Lurbin

Lurbin is indicated for the treatment of adult patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy. This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Dosage & Administration

The recommended dosage of Lurbinectedin is 3.2 mg/m
2
by intravenous infusion over 60 minutes every 21 days until disease progression or unacceptable toxicity.
Initiate treatment with Lurbinectedin only if absolute neutrophil count (ANC) is at least 1,500 cells/mm
3
and platelet count is at least 100,000/mm
3
.

The most common adverse reactions, including laboratory abnormalities, (≥20%) are leukopenia, lymphopenia, fatigue, anemia, neutropenia, increased creatinine, increased alanine aminotransferase, increased glucose,
thrombocytopenia, nausea, decreased appetite, musculoskeletal pain, decreased albumin, constipation, dyspnea, decreased sodium, increased aspartate aminotransferase, vomiting, cough, decreased magnesium and diarrhea.

Myelosuppression
: Monitor blood counts prior to each administration. Initiate treatment with Lurbin only if baseline neutrophil count is ≥1,500 cells/mm3 and platelet count is ≥100,000/mm3. Withhold, reduce the dose, or permanently discontinue Lurbin based on severity.
Hepatotoxicity
: Monitor liver function tests prior to initiating Lurbin, periodically during treatment and as clinically indicated. Withhold, reduce the dose, or permanently discontinue Lurbin based on severity.
Extravasation Resulting in Tissue Necrosis
: Consider use of a central venous catheter to reduce the risk of extravasation. Monitor patients for signs and symptoms of extravasation during the Lurbin infusion. If extravasation occurs, immediately discontinue the infusion, remove the infusion catheter, and monitor for signs and symptoms of tissue necrosis.
Rhabdomyolysis
: Monitor creatine phosphokinase (CPK) prior to initiating Lurbin and periodically during treatment as clinically indicated. Withhold, reduce the dose, or permanently discontinue Lurbin based on severity.
Embryo-Fetal Toxicity
: Can cause fetal harm. Advise females and males of reproductive potential of the potential risk to a fetus and to use an effective method of contraception.

Lurbinectedin is an alkylating drug that binds guanine residues in the minor groove of DNA, forming adducts and resulting in a bending of the DNA helix towards the major groove. Adduct formation triggers a cascade of events that can affect the subsequent activity of DNA binding proteins, including some transcription factors, and DNA repair pathways, resulting in perturbation of the cell cycle and eventual cell death. Lurbinectedin inhibited human monocyte activity in vitro and reduced macrophage infiltration in implanted tumors in mice.