Expanding Role of Bortezomib in Multiple Myeloma: Nursing Implications

Kathleen Colson, RN, BSN, BS; Deborah S. Doss, RN, OCN; Regina Swift, RN, BSN; Joseph Tariman, RN, APN, MN, BC, OCN

Disclosures

Cancer Nurs. 2008;31(3):239-249. 

In This Article

Practical Considerations With Bortezomib

Oncology nurses are on the front line of patient care, playing a key role in administering treatment, managing side effects, and helping patients (and their families) to understand their treatment. Nurses are often the first to identify patients' side effects and can discuss their concerns and provide information and reassurance.

Bortezomib is injected by intravenous push directly into a peripheral vein or through an infusion port for 3 to 5 seconds. The line should be flushed with normal saline. A local skin reaction may occur after administration and was reported in 5% of patients in clinical trials.[20] Vital signs, blood counts, chemistries, and neurological status should be assessed before bortezomib is administered and monitored throughout therapy ( Table 2 ).

The recommended dose of bortezomib is 1.3 mg/m2 twice weekly for 2 weeks (days 1, 4, 8, and 11) followed by a 10-day rest period (days 12-21). For extended therapy of more than 8 cycles, bortezomib may be administered at the standard dose and schedule as above, or on a maintenance schedule of once weekly for 4 weeks (days 1, 8, 15, and 22) followed by a 13-day rest period (days 23-35).[20] There must be at least 72 hours between doses; more frequent dosing may lead to more frequent or more severe side effects.

Duration of therapy depends on the risks and benefits of continuing, based on each's medical history and current condition. In the APEX, SUMMIT, and CREST trials, 39%,39%, and 27% of patients, respectively, completed 8 cycles of bortezomib 1.3 mg/m2.[9,10,12] In the APEX trial, the overall median number of cycles received was 6, and responders (CR + PR) received a median of 10 cycles. The best response in terms of M-protein reduction was seen in cycle 4 or later in 66% of patients, with approximately 20% achieving their best response in cycle 8 or later; patients with 100% M-protein reduction tended to have a longer duration of response than those with ≥50% but <100% M-protein reduction, indicating the potential benefit of a longer duration of therapy.[9] In an extension study of SUMMIT and CREST, patients received a median of 14 cycles of bortezomib (range, 7-32)[21] without new cumulative toxicities.

Nurses must be familiar with the bortezomib dose-modification guidelines. Bortezomib should be withheld if patients experience grade 3 nonhematologic or grade 4 hematologic toxicities (National Cancer Institute Common Terminology Criteria for Adverse Events Version 3.0), excluding neuropathy. When symptoms have resolved, treatment can be reinitiated at approximately 75% of the original dose.[20] For neuropathic pain or peripheral neuropathy, the scheme shown in Table 3 is implemented.

Dose modification should only be used because of toxicity; when modified appropriately, bortezomib remains active and the intensity of adverse effects can be reduced.

The benefits of bortezomib are not restricted to improvements in MM-related end points. It is important that nurses are aware of these added benefits so that they can discuss treatment expectations with patients. One of the greatest concerns for cancer patients is the impact of their treatment on psychosocial quality of life (QOL). Notably, QOL may be predictive of survival in MM.[23] Nurses administering bortezomib therapy can reassure patients that QOL is likely to improve during therapy rather than deteriorate. In the APEX trial, bortezomib treatment was associated with better health-related QOL than high-dose dexamethasone.[24] In the SUMMIT study, bortezomib led to QOL improvements from baseline in responding patients.[25]

Bortezomib also has a positive effect on bone metabolism,[26,27,28,29] and may therefore help control or improve MM-related bone disease, as well as the MM itself,[28] potentially resulting in fewer bone fractures. In patients with MM-related bone disease, the activity of osteoblasts, which make bone, is impaired, whereas osteoclast activity is increased, leading to osteoporosis, osteolytic lesions, and, ultimately, bone resorption. In a retrospective analysis of relapsed and/or refractory MM patients from 3 studies of bortezomib therapy, Zangari et al[26] showed that response to bortezomib was associated with osteoblastic activation, as evidenced by significant increases in alkaline phosphatase from baseline. The difference in alkaline phosphatase increase between patients responding to bortezomib, and nonresponders was shown to be significant; a similar difference was not seen in patients randomized to dexamethasone on the APEX study.[26] In another study involving 25 patients receiving bortezomib alone or in combination with dexamethasone, levels of specific markers of osteoblast activity were shown to increase after bortezomib therapy, regardless of response to treatment.[27] Bortezomib also inhibits osteoclast activity and reduces osteoclastic bone resorption, as shown by reductions in specific markers of osteoclast activity and osteoclast regulators.[28,29] In one study on the effect of bortezomib on bone remodeling in 34 relapsed MM patients, bortezomib treatment significantly reduced serum levels of osteoblast inhibitors, osteoclast regulators, and bone resorption markers, regardless of response to treatment, thereby leading to the normalization of the bone remodeling process through the increase of bone formation and the reduction of bone resorption.[29]

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