lurbinectedin

Lurbinectedin instructions
Common name: lurbinectedin
Trade name: Zepzelca
Full names: lurbinectedin, lurbinectedin, lurbinectedin, Z epzelca, lurbinectedin

Indications:
Lurbinectedin is indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC) who have disease progression during/after platinum-based chemotherapy.

Usage and Dosage:
Recommended dose:
The recommended dose of rubitidine is 3.2mg/m2, intravenously infused for 60 minutes every 21 days until disease progression or unacceptable toxicity occurs.
Only when the absolute neutrophil count (ANC) is ≥1,500 cells/mm3 and the platelet count is ≥100,000 cells/mm3, treatment with rupitidine should be started.

Adverse Reactions:
If you have signs of an allergic reaction: hives; difficulty breathing; swelling of the face, lips, tongue, or throat, seek immediate medical attention.

Contact your doctor immediately if:
Easily bruised, unusual bleeding, purple or red spots under the skin;
Low red blood cells (anemia) - pale skin, unusual fatigue, dizziness or shortness of breath, cold hands and feet;
Low white blood cell count - fever, mouth ulcers, skin ulcers , sore throat, cough, trouble breathing;
Sepsis symptoms - confusion, fever or chills, severe drowsiness, fast heartbeat, shortness of breath, feeling very sick; or
Liver problems - loss of appetite, stomach pain (upper right side), fatigue, itching, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).

Common side effects may include:
low blood count; cough, trouble breathing; nausea, vomiting, loss of appetite; increased thirst or urination; diarrhea, constipation; muscle or joint pain; feeling tired; or abnormal blood tests.

This is not a complete list of adverse reactions. Other adverse reactions may occur. Please consult your doctor for details.

Taboos:
None.

Notes:
Myelosuppression: In clinical trials, 554 patients with advanced solid tumors were treated with rupitidine. 41% of patients developed grade 3 or 4 neutropenia. The median time to onset was 15 days and the median duration was 7 days. The incidence of febrile neutropenia was 7%. The incidence of sepsis was 2% and the fatality rate was 1% (all cases occurred in patients with solid tumors other than SCLC). Grade 3 or 4 thrombocytopenia occurred in 10% of patients, with a median onset of 10 days and a median duration of 7 days. Grade 3 or 4 anemia occurred in 17% of patients.
Hepatotoxicity: In clinical trials, 554 patients with advanced solid tumors were treated with rupitidine. The incidences of grade 3 ALT and AST elevations were 6% and 3%, respectively, and the incidences of grade 4 ALT and AST elevations were 0.4% and 0.5%, respectively. The median onset of grade 3 or higher transaminase elevations was 8 days (range: 3-49), and the median duration was 7 days.
Embryotoxicity: Based on animal test data and its mechanism of action, rupitidine taken by pregnant women can cause harm to the fetus. During the organogenesis period, a single intravenous dose of lubitidine (approximately 0.2 times the clinical dose of 3.2 mg/m2) was administered to pregnant rats, resulting in 100% embryonic lethality. Inform pregnant women of the potential risk to the fetus. Advise female patients to use effective contraception during treatment with rupitidine and for 6 months after the last dose. Advise male patients to use effective contraception with their female partners (of reproductive potential) during treatment with rupitidine and for 4 months after the last dose.

Storage:
Store refrigerated at 2° to 8°C (36° to 46°F).
Rupitidine is a dangerous drug. Follow applicable special handling and disposal procedures.

Mechanism of action:
Rupitidine is an alkylating drug that binds to guanine residues in the minor groove of DNA to form an adduct, causing the DNA helix to bend toward the major groove. The formation of adducts triggers a series of events that affect the subsequent activity of DNA-binding proteins, including some transcription factors and DNA repair pathways, leading to cell cycle disorders and ultimately cell death.
In vitro, rupitidine inhibits human monocyte activity and reduces macrophage infiltration in mouse xenograft tumors.

Safety and Efficacy:
PM1183-B-005-14 (Trial B-005; NCT02454972) is a multicenter, open-label, multi-arm trial evaluating the efficacy of rupitidine monotherapy in the treatment of advanced or metastatic solid tumors. A group of small cell lung cancer (SCLC) patients whose disease progressed during/after platinum-based chemotherapy were given intravenous infusion of rupitidine 3.2 mg/m2 every 21 days (one cycle), and the median number of medication cycles received was 4 (range 1-24).
The primary efficacy outcome measure is investigator-assessed overall response rate (ORR). Other efficacy outcome measures include duration of response (DoR) and ORR as assessed by the Independent Review Committee (IRC) according to RECIST v1.1 criteria.
A total of 105 patients with small cell lung cancer (SCLC) whose disease progressed during/after platinum-based chemotherapy were recruited. The final results assessed by researchers were: ORR was 35%, and the median DoR was 5.3 months; the results assessed by IRC were: ORR was 30%, and the median DoR was 5.1 months.