Low-dose, single-agent temsirolimus for relapsed mantle cell lymphoma: a phase 2 trial in the North Central Cancer Treatment Group.

Abstract

BACKGROUND:

The objective of this study was to test a low dose of (25 mg weekly) of the mammalian target of rapamycin kinase inhibitor temsirolimus for patients with relapsed mantle cell lymphoma (MCL).

METHODS:

Patients with relapsed or refractory MCL were eligible to receive temsirolimus 25 mg intravenously every week as a single agent. Patients who had a tumor response after 6 cycles were eligible to continue drug for a total of 12 cycles or 2 cycles after complete remission and then were observed without maintenance.

RESULTS:

Of 29 enrolled patients, 28 were evaluable for toxicity, and 27 were evaluable for efficacy. The median age was 69 years (range, 51-85 years), 86% of patients had stage IV disease, and 71% had > or = 2 extranodal sites. Patients had received a median of 4 prior therapies (range, 1-9 prior therapies), and 50% were refractory to the last treatment. The overall confirmed response rate was 41% (11 of 27 patients; 90% confidence interval [CI], 22%-61%) with 1 complete response (3.7%) and 10 partial responses (37%). The median time to progression in all eligible patients was 6 months (95% CI, 3-11 months), and the median duration of response for the 11 responders was 6 months (range, 1-26 months). Hematologic toxicities were the most common, with 50% (14 of 28 patients) grade 3 and 4% (1 of 28 patients) grade 4 toxicities observed. Thrombocytopenia was the most frequent cause of dose reduction.

CONCLUSIONS:

Single-agent temsirolimus at a dose of 25 mg weekly is an effective new agent for the treatment of MCL. The 25-mg dose level retained the antitumor activity of the 250-mg dose with less myelosuppression. Further studies of temsirolimus in combination with other active drugs for MCL and other lymphoid malignancies are warranted.

• Authors: Stephen M Ansell, David J Inwards, Kendrith M Rowland Jr, Patrick J Flynn, Roscoe F Morton, Dennis F Moore Jr, Scott H Kaufmann, Irene Ghobrial, Paul J Kurtin, Matthew Maurer, Christine Allmer, Thomas E Witzig
• Journal: Cancer (Cancer) Vol. 113 Issue 3 Pg. 508-14 (Aug 01 2008) ISSN: 0008-543X [Print] United States
• PMID: 18543327 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: (c) 2008 American Cancer Society

Chemical References

• Antineoplastic Agents
• temsirolimus
• Sirolimus

Topics

• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Drug Administration Routes
• Drug Administration Schedule
• Female
• Humans
• Lymphoma, Mantle-Cell (drug therapy, mortality)
• Male
• Middle Aged
• Recurrence
• Sirolimus (administration & dosage, adverse effects, analogs & derivatives)
• Survival Analysis
• Treatment Outcome
• United States