Efficacy and safety of lurbinectedin and doxorubicin in relapsed small cell lung cancer. Results from an expansion cohort of a phase I study

• DOI: 10.1007/s10637-020-01025-x
• Publication Date: 2021-03-11T09:12:30Z
• Authors: María Eugenia Olmedo; Martin Forster; Victor Moreno; María Pilar López...; Irene Braña; Michael Flynn; Bernard Doger; María de Miguel; José Antonio Lópe...; Rafael Núñez; Carmen Kahatt; Martin Cullell-Young; Ali Zeaiter; Emiliano Calvo
• Keywords: Lurbinectedin; Male; Lung Neoplasms; Maximum Tolerated Dose; :neoplasias::neoplasias por localización::neoplasias torácicas::neoplasias del tracto respiratorio::neoplasias pulmonares::neoplasias de los bronquios::carcinoma broncogénico::carcinoma pulmonar de células pequeñas [ENFERMEDADES]; :Otros calificadores::Otros calificadores::/farmacoterapia [Otros calificadores]; Antineoplastic Agents; Kaplan-Meier Estimate; :Other subheadings::Other subheadings::/drug therapy [Other subheadings]; Heterocyclic Compounds, 4 or More Rings; Quimioteràpia combinada; 03 medical and health sciences; 0302 clinical medicine; :Therapeutics::Therapeutics::Drug Therapy::Antineoplastic Protocols::Therapeutics::Drug Therapy::Antineoplastic Combined Chemotherapy Protocols [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]; Phase I Studies; Antineoplastic Combined Chemotherapy Protocols; Humans; Aged; PM01183; Small cell lung cancer; Dose-Response Relationship, Drug; :terapéutica::terapéutica::farmacoterapia::protocolos antineoplásicos::terapéutica::farmacoterapia::protocolos de quimioterapia antineoplásica combinada [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]; :diagnóstico::pronóstico::resultado del tratamiento [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS]; Middle Aged; :Diagnosis::Prognosis::Treatment Outcome [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT]; Small Cell Lung Carcinoma; Progression-Free Survival; 3. Good health; Doxorubicin; Drug Resistance, Neoplasm; Avaluació de resultats (Assistència sanitària); Phase I study; :Neoplasms::Neoplasms by Site::Thoracic Neoplasms::Respiratory Tract Neoplasms::Lung Neoplasms::Bronchial Neoplasms::Carcinoma, Bronchogenic::Small Cell Lung Carcinoma [DISEASES]; Female; Neoplasm Recurrence, Local; Pulmons - Càncer - Tractament; Carbolines

Summary Background A phase I study found remarkable activity and manageable toxicity for doxorubicin (bolus) plus lurbinectedin (1-h intravenous [i.v.] infusion) on Day 1 every three weeks (q3wk) as second-line therapy in relapsed small cell lung cancer (SCLC). An expansion cohort further evaluated this combination. Patients methods Twenty-eight patients with SCLC after no more than one line of cytotoxic-containing chemotherapy were treated: 18 (64%) sensitive disease (chemotherapy-free interval [CTFI] ≥90 days) ten (36%) resistant (CTFI <90 days; including six refractory [CTFI ≤30 days]). Results Ten showed confirmed response (overall rate [ORR] = 36%); median progression-free survival (PFS) 3.3 months; overall (OS) 7.9 months. ORR was 50% (median PFS 5.7 OS 11.5 months) 10% 1.3 4.6 months). The main transient reversible myelosuppression. Treatment-related non-hematological events (fatigue, nausea, decreased appetite, vomiting, alopecia) mostly mild or moderate. Conclusion Doxorubicin 40 mg/m 2 2.0 q3wk has shown noteworthy a safety profile. combination is being an ongoing, randomized III trial. Clinical trial registration www.ClinicalTrials.gov code: NCT01970540. Date registration: 22 October, 2013.