The results demonstrate that BDR produces rapid and durable responses, along with high rates of response and complete remissions in WM. Herpes zoster prophylaxis is necessary with BDR, and reversible peripheral neuropathy was the most common toxicity leading to premature discontinuation of bortezomib in 61% of patients. Exploration of alternative schedules for bortezomib administration that includes weekly dosing should be pursued.
High standards of care are desirable for patients in any setting who receive chemotherapy by any route. Patients who self-administer oral chemotherapy are subject to risks of adverse effects similar to those who receive i.v. chemotherapy. Safeguards to prevent medication error in these patients may not be achieved to the same degree as for patients receiving i.v. drugs in an institutional setting. This article describes the differences between typical administration standards for i.v. chemotherapy versus oral chemotherapy. The process of oral chemotherapy provision is examined, with examples of drug characteristics and patient features important in each step. Recommendations are made for improving the care of patients receiving oral chemotherapy medications, particularly in the home setting.
Background: Bortezomib (VELCADE®, Vel) and lenalidomide (Revlimid®, Rev) are both highly effective agents in multiple myeloma (MM). Preclinical studies show Rev sensitizes MM cells to Vel and dexamethasone (Dex), suggesting combination therapy may enhance clinical activity. This phase 1 dose-escalation study aimed to determine MTD and activity of Rev-Vel +/− Dex combination therapy in patients (pts) with relapsed and/or refractory MM. Methods: Eight cohorts (≥3 pts each) were planned, with dosing of Vel 1.0 or 1.3mg/m2 (d 1, 4, 8, 11) and Rev 5, 10, 15, or 20mg (d 1–14), in 21-d cycles. Dex 40mg (on day of and day after each Vel dose) could be added in pts with PD. NCI CTCAE v3.0 was used for toxicity assessment; DLT was defined as any grade (G) ≥3 non-hematologic toxicity, G4 neutropenia for ≥5 d and/or neutropenic fever, or platelets <10,000/mm3 on >1 occasion despite transfusion. Response was assessed by modified EBMT criteria. Results: 28 pts were enrolled in cohorts 1–6 (Rev 5–15mg, Vel 1.0–1.3mg/m2) plus 10 additional pts at the MTD (Dose Level 5), including 12 with relapsed and 26 with relapsed and refractory MM (n=38). Among 25 men and 13 women, median age was 60yrs (range: 37–79), and median no. of prior therapies was 5 (range: 1–13), including 23 pts with prior SCT, 23 with prior Vel, 6 with prior Rev, and 36 with prior thalidomide (Thal). One DLT was observed in cohort 4 (Rev 10mg–Vel 1.3mg/m2; transient G3 hyponatremia). DLT was reached in cohort 6 (Rev 15mg–Vel 1.3mg/m2) with 1 episode of G3 HZV reactivation (successfully treated with acyclovir) and 1 G4 neutropenia (reversed with GCSF support and dose reduction). MTD was therefore declared at Rev 15mg–Vel 1.0mg/m2. In total, 5 pts had dose reductions for Vel, 6 pts for Rev, and 5 pts for both Rev and Vel. No significant (G≥3) fatigue or peripheral neuropathy has been seen. No anticoagulant prophylaxis was required and only 1 pt had DVT while on Rev alone. In 36 evaluable pts, the overall response rate (CR+PR+MR) is 58% (90% CI: 46%, 75%), including 6% CR/nCR (Table) after a median of 6 cycles (range: 4–17). Responses were durable (median 6 months, range: 1–26), and 11 pts remain on therapy beyond 1 year. Dex has been added in 14 pts with PD, resulting in PR/MR/SD in 10 (71%), with just 1 pt experiencing Dex-related G2 diarrhea and fatigue, which prompted discontinuation of therapy. Conclusions: Rev-Vel +/− Dex is well tolerated and very active with durable responses seen in pts with heavily pretreated relapsed and/or refractory MM, including pts who have had prior Rev, Vel, Thal and SCT. An MTD of Rev 15mg–Vel 1.0mg/m2 has been defined, with Phase 2 studies now ongoing in both newly diagnosed and relapsed/refractory MM. Best responses by Rev-Vel cohort (EBMT criteria) Cohort Rev-Vel dose Vel 1.0mg/m2 Vel 1.3mg/m2 1–2 Rev 5mg 2PR, 1MR 1CR, 2PR 3–4 Rev 10mg 1nCR, 2PR 2PR, 2MR, 1SD, 1PD 5–6 Rev 15mg 2PR, 4MR, 7SD, 1PD 2 PR, 5SD
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