Final report of toxicity and efficacy of a phase II study of oral cyclophosphamide, thalidomide, and prednisone for patients with relapsed or refractory multiple myeloma: A Hoosier Oncology Group Trial, HEM01-21.

Thalidomide has direct antimyeloma and immunomodulatory effects. In addition, both thalidomide and metronomic chemotherapy inhibit angiogenesis. The synergy of such a combination may decrease toxicity while maintaining efficacy. The Hoosier Oncology Group conducted a phase II trial of oral cyclophosphamide (50 mg b.i.d. for 21 days), thalidomide (200 mg/day), and prednisone (50 mg q.o.d.) (CTP) per 28-day course in patients with relapsed multiple myeloma (MM). Of the 37 patients enrolled, 16 had prior stem cell transplantation. The median follow-up time was 25.3 months (95% confidence interval [CI] 23.2-27.7). Of 35 patients treated, 22 patients (62.9%) responded: 7 (20.0%) complete responses, 2 (5.7%) near-complete responses, and 13 (37.1%) partial responses. Eight patients (22.9%) had stable disease, and three (8.6%) had disease progression. Two patients withdrew from the study early due to reasons unrelated to progression or toxicity and were treated as nonresponders. The median time to best response and time to progression were 3.6 months (95% CI 2.8-10.9) and 13.2 months (95% CI 9.4-21.0), respectively. The median number of treatment cycles was seven (range 1-12 cycles). Grade III to IV toxicities included leukopenia (42.9%; febrile neutropenia, 11.4%), hyperglycemia (20%), sensory neuropathy (11.4%), thromboses (8%), and motor neuropathy (5.7%). No patient withdrew from the study due to toxicity. The efficacy and low toxicity of the CTP regimen support the future development of such an approach in MM.

Weekly bortezomib/methylprednisolone is effective and well tolerated in relapsed multiple myeloma.

BACKGROUND: The standard schedule of bortezomib requires frequent infusions and is often associated with dose-dependent, adverse effects such as sensory neuropathy and thrombocytopenia. Because of the known additive effect between bortezomib and glucocorticoid, we explored weekly bortezomib/methylprednisolone in patients with relapsed multiple myeloma. PATIENTS AND METHODS: Twenty-nine patients were treated at Indiana University with bortezomib (1.3 mg/m2) and methylprednisolone (500-2000 mg) intravenously on days 1, 8, and 15 of 28-day cycles. Response was evaluated using the Blade criteria. Twenty-one patients (70%) had previous stem cell transplantation, and 13 were in third relapse or higher. RESULTS: A response was observed in 18 patients (62%): 1 (3%) complete response, 1 (3%) near complete response, and 16 (55%) partial responses. Six (21%) had stable disease, and 5 (17%) had disease progression. The median time to progression, which was defined from the beginning of therapy until progression, was 6.6 months (95% confidence interval, 6.4-9.2 months). The median number of treatment cycles was 6 (range, 2-12 cycles). The median overall survival was 20.2 months (lower 95% confidence interval, 13.1 months). The most common toxicities were fatigue and gastrointestinal disturbances. Grade >or= 3 adverse effects included neuropathy (2 grade 3), gastrointestinal side effects (1 grade 3), and congestive heart failure (1 grade 3). CONCLUSION: The weekly bortezomib/methylprednisolone regimen was well tolerated and yielded a response rate comparable with the standard schedule of bortezomib alone. Our data support further investigation of this regimen in larger patient cohorts.

Proteasome inhibition in cancer therapy.

Multiple myeloma is an incurable malignancy diagnosed for approximately 15,000 individuals in the United States each year. The advances in high-dose chemotherapy and transplantation have improved the overall survival rates and allowed individuals to remain off therapy for longer periods, but relapses are inevitable. The novel proteasome inhibitor, bortezomib, is the first in its class to be approved for patients with relapsed multiple myeloma. This article discusses the proteasome pathway and its role in the regulation of cell growth and survival. During clinical trials, most side effects were manageable with appropriate interventions. The common toxicities are outlined in this article, along with symptom management guidelines for the infusion nurse. The role of the infusion-oncology nurse is vital to ensuring the safe and appropriate administration of bortezomib, and the nurse plays a key role in the ongoing care of these patients.