Seminars in oncology
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Seminars in oncology · Dec 1997
ReviewTreatment of patients with upper gastrointestinal carcinomas.
Carcinomas of the stomach and esophagus are a major health problem worldwide. Cancer remains incurable when it is metastatic or unresectable, and new active agents are needed to improve the outcome for these patients. Three phase II studies of paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) are described here. ⋯ Toxicity with this combination has been moderate, and there have been no treatment-related deaths. With the reduced starting dose of 5-fluorouracil, the tolerance of this combination has improved substantially both in the inpatient and outpatient settings, resulting in a low frequency of grade 3 or 4 nonhematologic toxicity. Response has been higher in patients with squamous cell carcinoma.
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Seminars in oncology · Dec 1997
ReviewStereotactic radiosurgery and radiotherapy: new developments and new directions.
Stereotactic irradiation is a precise method for the delivery of focused radiation beams to small intracranial targets. Treatment can be administered in single or multiple fractions (radiosurgery or stereotactic radiotherapy, respectively). The technology has evolved rapidly because of advances in both hardware and software design. Clinical indications are unfolding through the prospective trial mechanism.
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Seminars in oncology · Dec 1997
Intravenous prophylaxis for paclitaxel-related hypersensitivity reactions.
Severe hypersensitivity reactions to paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) were reported during early phase I trials. A premedication regimen consisting of oral steroids 12 and 6 hours before treatment with paclitaxel as well as immediate infusion of diphenhydramine and cimetidine (or ranitidine) before paclitaxel markedly decreased the incidence of hypersensitivity reactions. ⋯ In both these trials, all premedication for hypersensitivity reactions was administered intravenously immediately before paclitaxel. No significant hypersensitivity reactions were reported in these two trials, and, subsequently, a large retrospective search of a computerized pharmacy database concluded that a single-dose regimen of intravenous dexamethasone, diphenhydramine, and cimetidine is a safe and convenient alternative for prevention of hypersensitivity reactions associated with outpatient paclitaxel administration.
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Seminars in oncology · Dec 1997
Clinical TrialConcurrent paclitaxel, carboplatin, and radiotherapy in advanced head and neck cancers: a phase II study--preliminary results.
Radiotherapy or surgery alone for advanced head and neck cancer generally yields poor results. Paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) and carboplatin have both shown excellent radiosensitization through two discrete mechanisms, namely, blocking the cell cycle in the G2/M phase and inhibiting DNA repair. In an effort to improve locoregional control and survival, a prospective phase II study was initiated using paclitaxel 60 mg/ml and carboplatin (area under the concentration-time curve of 1), each given as a single dose weekly with concurrent conventional fractionated external beam radiotherapy. ⋯ Concomitant paclitaxel, carboplatin, and external beam radiotherapy yielded excellent clinical responses, but produced significant grade 3/4 toxicity. In the operable group, the majority of responders had a complete pathologic response. These preliminary findings will be assessed in terms of response duration, organ preservation, and long-term survival.
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Seminars in oncology · Dec 1997
Clinical TrialA phase I trial of radiotherapy and simultaneous 24-hour paclitaxel in patients with locally advanced head and neck squamous cell carcinoma.
Preclinical studies have demonstrated that tumor cells exposed to paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) for protracted periods (ie, 24 hours) and then irradiated undergo enhanced radiation-induced cell kill. Importantly, paclitaxel-induced tumor cell mitotic arrest at the time of radiation was associated with the enhanced cell kill. At the Case Western Reserve Cancer Center, we have conducted a phase I trial in 24 patients with either locally advanced or recurrent/metastatic head and neck squamous cell carcinoma to evaluate the clinical and pharmacologic effects of a 24-hour paclitaxel infusion combined with radiotherapy. ⋯ Pharmacokinetic studies revealed that a dose of > or =75 mg/m2 achieved near steady-state mean paclitaxel plasma concentrations greatly exceeding the threshold concentrations shown to alter microtubule function and induce tumor cell mitotic arrest in vitro. Pharmacodynamic studies performed at 21 to 26 hours after initiation of infusion demonstrated that a dose of > or =75 mg/m2 uniformly induced tumor cell mitotic arrest and oral epithelial mitotic arrest. The pharmacologic data and outcome results provide a strong rationale for the continued use of a 24-hour paclitaxel infusion and concurrent radiation for the treatment of newly diagnosed, locally advanced head and neck squamous cell carcinoma in an experimental setting.