Epirubicin/paclitaxel/etoposide in extensive-stage small-cell lung cancer: a phase I–II study

Abstract

The aim of this study was to evaluate feasibility and toxicity of escalating doses of epirubicin and paclitaxel plus fixed dose of etoposide and to define the activity of the triplet in extensive disease small-cell lung cancer. Thirteen patients entered the phase I study: the maximum tolerated doses were epirubicin (EpiDX) 90 mg m À2 and paclitaxel (P) 175 mg m À2 with febrile neutropenia as dose-limiting toxicity. The recommended schedule for this regimen for the phase II study was EpiDX 75 mg m À2 , P 175 mg m À2 , etoposide (E) 100 mg m À2 intravenous (fixed dose) days 1 -3 with courses repeated every 21 days. The prophylactic use of colonystimulating factors (CSFs) was not allowed. Twenty patients entered the phase II trial: median age was 61 years (range 50 -70), median Eastern Cooperative Oncology Group performance status 0 (0 -2); nine patients had visceral disease and 17 had more than two metastatic sites. A total of 100 courses were administered with a median of 5 (range 1 -6) per patients. Main toxicity (NCI-CTC) was myelosuppression: neutropenia grades 3 and 4 in 16 and 35% of the courses, respectively. Seven episodes of febrile neutropenia were documented and one patient required hospital admission. Nonhaematological toxicity was moderate. Seven out of 19 evaluable patients achieved a complete response (37%), nine patients (47.3%) a partial response with an overall response rate of 84.2% ((95% confidence interval ¼ 60.4 -96.6)). In this poor prognostic population of patients the triplet epirubicin/paclitaxel/ etoposide showed high antitumour activity with mild nonhaematological side effects. The use of CSFs should be able to improve the haematological profile.

Solamargine Enhances HER2 Expression and Increases the Susceptibility of Human Lung Cancer H661 and H69 Cells to Trastuzumab and Epirubicin

“…The chromosomal location of both HER2 and TOP2A is 17q21-22 , . Epirubicin is a TOP2 inhibitor and is employed as a base in single or combination chemotherapy for solid tumors, including lung cancer cells . Several studies have indicated that HER2 and TOP2A overexpression is not significantly correlated with failure chemotherapy, patient survival, recurrence, or overall histologic grade , .…”

Real‐life second‐line epirubicin–paclitaxel regimen as treatment of relapsed small‐cell lung cancer: EpiTax study

“…20 The dosage was determined according to previous phase II studies in SCLC. 14 , 17 Patients with a history of BMs were included. Exclusion criteria were written or oral refusal to participate expressed during the lifetime, composite tumor or another subtype of lung carcinoma, and SCLC patients not treated with the study regimen.…”

“…15 Two phase II studies highlighted the activity of epirubicin in SCLC both as monotherapy or when combined with other drugs. 16 , 17 Recently, Pasello et al reported retrospective data of 68 patients treated with epirubicin at 70 mg/m 2 combined with paclitaxel at 135 mg/m 2 in the second line 18 and highlighted the efficacy of this association. Partial response (PR) and stable disease (SD) were obtained in 30% and 34% of cases, respectively, with a median PFS and OS reaching 21.8 and 26.5 weeks, respectively.…”

“…Nevertheless, Torti et al suggested a greater cardiac tolerance with epirubicin compared with doxorubicin 15 . Two phase II studies highlighted the activity of epirubicin in SCLC both as monotherapy or when combined with other drugs 16,17 . Recently, Pasello et al reported retrospective data of 68 patients treated with epirubicin at 70 mg/m 2 combined with paclitaxel at 135 mg/m 2 in the second line 18 and highlighted the efficacy of this association.…”

Simultaneous LC‐MS/MS bioanalysis of etoposide and paclitaxel in mouse tissues and plasma after oral administration of self‐microemulsifying drug‐delivery systems

“…Therefore, combination chemotherapy is required and many medical oncologists are exploring new drug combinations for improved chemotherapy. A number of clinical trials have been carried out to verify the chemotherapy effect of combination use of ETP and paclitaxel (Dongiovanni, Buffoni, et al, ; Reck, von Pawel, et al, , ; Tibaldi, Prochilo, et al, ). A recent study indicated that the combination of PTX and ETP in a polymer–lipid hybrid nanoparticle system improved the efficacy for osteosarcoma in vitro (Duan, Li, et al, ).…”