Troxacitabine. a promising new L-nucleoside, inhibits DNA polymerase and leads to complete DNA chain termination. The National Cancer Institute of Canada Clinical Trials Group (NCIC-CTG) conducted a phase II study to assess the efficacy and toxicity of troxacitabine in untreated patients with advanced non-small-cell lung cancer (NSCLC). Previously untreated patients were eligible if they had inoperable stage IIIB or IV NSCLC, ECOG PS < or = 2, adequate hematology and biochemistry, and at least one bidimensionally measurable lesion. Patients with prior malignancy or brain metastases were excluded. Troxacitabine (10 mg/m(2)) was administered intravenously over 30 minutes every 3 weeks. Between June 1999 and May 2000, 17 eligible patients received treatment. Patient characteristics included: median age 64 years; female 41%; stage IV (94%); PS 0 (12%), 1 (59%), and 2 (29 %), 3 or more disease sites (59%). In 17 patients, there were 8 stable disease, 9 disease progression, and no objective responses. Median duration of stable disease was 3.6 months (range = 2.0-7.1). A total of 56 cycles were administered (median = 3), and 88% of patients received 90% or more of the planned dose intensity. The majority (82%) of patients experienced skin rash. Hematologic and biochemical toxicities, grade 3/4 (%) were: granulocytopenia (41), anemia (12), thrombocytopenia (6), and hyperglycemia (6). Troxacitabine appears to have little activity in NSCLC in the dose and schedule tested.

Aged↗

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Role of leucovorin dosing and administration schedule.

Leucovorin (LV) is commonly administered in association with 5-fluorouracil (5-FU) to enhance its cytotoxic effects. In this paper, the cellular and clinical pharmacology of 5-FU potentiation by LV are reviewed, and the dosing and administration schedules are discussed in relation to reported clinical trials. In vitro experimental data suggest that prolonged cellular exposures to relatively low LV concentrations simultaneously with prolonged 5-FU administration are the optimal conditions to enhance 5-FU efficacy. Clinical studies of 5-FU/LV in metastatic colorectal carcinoma have established that 5-day bolus 5-FU with low-dose bolus LV injections yield therapeutic benefits equivalent to those obtained with intravenous bolus schedules using higher doses of LV. It remains to be determined, however, if bolus administration schedules are the optimal clinical treatment regimens. Infusional 5-FU/LV regimens appear to be a strategy worthy of further clinical investigation.

Antidotes↗

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[Retinal tear appearing after photocoagulation. Apropos of a case].

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Eye Diseases↗

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Tamoxifen-induced tumor stimulation and withdrawal response.

A postmenopausal breast cancer patient with a measurable lung metastasis was treated with tamoxifen. The tumor doubling time of the pulmonary lesion was 140 days during spontaneous growth and 52 days during tamoxifen therapy, an almost threefold increase in tumor growth rate. This stimulation persisted fro 1 month after discontinuation of tamoxifen and was followed thereafter by a withdrawal regression lasting greater than 6 months. Awareness of the possible tumor growth enhancement with tamoxifen is of importance especially in view of its prolonged activity. Hormone withdrawal regression may occur following tamoxifen therapy, and a sufficient time interval should therefore elapse between cessation of tamoxifen and initiation of other therapeutic modalities.

Breast Neoplasms↗