additional chromosomal abnormality, i(17)(q10). This case illustrates the role of three different genetic changes that impart different clinical characteristics, i.e. myelodysplastic as well as myeloproliferative changes, as part of a multistep leukemogenic process.

Chemoprevention of colorectal cancer: dietary and pharmacologic approaches.

Colorectal cancer is a major cause of death in the United States, where it accounts for approximately 57,000 deaths per year. Thus, the prevention of this disease would have a significant impact on public health. Chemoprevention is defined as the use of natural or pharmacologic agents to disrupt the process of carcinogenesis. Substances explored as chemopreventive agents in colorectal cancer include: (1) the nonsteroidal anti-inflammatory drugs (NSAIDS), which may inhibit the evolution and formation of adenomas by their inhibition of cyclooxygenase and decrease of prostaglandin synthesis; (2) antioxidants, such as vitamin E or C, which may modulate carcinogenic substances; and (3) folate and calcium, which may interfere with tumor cell growth and replication. Dietary intervention can be accomplished by decreasing fat intake and increasing fiber consumption, both of which have been linked to a lower incidence of colon cancer in multiple epidemiologic studies. This field is continuing to evolve. Hopefully, ongoing research efforts will offer a better understanding of the role of these and other substances in chemoprevention. This article summarizes the available data regarding dietary and pharmacologic approaches to colorectal cancer chemoprevention.