Biomib

As monotherapy or in combination w/ pegylated liposomal doxorubicin or dexamethasone for the treatment of adults w/ progressive multiple myeloma who have received at least 1 prior therapy & who have already undergone or are unsuitable for hematopoietic stem cell transplantation. In combination w/ melphalan & prednisone for the treatment of adults w/ previously untreated multiple myeloma who are not eligible for high-dose chemotherapy w/ hematopoietic stem cell transplantation. In combination w/ dexamethasone, or w/ dexamethasone & thalidomide for the induction treatment of adults w/ previously untreated multiple myeloma who are eligible for high-dose chemotherapy w/ hematopoietic stem cell transplantation. In combination w/ rituximab, cyclophosphamide, doxorubicin & prednisone for the treatment of adults w/ previously untreated mantle cell lymphoma who are unsuitable for hematopoietic stem cell transplantation.

IV/SC Adult Progressive multiple myeloma who have received at least 1 prior therapy General dosing: 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 followed by 10-day rest period (days 12-21) in 21-day treatment cycle. At least 72 hr should elapse between consecutive doses. Monotherapy: Patient should receive 2 cycles of bortezomib after complete response is confirmed. Neuropathy (grade 1 w/ pain or grade 2 (moderate symptoms) Reduce to 1 mg/m² or change bortezomib treatment schedule to 1.3 mg/m² once/wk. Combination therapy w/ pegylated liposomal doxorubicin: 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in 21-day treatment cycle. At least 72 hr should elapse between consecutive doses. Administer pegylated liposomal doxorubicin 30 mg/m² on day 4 of the treatment cycle as 1 hr IV infusion. Combination therapy w/ dexamethasone: 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle. At least 72 hr should elapse between consecutive doses. Administer oral dexamethasone 20 mg on days 1, 2, 4, 5, 8, 9, 11 & 12 of the treatment cycle. Progressive multiple myeloma who are unsuitable for hematopoietic stem cell transplantation Combination therapy w/ melphalan & prednisone: Administer 1.3 mg/m² twice wkly on days 1, 4, 8, 11, 22, 25, 29 & 32 for cycles 1-4, then 1.3 mg/m² once wkly on days 1, 8, 22 & 29 for cycles 5-9. At least 72 hr should elapse between consecutive doses. Administer oral melphalan & prednisone on days 1-4 of the 1st wk of each treatment cycle. Previously untreated multiple myeloma eligible for hematopoietic stem cell transplantation (induction therapy) Combination therapy w/ dexamethasone: 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8, & 11 followed by 10-day rest period (days 12-21) in 21-day treatment cycle. At least 72 hr should elapse between consecutive doses of bortezomib. Administered oral dexamethasone 40 mg on days 1, 2, 3, 4, 8, 9, 10 & 11 of the treatment cycle. Combination therapy w/ dexamethasone & thalidomide: 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 followed by 17-day rest period (days 12-28) in a 28-day treatment cycle. At least 72 hr should elapse between consecutive doses. Administer oral dexamethasone 40 mg on days 1-4 & 8-11 of the treatment cycle; oral thalidomide 50 mg on days 1-14 & if tolerated, may increase to 100 mg on days 15-18, thereafter may be further increased to 200 mg daily from cycle 2. 2 additional cycles are recommended in patient w/ at least partial response. Previously untreated mantle cell lymphoma Combination therapy w/ rituximab, cyclophosphamide, doxorubicin & prednisone: 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8, & 11 followed by 10-day rest period (days 12-21) in a 21-day treatment cycle. At least 72 hr should elapse between consecutive doses. Patients w/ a response first documented at cycle 6, 2 additional treatment cycles may be given. Administer oral prednisone at 100 mg/m² on days 1, 2, 3, 4 & 5 of each treatment cycle. Administer on day 1 of each 3-wk treatment cycle as IV infusions: rituximab 375 mg/m², cyclophosphamide 750 mg/m², & doxorubicin 50 mg/m². Dose adjustments during treatment & re-initiation of treatment for bortezomib monotherapy & combination therapy: Re-initiate at 25% reduced dose (1.3 mg/m² reduced to 1 mg/m²; 1 mg/m² reduced to 0.7 mg/m²). Moderate to severe hepatic impairment Reduce dose to 0.7 mg/m² during the 1st treatment cycle, & a subsequent dose escalation to 1 mg/m² or further dose reduction to 0.5 mg/m² may be considered based on patient tolerability.

Hypersensitivity to bortezomib, boron & mannitol. Acute diffuse infiltrative pulmonary & pericardial disease. Intrathecal administration.

Patients w/ moderate to severe thrombocytopenia & risk factors for bleeding. Discontinue if posterior reversible encephalopathy syndrome & progressive multifocal leukoencephalopathy (PML) develops. Progressive multifocal leukoencephalopathy. Peripheral & autonomic neuropathy; seizures. Heart failure, QT prolongation, hypotension. Pulmonary disorders. GI toxicity. Tumor lysis syndrome. Herpes zoster reactivation. HBV reactivation & infection. Amyloidosis. Potentially immune complex-mediated reactions. Hepatic & renal effects. May affect ability to drive & use machines. Not to be used during pregnancy & advised not to breastfeed 2 mth after treatment. Women of childbearing potential should avoid becoming pregnant during & 3 mth after treatment. Childn <18 yr.

Nausea, diarrhea, constipation, vomiting, fatigue, asthenia, pyrexia, transient thrombocytopenia, anemia, neutropenia, peripheral neuropathy (including motor & sensory), headache, paresthesia, decreased appetite, dyspnea, rash, herpes zoster, & myalgia.

May increase exposure w/ ketoconazole; melphalan-prednisone. May decrease exposure & efficacy w/ rifampicin, St. John's wort (Hypericum perforatum), carbamazepine, phenytoin, phenobarb. May increase risk of hypoglycemia &/or hyperglycemia w/ oral antidiabetics. Amiodarone, anti-virals, INH, nitrofurantoin, statins.

Targeted Cancer Therapy

L01XG01 - bortezomib ; Belongs to the class of proteasome inhibitors. Used in the treatment of cancer.

Rx