TY - JOUR

T1 - Randomized phase III trial in extended stage small cell lung cancer comparing first line platinum in combination with etoposide or topotecan

AU - Mau-Sørensen, Morten

AU - Gerner-Rasmussen, Jonas

AU - Hansen, Olfred

AU - Holm, Bente

AU - Nyhus, Christa Haugaard

AU - McCulloch, Tine

AU - Nielsen, Henrik Anker

AU - Wedervang, Kim

AU - Rytter, Carsten

AU - Jeppesen, Nina

AU - Langer, Seppo W

PY - 2023

Y1 - 2023

N2 - Small cell lung cancer (SCLC) comprises 15% of newly diagnosed lung cancers with approximately two thirds of cases having extended stage (ES) at time of diagnosis [Citation1]. For the last four decades, progress in the treatment of ES SCLC has been limited. Recently, the addition of an immune checkpoint inhibitor to standard platin-based chemotherapy in fit patients has yielded a modest increase in median survival from approximately 10.3 to 13.0 months [Citation2,Citation3]. Hence, platinum-based chemotherapy in combination with etoposide remains the core of treatment of choice in the first line setting of ES SCLC. A meta-analysis published in 2000 showed that regimens containing cisplatin are superior to regimens without [Citation4]. Afterwards efforts were therefore made to develop agents to combine with cisplatin to improve outcome. The topoisomerase I inhibitor topotecan was identified as such an agent based on its efficacy in second line treatment of SCLC [Citation5,Citation6]. Initially, the combination yielded a high rate of fatal toxicity when cisplatin was administered on day 1 followed by 5 days of topotecan, but the regime became tolerable when cisplatin was administered on day 5 instead [Citation7–9]. Subsequently, a phase II study using a 3-day regimen with cisplatin administered on day 3 was compared to the 5-day regimen, which demonstrated similar response rates of 60% and 62%, respectively [Citation10]. The regimen has been further explored in a phase II trial, where the same sequence of cisplatin and topotecan was given to patients, but with a higher dose of topotecan. The study yielded an even higher overall response rate (ORR) of 72%, warranting further investigation [Citation11]. Accordingly, we initiated a multicentre randomized phase III study comparing topotecan/cisplatin with etoposide/carboplatin for ES SCLC, which we previously have reported [Citation12]. Platin-irinotecan is considered an equivalent option to platin-etoposide for the initial treatment of SCLC. The investigation of the closely related compound, topotecan, is particularly intriguing due to variations in metabolism (liver vs. renal) and toxicity (diarrhea and the cholinergic syndrome associated with irinotecan). Here, we present the final results of the trial with long-term follow-up.

AB - Small cell lung cancer (SCLC) comprises 15% of newly diagnosed lung cancers with approximately two thirds of cases having extended stage (ES) at time of diagnosis [Citation1]. For the last four decades, progress in the treatment of ES SCLC has been limited. Recently, the addition of an immune checkpoint inhibitor to standard platin-based chemotherapy in fit patients has yielded a modest increase in median survival from approximately 10.3 to 13.0 months [Citation2,Citation3]. Hence, platinum-based chemotherapy in combination with etoposide remains the core of treatment of choice in the first line setting of ES SCLC. A meta-analysis published in 2000 showed that regimens containing cisplatin are superior to regimens without [Citation4]. Afterwards efforts were therefore made to develop agents to combine with cisplatin to improve outcome. The topoisomerase I inhibitor topotecan was identified as such an agent based on its efficacy in second line treatment of SCLC [Citation5,Citation6]. Initially, the combination yielded a high rate of fatal toxicity when cisplatin was administered on day 1 followed by 5 days of topotecan, but the regime became tolerable when cisplatin was administered on day 5 instead [Citation7–9]. Subsequently, a phase II study using a 3-day regimen with cisplatin administered on day 3 was compared to the 5-day regimen, which demonstrated similar response rates of 60% and 62%, respectively [Citation10]. The regimen has been further explored in a phase II trial, where the same sequence of cisplatin and topotecan was given to patients, but with a higher dose of topotecan. The study yielded an even higher overall response rate (ORR) of 72%, warranting further investigation [Citation11]. Accordingly, we initiated a multicentre randomized phase III study comparing topotecan/cisplatin with etoposide/carboplatin for ES SCLC, which we previously have reported [Citation12]. Platin-irinotecan is considered an equivalent option to platin-etoposide for the initial treatment of SCLC. The investigation of the closely related compound, topotecan, is particularly intriguing due to variations in metabolism (liver vs. renal) and toxicity (diarrhea and the cholinergic syndrome associated with irinotecan). Here, we present the final results of the trial with long-term follow-up.

U2 - 10.1080/0284186X.2023.2278173

DO - 10.1080/0284186X.2023.2278173

M3 - Journal article

C2 - 37934081

VL - 62

SP - 1

EP - 4

JO - Acta Oncologica

JF - Acta Oncologica

SN - 1100-1704

IS - 12

ER -