多发性骨髓瘤（MM）是发生在B淋巴细胞的恶性浆细胞病。近日，美国食品与药物管理局（FDA）批准了卡非佐米(carfilzomib)用于治疗之前接受至少2种药物（包括硼替佐米和免疫调节剂治疗）的MM患者。
卡非佐米(carfilzomib)是经静脉给药的新一代蛋白酶抑制剂。为了评估该药的安全性和有效性，一项研究纳入266例之前至少接受过2种治疗方法（包括硼替佐米和沙利度胺）的患者。评估治疗后患者的肿瘤完全或部分消失情况（整体有效率）。结果显示，患者的整体有效率为23%，中位缓解时间为7.8个月。
在超过30%的受试者中观察到卡非佐米(carfilzomib)的最常见不良反应包括疲劳，血细胞计数和血小板计数偏低，呼吸困难，腹泻和发热。严重的不良反应包括心衰和呼吸困难，患者一旦出现严重不良反应，应密切监测和停止该药的治疗。
Manufacturer:
Onyx Pharmaceuticals
Pharmacological Class:
Proteasome inhibitor.
Active Ingredient(s):
Carfilzomib 60mg/vial; lyophilized pwd for IV inj after reconstitution; preservative-free.
Indication(s):
Treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy.
Pharmacology:
Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. Carfilzomib had antiproliferative and proapoptotic activities in vitro in solid and hematologic tumor cells.
Clinical Trials:
The safety and efficacy of Kyprolis were evaluated in a single-arm, multicenter clinical trial. Two hundred and sixty-six patients with relapsed multiple myeloma who had received at least two prior therapies (including bortezomib and thalidomide and/or lenalidomide) were enrolled. Patients were enrolled in the trial whose disease had a ≤25% response to the most recent therapy or had disease progression during or within 60 days of the most recent therapy. Patients were excluded from the trial with total bilirubin levels ≥2 × upper limit of normal; CrCl <30mL/min; NYHA Class III to IV CHF; symptomatic cardiac ischemia; myocardial infarction (MI) within the last 6 months; peripheral neuropathy Grade 3 or 4, or peripheral neuropathy Grade 2 with pain; active infections requiring treatment; and pleural effusion.
Kyprolis was administered intravenously over 2–10 minutes on two consecutive days each week for three weeks, followed by a 12-day rest period (28-day treatment cycle), until disease progression, unacceptable toxicity, or for a maximum of 12 cycles. Patients received 20mg/m2 at each dose in Cycle 1, and 27mg/m2 in subsequent cycles. To reduce the incidence and severity of fever, rigors, chills, dyspnea, myalgia, and arthralgia, dexamethasone 4mg by mouth or by IV infusion was administered prior to all Kyprolis doses during the first cycle and prior to all Kyprolis doses during the first dose-escalation (27mg/m2) cycle. Dexamethasone premedication (4mg orally or intravenously) was reinstated if these symptoms reappeared during subsequent cycles.
The median number of cycles started was four.
The primary endpoint was the overall response rate (ORR) as determined by Independent Review Committee using International Myeloma Working Group criteria. The ORR (stringent complete response [sCR] + complete response [CR] + very good partial response [VGPR] + partial response [PR]) was 22.9% (95% CI: 18.0, 28.5) (N=266). The median duration of response was 7.8 months (95% CI: 5.6, 9.2).
Legal Classification:
Rx
Adults:
See literature. Premedicate with dexamethasone prior to all Cycle 1 doses, during 1st dose escalation and if infusion reactions occur. Give by IV over 2–10 minutes, on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17–28). In Cycle 1: 20mg/m2 per each dose, if tolerated increase to 27mg/m2 starting in Cycle 2 and subsequent cycles; continue until disease progression or unacceptable toxicity occurs. On dialysis: give dose after session. Toxicity dose modification: see literature.
Children:
Not established.
Warnings/Precautions:
Risk of cardiac complications (eg, CHF, MI, pulmonary edema); monitor and manage promptly if occurs. Pulmonary hypertension; if suspected, withold therapy until resolved; may consider restarting after reevaluate. Monitor for dyspnea or tumor lysis syndrome, and manage promptly if occurs; interrupt therapy until resolved. Maintain adequate hydration. Monitor platelets frequently during therapy. Hepatic impairment (monitor enzymes). Pregnancy (Cat. D); avoid. Nursing mothers: not recommended.
Adverse Reaction(s):
Fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, pyrexia; cardiac events, pulmonary HTN, infusion reactions, tumor lysis syndrome, hepatic toxicity/failure.
How Supplied:
Single use vial—1
Last Updated:
7/30/2012