NEW ORLEANS—2-Chlorodeoxyadenosine (cladribine, 2-CdA [Leustatin]) can produce response rates of 80% and higher in patients with mantle cell lymphoma (MCL), according to two studies presented at the ASH meeting. One study examined 2-CdA as monotherapy, and the other studied it combined with mitoxantrone (Novantrone).
The North Central Cancer Treatment Group (NCCTG) conducted a phase II trial of 2-CdA in 26 patients who had as-yet-untreated MCL. Each patient received 5 mg/m² of intravenous 2-CdA per day for 5 days and then repeated the treatment 28 days later. Patients who had a complete response continued to be observed. Patients who had a partial response received two to four more cycles of 2-CdA, to a maximum of six. Patients whose disease progressed were removed from the study.
Highly Active Single Agent
Patients tolerated 2-CdA well. One person had a grade 4 toxicity (diarrhea), and others had grade 3 and lower toxicities, including rashes. No deaths were due to 2-CdA, although one patient died from progression of MCL, and another died of an unrelated cancer.
Of the 26 patients who started the study, 31% had a complete remission and 50% had a partial remission by NCCTG criteria. Median time to relapse was 16 months. As of November 1999, 9 patients had not relapsed.
2-CdA is “highly active as a single agent for the treatment of mantle cell lymphoma,” concluded David Inwards, MD, of the Mayo Clinic. Although the drug has minimal toxicity, treatment results are limited by the high relapse rate.
Mathias Rummel, MD, of Johann Wolfgang Goethe-University in Frankfurt am Main, Germany, and researchers from several other German clinics investigated the use of 2-CdA combined with mitoxantrone. They chose mitoxantrone as the second agent because it is well tolerated by elderly patients and is synergistic with 2-CdA.
The subjects were 64 people with MCL, immunocytoma, or other low-grade lymphoma. The 43 patients who were newly diagnosed received an intermittent 2-hour infusion of 2-CdA at 5 mg/m² on days 1 through 3 and mitoxantrone at 8 mg/m² as an intravenous bolus on days 1 and 2. The 21 patients who were in their first relapse received the same dose of 2-CdA, but received 12 mg/m² of mitoxantrone on day 1 only. Patients received a maximum of six cycles every 4 weeks.
Overall, 24 (38%) of the patients had a complete response and 32 (50%) had a partial response to the combined therapy. One result that surprised the researchers, given the usual poor response of MCL to treatments, Dr. Rummel reported, was that all 17 patients with MCL responded, with 6 (35%) having a complete response and 11 (65%) having a partial reponse.
Dr. Rummel concluded that the combination of 2-CdA and mitoxantrone was effective in both untreated and previously treated patients with lymphoma. The researchers found that this combined treatment was more toxic than 2-CdA by itself. Seventy percent of the patients had a grade 3 or grade 4 granulocytopenia.
Five patients developed herpes zoster, and two had bacterial pneumonia. Still, the toxicity was low enough to enable the treatment to be administered on an outpatient basis.
In March 1999, the German group started a prospective trial to test the combination of 2-CdA plus mitoxantrone against MCP (mitoxantrone, chlorambucil, prednisone).