IMpower133 is a Phase III, multicentre, double-blinded, randomised placebo-controlled study evaluating the efficacy and safety of Tecentriq in combination with chemotherapy (carboplatin and
etoposide) vs.
(carboplatin and
etoposide) alone in chemotherapy-naive adults with ES-SCLC.
The drug candidate
etoposide has variable oral bioavailability ranging from 24% to 74% and has a terminal half-life of 1.5 h by intravenous route and 0.44 h by oral route.
The standard of care for Stage IIA - Good risk MGCTis either four cycles of EP regimen (
Etoposide 100mg/m2, Cisplatin 20 mg/m2) or three cycles of BEP regimen (Bleomycin 30 units every week,
Etoposide 100mg/m2, Cisplatin 20 mg/m2), every three weeks.10 We usually use EP regimen to avoid Bleomycin pulmonary toxicity as an institutional practice, moreover in our patient there was baseline dyspnea secondary to his recent TCM which precluded Bleomycin use.Though Cisplatin remains the cornerstone of GCT chemotherapy and a standard of care, however it is also related to some other rare side effects like vasculitis, cardiomyopathy and vascular thrombosis.
(1,4) Other adverse prognostic factors include age >30, thrombocytopenia, male sex, low albumin, and lack of
etoposide therapy.
In our centre, adolescent and adult ES patients (age > 16 years) with localized and metastatic disease have been treated between 1990 and 2014 with two alternating chemotherapy regimens: VIA (vincristine, ifosfamide, and doxorubicin) and VIP (
etoposide, ifosfamide, and cisplatin).
The effect of siRNA,
Etoposide, and RES on growth inhibition was assessed as percentage of cell viability; control cells (only ethanol or scrambled siRNA) were considered 100% viable.
CS has two settings, either hours after the start of combined CT based on bleomycin,
etoposide, and cisplatin (BEP) or much less frequently as an initial presentation of advanced disease with no relation to treatment, as in our patient [4].
Cisplatin (Accord Healthcare Limited),
etoposide (Teva Italia), irinotecan (Campo, Pfizer), and topotecan (GlaxoSmithKline) were kindly provided by the pharmacy of our institution.
In the 1980s when the combination of cisplatin, vinblastine, and bleomycin (PVB) was the standard first-line regimen, the combination of
etoposide, ifosfamide, and cisplatin (VIP) was the most common salvage regimen since it included two drugs not administered in the first-line setting.
Before the introduction of these newer options, as well as several targeted treatments such as Cyclin-Dependent Kinase 4/6 inhibitors and mechanistic Target of Rapamycin (mTOR) inhibitors, oral
etoposide had been one of the few available systemic treatments in the oncology armamentarium for advanced breast cancer.
The patient recovered well after surgery and was started on a regimen of bleomycin,
etoposide, and cisplatin expected to last at least six cycles.