Our objective was to determine the maximum tolerated dose (MTD) of two administration sequences of docetaxel and gemcitabine in cancer patients, and to describe the pharmacokinetics of both drugs. Patients were treated in a 4-weekly schedule at two dose levels: gemcitabine 800 mg/m2 on days 1, 8 and 15, and docetaxel 85 or 100 mg/m2 on day 15 (levels I and II). The protocol was amended to a 3-weekly schedule, testing gemcitabine 800 or 1000 mg/m2 on days 1 and 8, with docetaxel 85 mg/m2 on day 8 given initially (dose levels IIIa and IV). At the recommended dose, an extra cohort of patients initially received gemcitabine (dose level IIIb). Eleven patients were treated with the 4-week schedule; 29% of cycles were delayed predominantly because of hematological toxicity. Four patients developed dose-limiting toxicities (DLTs), predominantly hematological. In the 3-week schedule, 14 patients were treated. At level IV, three of four patients developed DLTs, defining the MTD. With the reverse sequence, three patients received a total of 10 cycles. Overall, nine partial remissions were observed. We conclude the recommended dose for phase II studies is gemcitabine 800 mg/m2 on days 1 and 8, combined with docetaxel 85 mg/m2 on day 8, on a 3-weekly schedule. Gemcitabine distribution is significantly altered upon docetaxel administration.

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Although XR5000 was generally well tolerated, these results do not support further evaluation in patients with glioblastoma multiforme using this dose and schedule.

Hypoplastic acute leukemia (HAL) is characterized by pancytopenia and by hypocellularity of the bone marrow. The marrow contains equal to or more than 30% myeloblasts. Absence of tissue infiltrates and/or tumor masses is mandatory. Eight patients are described here. They do not fit into the FAB classification for either acute nonlymphocytic leukemia (ANLL) or myelodysplastic syndrome (MDS), except for one patient who subsequently proved to have a chronic myelomonocytic leukemia (CMML). The median age is 65 years. Two patients, including the CMML patient, are alive, 22 and 6 months from diagnosis. Six patients have died. The median survival is 8 months. Normal bone marrow cells cultured either with HAL sera or with HAL peripheral blood mononuclear cells as feeders and exogenous GM-CSF yielded subnormal CFU-GM counts. This might indicate inhibitory activity of HAL serum and defective stimulatory activity of HAL peripheral blood mononuclear cells.

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