A phase I study of gemcitabine combined with vinblastine in patients with solid tumors

Gemcitabine and vinblastine are chemotherapeutic drugs with a wide spectrum of antitumor activity. We conducted a phase I trial to define the maximal tolerated dose of this combination.

Twenty-nine patients with a variety of solid tumors with measurable disease were included. Twenty-seven of these patients had been previously treated with chemotherapy. The use of hematological growth factors was not allowed. The maximal tolerated dose was defined as the level in which WHO grades 3 or 4 non-hematological toxicity would occur in at least a third of the patients.

The maximal tolerated dose was reached at level 5, which consisted of gemcitabine (1000 mg/m2) with vinblastine (3 mg/m2) given intravenously on days 1, 8 and 15 every 28 days. At this level, one patient had WHO grade 3 cerebellar toxicity and another WHO grade 4 anorexia. Furthermore, patients were able to receive all 3 weekly doses of chemotherapy in only 2 out of 10 cycles of treatment given at this level. We also observed 5 episodes of WHO grades 1 and 2 neuropathy, most of which (4/5) occurred in patients previously exposed to neurotoxic chemotherapy. We recorded 2 partial responses (one at level 3 and the other at level 4) and 8 instances of stable disease after 3 scheduled cycles of the combination.

We therefore recommend gemcitabine (1100 mg/m2) plus vinblastine (5.5 mg/m2) given on days 1 and 8 every 21 days (level 4) for previously treated patients with solid tumors, with special caution in patients previously exposed to neurotoxic chemotherapy.